AIM: To investigate and clarify the intervention mechanism of trigonelline(TRG)in preventing ferroptosis in ARPE-19 cells based on the Nrf2/HO-1/GPX4 pathway.METHODS: The ARPE-19 cells were cultured and subsequently treated with varying concentrations of trigonelline to ascertain the most effective concentration for modulating the cells. Then the cells were categorized into distinct groups, including normal control(NC)group, high glucose(HG)group, Fer-1 group, TRG group based on the determined concentration. Samples from each group were then gathered to assess relevant indicators. The intracellular levels of glutathione(GSH), malondialdehyde(MDA), and Ferrion were quantified in accordance with the protocols provided by the GSH, MDA, and Ferrion detection kits. Flow cytometry was employed to measure the ROS levels within each group. Additionally, Western blot analysis was conducted to examine the expression of nuclear factor erythroid 2-related factor 2(Nrf2), heme oxygenase-1(HO-1), glutathione peroxidase(GPX4), and acyl-CoA synthetase long-chain family member 4(ACSL4)across the different groups.RESULTS: The preconditioning intervention with 40 μg/mL TRG effectively mitigated the decline in cell activity induced by high glucose levels. The levels of reactive oxygen species(ROS)and MDA in the HG group were markedly elevated compared to the NC group; and the TRG group exhibited significantly reduced levels of ROS and MDA compared to those of the HG group, with the antioxidant stress index GSH showing opposite trends to those of ROS and MDA across all the groups. Whereas the Fer-1 and TRG groups showed decreased expression levels of ACSL4 protein and iron ions, and the expression levels of Nrf2, HO-1 and GPX4 in the Fer-1 and TRG groups were increased.CONCLUSION: TRG protects ARPE-19 cells from the detrimental effects of high glucose by targeting the Nrf2/HO-1/GPX4 signaling pathway to counter ferroptosis.

Chronic, unresolved inflammation correlates with persistent hepatic injury and fibrosis, ultimately progressing to hepatocellular carcinoma (HCC). Bisdemethoxycurcumin (BDMC) demonstrates therapeutic potential against HCC, yet its mechanism in preventing hepatic "inflammation-carcinoma transformation" remains incompletely understood. In the current research, clinical HCC specimens underwent analysis using hematoxylin-eosin (H&E) staining and immunohistochemistry (IHC) to evaluate the expression of fibrosis markers, M2 macrophage markers, and CXCL12. In vitro, transforming growth factor-β1 (TGF-β1)-induced LX-2 cells and a co-culture system of LX-2, THP-1, and HCC cells were established. Cell functions underwent assessment through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, and Transwell assays. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blotting and immunofluorescence evaluated the differential expression of molecules. The interaction between β-catenin/TCF4 and CXCL12 was examined using co-immunoprecipitation (Co-IP), dual luciferase, and chromatin immunoprecipitation (ChIP) assays. A DEN-induced rat model was developed to investigate BDMC's role in liver fibrosis-associated HCC (LFAHCC) development in vivo. Our results showed that clinical HCC tissues exhibited elevated fibrosis and enriched M2 macrophages. BDMC delayed liver fibrosis progression to HCC in vivo. BDMC inhibited the inflammatory microenvironment induced by activated hepatic stellate cells (HSCs). Furthermore, BDMC suppressed M2 macrophage-induced fibrosis and HCC cell proliferation and metastasis. Mechanistically, BDMC repressed TCF4/β-catenin complex formation, thereby reducing CXCL12 transcription in LX-2 cells. Moreover, CXCL12 overexpression reversed BDMC's inhibitory effect on macrophage M2 polarization and its mediation of fibrosis, as well as HCC proliferation and metastasis. BDMC significantly suppressed LFAHCC development through CXCL12 in rats. In conclusion, BDMC inhibited LFAHCC progression by reducing M2 macrophage polarization through suppressing β-catenin/TCF4-mediated CXCL12 transcription.
Animals ; Liver Neoplasms/etiology* ; Humans ; Carcinoma, Hepatocellular/immunology* ; Liver Cirrhosis/complications* ; Macrophages/drug effects* ; Male ; Rats ; Chemokine CXCL12/genetics* ; Diarylheptanoids/pharmacology* ; Rats, Sprague-Dawley ; beta Catenin/genetics*

Objective:To evaluate the efficacy and safety of albumin bound paclitaxel(nab-PTX)and solvent based paclitaxel(sb-PTX)in neoadjuvant chemotherapy(NACT)for advanced epithelial ovarian cancer(EOC).Methods:A retrospective analysis was conducted on the clinical data of 107 patients with advanced EOC who un-derwent preoperative NACT in the First Affiliated Hospital of Xi'an Jiaotong University from June 11,2018 to Sep-tember 19,2023.Among them,52 patients were treated with nab-PTX combined with carboplatin intravenous chemotherapy(nab-PTX group),and 55 with sb-PTX combined with carboplatin intravenous chemotherapy(sb-PTX group).The clinical indicators after NACT,intraoperative conditions of cytoreductive surgery and ad-verse events during the NACT were compared in two groups.Results:The maximum tumor diameter(3.7 cm vs.3.8 cm),CA125(28.9 U/ml vs.31.6 U/ml)and HE4(102.5 U/ml vs.119.0 U/ml)levels in the nab PTX group after NACT were significantly lower than those in the sb-PTX group,and the differences were statistically significant(P＜0.001).After NACT,the total input(2580 ml vs.2100 ml),the proportion of surgical complexity score(36.54％vs.18.18％),and lymph node resection rate(57.69％vs.29.09％)in the nab-PTX group were significantly higher than those in the sb-PTX group(P＜0.05).There was no statistically significant difference(P＞0.05)in the amount of ascites,clinical efficacy evaluation,ORR,DCR,surgical time,intraoperative bleeding,total output,postoperative hospital stays,surgical satisfaction,pathological complete response rate(pCR),transfu-sion of blood products,lymph node metastasis and adverse effects during NACT between the two groups.Con-clusions:Nab-PTX has a better clinical disease control effect than sb-PTX in NACT,in order to achieve better cy-toreductive surgery,but it has no significant effect on pathological remission.The safety of the two drugs is similar.

Objective:To evaluate the efficacy and safety of albumin bound paclitaxel(nab-PTX)and solvent based paclitaxel(sb-PTX)in neoadjuvant chemotherapy(NACT)for advanced epithelial ovarian cancer(EOC).Methods:A retrospective analysis was conducted on the clinical data of 107 patients with advanced EOC who un-derwent preoperative NACT in the First Affiliated Hospital of Xi'an Jiaotong University from June 11,2018 to Sep-tember 19,2023.Among them,52 patients were treated with nab-PTX combined with carboplatin intravenous chemotherapy(nab-PTX group),and 55 with sb-PTX combined with carboplatin intravenous chemotherapy(sb-PTX group).The clinical indicators after NACT,intraoperative conditions of cytoreductive surgery and ad-verse events during the NACT were compared in two groups.Results:The maximum tumor diameter(3.7 cm vs.3.8 cm),CA125(28.9 U/ml vs.31.6 U/ml)and HE4(102.5 U/ml vs.119.0 U/ml)levels in the nab PTX group after NACT were significantly lower than those in the sb-PTX group,and the differences were statistically significant(P＜0.001).After NACT,the total input(2580 ml vs.2100 ml),the proportion of surgical complexity score(36.54％vs.18.18％),and lymph node resection rate(57.69％vs.29.09％)in the nab-PTX group were significantly higher than those in the sb-PTX group(P＜0.05).There was no statistically significant difference(P＞0.05)in the amount of ascites,clinical efficacy evaluation,ORR,DCR,surgical time,intraoperative bleeding,total output,postoperative hospital stays,surgical satisfaction,pathological complete response rate(pCR),transfu-sion of blood products,lymph node metastasis and adverse effects during NACT between the two groups.Con-clusions:Nab-PTX has a better clinical disease control effect than sb-PTX in NACT,in order to achieve better cy-toreductive surgery,but it has no significant effect on pathological remission.The safety of the two drugs is similar.

Objective:To evaluate the efficacy and safety of albumin bound paclitaxel(nab-PTX)and solvent based paclitaxel(sb-PTX)in neoadjuvant chemotherapy(NACT)for advanced epithelial ovarian cancer(EOC).Methods:A retrospective analysis was conducted on the clinical data of 107 patients with advanced EOC who un-derwent preoperative NACT in the First Affiliated Hospital of Xi'an Jiaotong University from June 11,2018 to Sep-tember 19,2023.Among them,52 patients were treated with nab-PTX combined with carboplatin intravenous chemotherapy(nab-PTX group),and 55 with sb-PTX combined with carboplatin intravenous chemotherapy(sb-PTX group).The clinical indicators after NACT,intraoperative conditions of cytoreductive surgery and ad-verse events during the NACT were compared in two groups.Results:The maximum tumor diameter(3.7 cm vs.3.8 cm),CA125(28.9 U/ml vs.31.6 U/ml)and HE4(102.5 U/ml vs.119.0 U/ml)levels in the nab PTX group after NACT were significantly lower than those in the sb-PTX group,and the differences were statistically significant(P＜0.001).After NACT,the total input(2580 ml vs.2100 ml),the proportion of surgical complexity score(36.54％vs.18.18％),and lymph node resection rate(57.69％vs.29.09％)in the nab-PTX group were significantly higher than those in the sb-PTX group(P＜0.05).There was no statistically significant difference(P＞0.05)in the amount of ascites,clinical efficacy evaluation,ORR,DCR,surgical time,intraoperative bleeding,total output,postoperative hospital stays,surgical satisfaction,pathological complete response rate(pCR),transfu-sion of blood products,lymph node metastasis and adverse effects during NACT between the two groups.Con-clusions:Nab-PTX has a better clinical disease control effect than sb-PTX in NACT,in order to achieve better cy-toreductive surgery,but it has no significant effect on pathological remission.The safety of the two drugs is similar.

Objective:To evaluate the efficacy and safety of albumin bound paclitaxel(nab-PTX)and solvent based paclitaxel(sb-PTX)in neoadjuvant chemotherapy(NACT)for advanced epithelial ovarian cancer(EOC).Methods:A retrospective analysis was conducted on the clinical data of 107 patients with advanced EOC who un-derwent preoperative NACT in the First Affiliated Hospital of Xi'an Jiaotong University from June 11,2018 to Sep-tember 19,2023.Among them,52 patients were treated with nab-PTX combined with carboplatin intravenous chemotherapy(nab-PTX group),and 55 with sb-PTX combined with carboplatin intravenous chemotherapy(sb-PTX group).The clinical indicators after NACT,intraoperative conditions of cytoreductive surgery and ad-verse events during the NACT were compared in two groups.Results:The maximum tumor diameter(3.7 cm vs.3.8 cm),CA125(28.9 U/ml vs.31.6 U/ml)and HE4(102.5 U/ml vs.119.0 U/ml)levels in the nab PTX group after NACT were significantly lower than those in the sb-PTX group,and the differences were statistically significant(P＜0.001).After NACT,the total input(2580 ml vs.2100 ml),the proportion of surgical complexity score(36.54％vs.18.18％),and lymph node resection rate(57.69％vs.29.09％)in the nab-PTX group were significantly higher than those in the sb-PTX group(P＜0.05).There was no statistically significant difference(P＞0.05)in the amount of ascites,clinical efficacy evaluation,ORR,DCR,surgical time,intraoperative bleeding,total output,postoperative hospital stays,surgical satisfaction,pathological complete response rate(pCR),transfu-sion of blood products,lymph node metastasis and adverse effects during NACT between the two groups.Con-clusions:Nab-PTX has a better clinical disease control effect than sb-PTX in NACT,in order to achieve better cy-toreductive surgery,but it has no significant effect on pathological remission.The safety of the two drugs is similar.

Objective:To evaluate the efficacy and safety of albumin bound paclitaxel(nab-PTX)and solvent based paclitaxel(sb-PTX)in neoadjuvant chemotherapy(NACT)for advanced epithelial ovarian cancer(EOC).Methods:A retrospective analysis was conducted on the clinical data of 107 patients with advanced EOC who un-derwent preoperative NACT in the First Affiliated Hospital of Xi'an Jiaotong University from June 11,2018 to Sep-tember 19,2023.Among them,52 patients were treated with nab-PTX combined with carboplatin intravenous chemotherapy(nab-PTX group),and 55 with sb-PTX combined with carboplatin intravenous chemotherapy(sb-PTX group).The clinical indicators after NACT,intraoperative conditions of cytoreductive surgery and ad-verse events during the NACT were compared in two groups.Results:The maximum tumor diameter(3.7 cm vs.3.8 cm),CA125(28.9 U/ml vs.31.6 U/ml)and HE4(102.5 U/ml vs.119.0 U/ml)levels in the nab PTX group after NACT were significantly lower than those in the sb-PTX group,and the differences were statistically significant(P＜0.001).After NACT,the total input(2580 ml vs.2100 ml),the proportion of surgical complexity score(36.54％vs.18.18％),and lymph node resection rate(57.69％vs.29.09％)in the nab-PTX group were significantly higher than those in the sb-PTX group(P＜0.05).There was no statistically significant difference(P＞0.05)in the amount of ascites,clinical efficacy evaluation,ORR,DCR,surgical time,intraoperative bleeding,total output,postoperative hospital stays,surgical satisfaction,pathological complete response rate(pCR),transfu-sion of blood products,lymph node metastasis and adverse effects during NACT between the two groups.Con-clusions:Nab-PTX has a better clinical disease control effect than sb-PTX in NACT,in order to achieve better cy-toreductive surgery,but it has no significant effect on pathological remission.The safety of the two drugs is similar.

Objective:To evaluate the efficacy and safety of albumin bound paclitaxel(nab-PTX)and solvent based paclitaxel(sb-PTX)in neoadjuvant chemotherapy(NACT)for advanced epithelial ovarian cancer(EOC).Methods:A retrospective analysis was conducted on the clinical data of 107 patients with advanced EOC who un-derwent preoperative NACT in the First Affiliated Hospital of Xi'an Jiaotong University from June 11,2018 to Sep-tember 19,2023.Among them,52 patients were treated with nab-PTX combined with carboplatin intravenous chemotherapy(nab-PTX group),and 55 with sb-PTX combined with carboplatin intravenous chemotherapy(sb-PTX group).The clinical indicators after NACT,intraoperative conditions of cytoreductive surgery and ad-verse events during the NACT were compared in two groups.Results:The maximum tumor diameter(3.7 cm vs.3.8 cm),CA125(28.9 U/ml vs.31.6 U/ml)and HE4(102.5 U/ml vs.119.0 U/ml)levels in the nab PTX group after NACT were significantly lower than those in the sb-PTX group,and the differences were statistically significant(P＜0.001).After NACT,the total input(2580 ml vs.2100 ml),the proportion of surgical complexity score(36.54％vs.18.18％),and lymph node resection rate(57.69％vs.29.09％)in the nab-PTX group were significantly higher than those in the sb-PTX group(P＜0.05).There was no statistically significant difference(P＞0.05)in the amount of ascites,clinical efficacy evaluation,ORR,DCR,surgical time,intraoperative bleeding,total output,postoperative hospital stays,surgical satisfaction,pathological complete response rate(pCR),transfu-sion of blood products,lymph node metastasis and adverse effects during NACT between the two groups.Con-clusions:Nab-PTX has a better clinical disease control effect than sb-PTX in NACT,in order to achieve better cy-toreductive surgery,but it has no significant effect on pathological remission.The safety of the two drugs is similar.

Objective:To evaluate the efficacy and safety of albumin bound paclitaxel(nab-PTX)and solvent based paclitaxel(sb-PTX)in neoadjuvant chemotherapy(NACT)for advanced epithelial ovarian cancer(EOC).Methods:A retrospective analysis was conducted on the clinical data of 107 patients with advanced EOC who un-derwent preoperative NACT in the First Affiliated Hospital of Xi'an Jiaotong University from June 11,2018 to Sep-tember 19,2023.Among them,52 patients were treated with nab-PTX combined with carboplatin intravenous chemotherapy(nab-PTX group),and 55 with sb-PTX combined with carboplatin intravenous chemotherapy(sb-PTX group).The clinical indicators after NACT,intraoperative conditions of cytoreductive surgery and ad-verse events during the NACT were compared in two groups.Results:The maximum tumor diameter(3.7 cm vs.3.8 cm),CA125(28.9 U/ml vs.31.6 U/ml)and HE4(102.5 U/ml vs.119.0 U/ml)levels in the nab PTX group after NACT were significantly lower than those in the sb-PTX group,and the differences were statistically significant(P＜0.001).After NACT,the total input(2580 ml vs.2100 ml),the proportion of surgical complexity score(36.54％vs.18.18％),and lymph node resection rate(57.69％vs.29.09％)in the nab-PTX group were significantly higher than those in the sb-PTX group(P＜0.05).There was no statistically significant difference(P＞0.05)in the amount of ascites,clinical efficacy evaluation,ORR,DCR,surgical time,intraoperative bleeding,total output,postoperative hospital stays,surgical satisfaction,pathological complete response rate(pCR),transfu-sion of blood products,lymph node metastasis and adverse effects during NACT between the two groups.Con-clusions:Nab-PTX has a better clinical disease control effect than sb-PTX in NACT,in order to achieve better cy-toreductive surgery,but it has no significant effect on pathological remission.The safety of the two drugs is similar.

Objective:To evaluate the efficacy and safety of albumin bound paclitaxel(nab-PTX)and solvent based paclitaxel(sb-PTX)in neoadjuvant chemotherapy(NACT)for advanced epithelial ovarian cancer(EOC).Methods:A retrospective analysis was conducted on the clinical data of 107 patients with advanced EOC who un-derwent preoperative NACT in the First Affiliated Hospital of Xi'an Jiaotong University from June 11,2018 to Sep-tember 19,2023.Among them,52 patients were treated with nab-PTX combined with carboplatin intravenous chemotherapy(nab-PTX group),and 55 with sb-PTX combined with carboplatin intravenous chemotherapy(sb-PTX group).The clinical indicators after NACT,intraoperative conditions of cytoreductive surgery and ad-verse events during the NACT were compared in two groups.Results:The maximum tumor diameter(3.7 cm vs.3.8 cm),CA125(28.9 U/ml vs.31.6 U/ml)and HE4(102.5 U/ml vs.119.0 U/ml)levels in the nab PTX group after NACT were significantly lower than those in the sb-PTX group,and the differences were statistically significant(P＜0.001).After NACT,the total input(2580 ml vs.2100 ml),the proportion of surgical complexity score(36.54％vs.18.18％),and lymph node resection rate(57.69％vs.29.09％)in the nab-PTX group were significantly higher than those in the sb-PTX group(P＜0.05).There was no statistically significant difference(P＞0.05)in the amount of ascites,clinical efficacy evaluation,ORR,DCR,surgical time,intraoperative bleeding,total output,postoperative hospital stays,surgical satisfaction,pathological complete response rate(pCR),transfu-sion of blood products,lymph node metastasis and adverse effects during NACT between the two groups.Con-clusions:Nab-PTX has a better clinical disease control effect than sb-PTX in NACT,in order to achieve better cy-toreductive surgery,but it has no significant effect on pathological remission.The safety of the two drugs is similar.