Objective:To observe the effect of nuclear transcription factor- κB(NF- κB) on cerebral edema in rats with traumatic brain injury(TBI).Methods:Male SD rau with fluid percussion injury(FPI) were selected.After separa...Objective:To observe the effect of nuclear transcription factor- κB(NF- κB) on cerebral edema in rats with traumatic brain injury(TBI).Methods:Male SD rau with fluid percussion injury(FPI) were selected.After separation and culture,rats' astrocytes all suffered FPL The expression of NF-κB and the water content were detected at the animal and cellular levels,while the activity of NOX was evaluated at the cellular level.Results:According to the results,the positive expression of NF-κB and expression of mRNA were significantly increased and the water content was increased for rats after TBI.while NF-κB inhibitor BAY 11-7082 could significantly reduce the effect of TBI.1 and 3h after FPI of astrocytes,the activation of NFkB was incrcased and BAY 11-7082 could significantly improve the injury-induced swelling of astrocytes.After the injury of astrocytes,the activity of NOX was also increased,while BAY11-7082 could reduce the activity of NOX.Conclusions:The results show that the activation of NF- κB in astrocytes is a key factor in the process of cerebral edema after TBI of rats.展开更多
Colorectal cancer (CRC) is a prevalent malignant tumor often leading to liver metastasis and mortality. Despite some success with PD-1/PD-L1 immunotherapy, the response rate for colon cancer patients remains relativel...Colorectal cancer (CRC) is a prevalent malignant tumor often leading to liver metastasis and mortality. Despite some success with PD-1/PD-L1 immunotherapy, the response rate for colon cancer patients remains relatively low. This is closely related to the immunosuppressive tumor microenvironment mediated by tumor-associated macrophages (TAMs). Our previous work identified that a phosphoglycerate mutase 1 (PGAM1) allosteric inhibitor, HKB99, exerts a range of anti-tumor activities in lung cancer. Here, we found that upregulation of PGAM1 correlates with increased levels of M2-like tumor-associated macrophages (TAMs) in human colon cancer samples, particularly in liver metastatic tissues. HKB99 suppressed tumor growth and metastasis in cell culture and syngeneic tumor models. M2-polarization, induced by colon cancer cell co-culture, was reversed by HKB99. Conversely, the increased migration of colon cancer cells by M2-TAMs was remarkably restrained by HKB99. Notably, a decrease in TAM infiltration was required for the HKB99-mediated anti-tumor effect, along with an increase in CD8^(+) T cell infiltration. Moreover, HKB99 improved the efficacy of anti-PD-1 treatment in syngeneic tumors. Overall, this study highlights HKB99's inhibitory activity in TAM-mediated colon cancer progression. Targeting PGAM1 could lead to novel therapeutic strategies and enhance the effectiveness of existing immunotherapies for colon cancer.展开更多
基金supported by Technology Program for Development of Pharmacy of Shandong 2013(No.2013WS0351)
文摘Objective:To observe the effect of nuclear transcription factor- κB(NF- κB) on cerebral edema in rats with traumatic brain injury(TBI).Methods:Male SD rau with fluid percussion injury(FPI) were selected.After separation and culture,rats' astrocytes all suffered FPL The expression of NF-κB and the water content were detected at the animal and cellular levels,while the activity of NOX was evaluated at the cellular level.Results:According to the results,the positive expression of NF-κB and expression of mRNA were significantly increased and the water content was increased for rats after TBI.while NF-κB inhibitor BAY 11-7082 could significantly reduce the effect of TBI.1 and 3h after FPI of astrocytes,the activation of NFkB was incrcased and BAY 11-7082 could significantly improve the injury-induced swelling of astrocytes.After the injury of astrocytes,the activity of NOX was also increased,while BAY11-7082 could reduce the activity of NOX.Conclusions:The results show that the activation of NF- κB in astrocytes is a key factor in the process of cerebral edema after TBI of rats.
基金National Natural Science Foundation of China(82073868)Science and Technology Commission of Shanghai Municipality(20S11900100 and 21TQ016,China)China Postdoctoral Science Foundation(2022M722138).
文摘Colorectal cancer (CRC) is a prevalent malignant tumor often leading to liver metastasis and mortality. Despite some success with PD-1/PD-L1 immunotherapy, the response rate for colon cancer patients remains relatively low. This is closely related to the immunosuppressive tumor microenvironment mediated by tumor-associated macrophages (TAMs). Our previous work identified that a phosphoglycerate mutase 1 (PGAM1) allosteric inhibitor, HKB99, exerts a range of anti-tumor activities in lung cancer. Here, we found that upregulation of PGAM1 correlates with increased levels of M2-like tumor-associated macrophages (TAMs) in human colon cancer samples, particularly in liver metastatic tissues. HKB99 suppressed tumor growth and metastasis in cell culture and syngeneic tumor models. M2-polarization, induced by colon cancer cell co-culture, was reversed by HKB99. Conversely, the increased migration of colon cancer cells by M2-TAMs was remarkably restrained by HKB99. Notably, a decrease in TAM infiltration was required for the HKB99-mediated anti-tumor effect, along with an increase in CD8^(+) T cell infiltration. Moreover, HKB99 improved the efficacy of anti-PD-1 treatment in syngeneic tumors. Overall, this study highlights HKB99's inhibitory activity in TAM-mediated colon cancer progression. Targeting PGAM1 could lead to novel therapeutic strategies and enhance the effectiveness of existing immunotherapies for colon cancer.
