Cancer multidrug resistance (MDR) impairs the therapeutic efficacy of various chemotherapeutics. Novel approaches, particularly the development of MDR reversal agents, are critically needed to address this challenge. This study demonstrates that tenacissoside I (TI), a compound isolated from Marsdenia tenacissima (Roxb.) Wight et Arn, traditionally used in clinical practice as an ethnic medicine for cancer treatment, exhibits significant MDR reversal effects in ABCB1-mediated MDR cancer cells. TI reversed the resistance of SW620/AD300 and KBV200 cells to doxorubicin (DOX) and paclitaxel (PAC) by downregulating ABCB1 expression and reducing ABCB1 drug transport function. Mechanistically, protein arginine methyltransferase 1 (PRMT1), whose expression correlates with poor prognosis and shows positive association with both ABCB1 and EGFR expressions in tumor tissues, was differentially expressed in TI-treated SW620/AD300 cells. SW620/AD300 and KBV200 cells exhibited elevated levels of EGFR asymmetric dimethylarginine (aDMA) and enhanced PRMT1-EGFR interaction compared to their parental cells. Moreover, TI-induced PRMT1 downregulation impaired PRMT1-mediated aDMA of EGFR, PRMT1-EGFR interaction, and EGFR downstream signaling in SW620/AD300 and KBV200 cells. These effects were significantly reversed by PRMT1 overexpression. Additionally, TI demonstrated resistance reversal to PAC in xenograft models without detectable toxicities. This study establishes TI's MDR reversal effect in ABCB1-mediated MDR human cancer cells through inhibition of PRMT1-mediated aDMA of EGFR, suggesting TI's potential as an MDR modulator for improving chemotherapy outcomes.
Humans ; Protein-Arginine N-Methyltransferases/antagonists & inhibitors* ; Drug Resistance, Neoplasm/drug effects* ; ErbB Receptors/genetics* ; Animals ; Cell Line, Tumor ; Drug Resistance, Multiple/drug effects* ; Methylation/drug effects* ; Saponins/administration & dosage* ; Mice ; Mice, Nude ; Mice, Inbred BALB C ; ATP Binding Cassette Transporter, Subfamily B/genetics* ; Doxorubicin/pharmacology* ; Paclitaxel/pharmacology* ; Female ; Repressor Proteins

Metabolic syndrome (MetS) represents a clinical syndrome composed of a series of risk factors for cardiovascular and cerebrovascular diseases.Emerging evidence highlights the multifaceted therapeutic potential of sodium-glucose cotransporter 2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) beyond their established glucose-lowering efficacy, with recent studies demonstrating their remarkable ability to improve multiple metabolic parameters, including blood pressure reduction, weight loss, and cardiorenal function enhancement, suggesting a pivotal role in improving MetS-related risk factors.The elderly population represents a high-risk cohort for metabolic disorders.Nevertheless, conventional medications are associated with problems such as an elevated risk of hypoglycaemia and insufficient protection of multiple vital organs, including the heart and kidneys.This review expounds on the impacts of SGLT-2i and GLP-1RAs on elderly patients with MetS and their potential mechanisms of action, providing reference value for optimizing the management of metabolism-related diseases in the elderly.

Metabolic syndrome (MetS) represents a clinical syndrome composed of a series of risk factors for cardiovascular and cerebrovascular diseases.Emerging evidence highlights the multifaceted therapeutic potential of sodium-glucose cotransporter 2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) beyond their established glucose-lowering efficacy, with recent studies demonstrating their remarkable ability to improve multiple metabolic parameters, including blood pressure reduction, weight loss, and cardiorenal function enhancement, suggesting a pivotal role in improving MetS-related risk factors.The elderly population represents a high-risk cohort for metabolic disorders.Nevertheless, conventional medications are associated with problems such as an elevated risk of hypoglycaemia and insufficient protection of multiple vital organs, including the heart and kidneys.This review expounds on the impacts of SGLT-2i and GLP-1RAs on elderly patients with MetS and their potential mechanisms of action, providing reference value for optimizing the management of metabolism-related diseases in the elderly.

This study was performed to investigate the features of HBV-specific CD8+T cell reactivity in patients with chronic hepatitis B(CHB),HBV-induced liver cirrhosis(LC)or hepatocellular carcinoma(HCC).A total of 124 CHB patients,36 LC patients,and 114 HCC patients were enrolled in this study.The reactive HBV-specific CD8+T cells in peripheral blood were enumerated using an innovative ELISPOT system.In addition,19 CHB patients and 20 HCC patients were longitudinally monitored with an interval of 3-5 months.Data showed that the numbers of reactive HBV-specific CD8+T cells in CHB group were not significantly different from that in LC group,but obviously lower than that in HCC group(P=0.009 9),especially HBsAg-,HBpol-and HBe/cAg-specific CD8+T cells.In CHB group,the patients with normal ALT level,AST level,or low HBV-DNA load showed significantly more reactive HBV-specific CD8+T cells than the patients with abnormal ALT level,abnormal AST level,or high HBV-DNA load.Furthermore,the duration of NUCs treatment had an impact on the HBV-specific CD8+T cell reactivity in CHB patients,while different NUCs at the same treatment duration did not bring different reactivity of HBV-specific T cells.In LC group,the HBeAg-positive patients presented much more reactive HBV-specific CD8+T cells than the HBeAg-negative patients did.In HCC group,the numbers of reactive HBV-specific CD8+T cells in the patients with normal AFP level or normal DCP level were significantly higher than that in the patients with abnormal AFP level or abnormal DCP level.Longitudinal monitoring results showed that HBV-specific CD8+T cell reactivity displayed a slow upward trend in the CHB patients undergoing NUCs treatment,and an obvious increasing in the HCC patients undergoing combined treatment of targeted drugs and immunotherapy.Taken together,the features of HBV-specific CD8+T cell reactivity are distinct among the CHB,LC and HCC patients,and are influenced by virological indicators,tumor markers and treatment regimens.Therefore,more attention should be paid to the changes of HBV-specific CD8+T cell reactivity during clinical treatment.

IFN-gamma and TNF-alpha were co-coupled to the polystyrene cell culture plate by the photo-immobilization method. To investigate the synergistic effect of IFN-gamma and TNF-alpha on the HeLa cells, HeLa cells were treated with co-coupled cytokine or non-coupled cytokine in a time course in this study. The morphology detection, cell cycle analysis by flow cytometry, phosphatidyl serine analysis and capase-3 activity detection demonstrated that the two kinds of treatments both induce HeLa cells apoptosis. Non-coupled cytokine worked more quickly while co-coupled cytokine kept more permanent effect. The caspase-3 activity assay indicated that the caspase-3 activity of HeLa cells treated with non-coupled cytokine is higher than that of HeLa cells treated with co-coupled cytokine. This may imply that co-coupled cytokine not only induces the caspase-dependent pathway, but also induces the caspase-independent pathway.
Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Drug Synergism ; HeLa Cells ; Humans ; Immobilized Proteins ; pharmacology ; Interferon-gamma ; pharmacology ; Tumor Necrosis Factor-alpha ; pharmacology