1.Latest developments in hepatocyte transplantation
International Journal of Surgery 2014;41(8):556-561
Hepatocyte transplantation is an additional effective treatment for liver failure subsequent to liver transplantation.It can also be used to as a bridge to orthotopic liver transplantation for patients with acute liver failure.Compared with liver transplantation,hepatocyte transplantation is less invasive and rejective.However,the development of both treatment is impeded by the shortage of organ donors.The quality and quantity of the liver cells and their routes of transplantation should be the substantial factors if hepatocyte transplantation is to be a treatment extended to large numbers of patients.This review discusses the latest bench-to-bedside developments in hepatocyte transplantation with the aim of drawing the attention of our domestic colleagues.
2.Therapeutic effect analysis of plasma exchange therapy on rhabdomyolysis syndrome patients caused by wasp stings
Jirui TANG ; Hansong BAI ; Li JING ; Jing HOU
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2019;26(4):406-408
Objective To investigate the efficacy of plasma exchange therapy in the treatment of rhabdomyolysis syndrome (RMS) caused by wasp stings. Methods Sixty patients with RMS caused by wasp stings were enrolled in the Poisoning Treatment Ward of the Affiliated Hospital of Southwest Medical University from January 2015 to June 2019, including 40 patients complicated with acute kidney injury (AKI). After admission, the patients were given local treatment and systemic medication (intravenous infusion of glucocorticoid, calcium gluconate injection, intramuscular injection of isopropazine hydrochloride and other antihistamines). Plasma exchange was performed on the first and second day after admission, and according to the renal function situations, the patients with AKI underwent intermittent hemodialysis. The changes of urea (Ur), creatinine (Cr), hypersensitive troponin T (hs-TnT), myoglobin (MYO), creatine kinase isoenzyme (CK-MB), lactic dehydrogenase (LDH) and pathological changes of kidney were monitored on admission and after twice of plasma exchanges, and the above results of indexes were compared and analyzed. Results With the prolongation of the plasma exchange time, after the first plasma exchange the level of hs-TnT was significantly higher than that before the plasma exchange [μg/L: 1.30 (0.16, 4.37) vs. 0.26 (0.06, 1.26)], and the levels of LDH and CK-MB were lower than those before the exchange [LDH (μmol·s-1·L-1): 14.01 (6.73, 31.52) vs. 20.55 (8.73, 42.46), CK-MB (U/L): 41.25 (21.27, 102.83) vs. 89.92 (35.85, 163.53), both P < 0.05]; after the second plasma exchange, the Ur, Cr, LDH, hs-TnT, MYO and CK-MB were decreased significantly compared with those before the exchange [Ur (mmol/L): 9.77 (6.43, 11.90) vs. 11.58 (7.65, 19.49), Cr (μmol/L): 90.35 (67.10, 336.10) vs. 115.25 (77.50, 288.83), LDH (μmol·s-1·L-1): 7.84 (5.14, 18.68) vs 20.55 (8.73, 42.46), hs-TnT (μg/L): 0.02 (0.01, 0.09) vs. 0.26 (0.06, 1.26), MYO (μg/L): 200.00 (70.39, 1 000.00) vs. >1 000.00 (1 000.00, >1 000.00), CK-MB (U/L): 4.34 (1.86, 23.65) vs. 89.92 (35.85, 163.56), all P < 0.05]. Under light microscope, renal tubular epithelial cells fell off and showed"naked membrane", and infiltration of a small amount of inflammatory cells could be seen. Conclusion Plasma exchange can effectively remove macromolecules such as MYO, hs-TnT, CK-MB and LDH, reduce acute renal damage caused by rhabdomyolysis syndrome, shorten the course of disease and decrease mortality.
3.Ginsenoside Rg5 enhances the radiosensitivity of lung adenocarcinoma via reducing HSP90-CDC37 interaction and promoting client protein degradation
Hansong BAI ; Jiahua LYU ; Xinyu NIE ; Hao KUANG ; Long LIANG ; Hongyuan JIA ; Shijie ZHOU ; Churong LI ; Tao LI
Journal of Pharmaceutical Analysis 2023;13(11):1296-1308
Ginsenoside Rg5 is a rare ginsenoside showing promising tumor-suppressive effects.This study aimed to explore its radio-sensitizing effects and the underlying mechanisms.Human lung adenocarcinoma cell lines A549 and Calu-3 were used for in vitro and in vivo analysis.Bioinformatic molecular docking prediction and following validation by surface plasmon resonance(SPR)technology,cellular thermal shift assay(CETSA),and isothermal titration calorimetry(ITC)were conducted to explore the binding between ginsenoside Rg5 and 90 kD heat shock protein alpha(HSP90α).The effects of ginsenoside Rg5 on HSP90-cell division cycle 37(CDC37)interaction,the client protein stability,and the downstream regulations were further explored.Results showed that ginsenoside Rg5 could induce cell-cycle arrest at the G1 phase and enhance irradiation-induced cell apoptosis.It could bind to HSP90α with a high affinity,but the affinity was drastically decreased by HSP90α Y61A mutation.Co-immunoprecipitation(Co-IP)and ITC assays confirmed that ginsenoside Rg5 disrupts the HSP90-CDC37 interaction in a dose-dependent manner.It reduced irradiation-induced upre-gulation of the HSP90-CDC37 client proteins,including SRC,CDK4,RAF1,and ULK1 in A549 cell-derived xenograft(CDX)tumors.Ginsenoside Rg5 or MRT67307(an IKKe/TBK1 inhibitor)pretreatment suppressed irradiation-induced elevation of the LC3-Ⅱ/β ratio and restored irradiation-induced downregulation of p62 expression.In A549 CDX tumors,ginsenoside Rg5 treatment suppressed LC3 expression and enhanced irradiation-induced DNA damage.In conclusion,ginsenoside Rg5 may be a potential radiosensitizer for lung adenocarcinoma.It interacts with HSP90α and reduces the binding between HSP90 and CDC37,thereby increasing the ubiquitin-mediated proteasomal degradation of the HSP90-CDC37 client proteins.