Effects of Lycium barbarum polysaccharides on the proliferation and differentiation of primary Sertoli cells in young rats

Objective:Sertoli cells(SCs)provide physical support and material supply for germ cells and participate in the formation of blood-testis barrier.The number of SCs is directly proportional to the number of germ cells.And mature SCs ensure the growth of germ cells and the production of sperm.In this study,we explored the effect and underlying mechanism of Lycium barbarum polysaccharides(LBP)on primary SCs in young rats.Methods:Primary SCs were isolated from the testis of 20-day old rats.The cells were then treated with different concentrations of LBP.Immunocytochemistry was used to detect the expression of Ki67 and the androgen receptor(AR),and western blotting was used to detect the expression of cytokeratin-18(CK-18),AR and phosphorylated Akt(Ser473)in SCs.Results:The number of SCs increased significantly after LBP treatment,and the 100 mg/mL.LBP group had 14%more cells than the control group.The expression of Ki67 in LBP treated groups also increased significantly.LBP inhibited the expression of cytokeratin 18 in SCs.Besides,LBP increased the expression of AR on SCs and promoted the activation of Akt at the ser473 phosphorylation site.Conclusion:LBP promotes the proliferation of immature SCs in young rats and also accelerates their differentiation and maturation.This seems to be associated with activation of the Akt signaling pathway via up-regulation of AR.

IGIACP1 predicts the prognosis in multiple myeloma patients

Objective The aim of this study was to investigate the prognostic relevance of acid phosphatase 1(ACP1) expression in myeloma patients by using Gene Expression Omnibus(GEO) datasets.Methods A comprehensive search was performed in the GEO database in order to find appropriate datasets. The expression level of ACP1 was extracted from the dataset involving both newly diagnosed and relapsed myeloma patients, and a comparison was made. Clinical follow-up data and ACP1 expression were extracted, and survival analysis of overall survival was performed to compare the high-(top quartile) and low-expression(bottom quartile) groups. Analyses using Kaplan-Meier estimation, log-rank test, and restricted mean survival time(RMST) comparison were performed.Results The GSE 6477 dataset was used to make a comparison of the ACP1 expression levels among patients with newly diagnosed and relapsed myeloma. The ACP1 expression level was significantly higher in the relapsed group than in the newly diagnosed group [mean difference =-262.9, 95% confidence interval(CI) =(-420.2,-105.5), P = 0.002]. The GSE 2658 dataset was used for investigating the prognostic relevance of ACP1 expression in myeloma. The ACP1 high-expression group had a significantly worse prognosis [low vs high: hazard ratio = 0.54, 95% CI =(0.31, 0.95); χ2 = 5.02, log rank P = 0.0314]. The median survival was 55.9 months in the high-expression group and was not reached in the low-expression group. The restricted mean time loss(95% CI) was 11.03(12.97, 23.11) and 18.04(12.97, 23.11) for the low-and high-expression groups, respectively. The ratio of RMST(95% CI) between the two groups(high vs low) was 0.87(0.77, 0.99; P = 0.03).Conclusion Our study, for the first time, showed that ACP1 predicts the prognosis in multiple myeloma patients. Further studies are needed to determine the potential mechanism by which ACP1 is associated with clinical outcomes and should focus on the differential roles of low-molecular-weight protein tyrosine phosphatase(LMWPTP) isoforms.

Mitochondria Redistribution in Enterovirus A71 Infected Cells and Its Effect on Virus Replication

Enterovirus A71(EV-A71)is one of the main causative agents of hand,foot and mouth disease(HFMD)and it also causes severe neurologic complications in infected children.The interactions between some viruses and the host mitochondria are crucial for virus replication and pathogenicity.In this study,it was observed that EV-A71 infection resulted in a perinuclear redistribution of the mitochondria.The mitochondria rearrangement was found to require the microtubule network,the dynein complex and a low cytosolic calcium concentration.Subsequently,the EV-A71 non-structural protein 2BC was identified as the viral protein capable of inducing mitochondria clustering.The protein was found localized on mitochondria and interacted with the mitochondrial Rho GTPase 1(RHOT1)that is a key protein required for attachment between the mitochondria and the motor proteins,which are responsible for the control of mitochondria movement.Additionally,suppressing mitochondria clustering by treating cells with nocodazole,EHNA,thapsigargin or A23187 consistently inhibited EV?A71 replication,indicating that mitochondria recruitment played a crucial role in the EV-A71 life cycle.This study identified a novel function of the EV-A71 2BC protein and provided a potential model for the regulation of mitochondrial motility in EV-A71 infection.

Combined inhibition of Notch and FLT3 produces synergistic cytotoxic effects in FLT3/ITD^(+)acute myeloid leukemia

Internal tandem duplication(ITD)mutations of FMS-like tyrosine kinase-3(FLT3)are the most frequent genetic alterations in acute myeloid leukemia(AML)and predict a poor prognosis.FLT3 tyrosine kinase inhibitors(TKIs)provide short-term clinical responses,but the long-term prognosis of FLT3/ITD^(+)AML patients remains poor.Notch signaling is important in numerous types of tumors.However,the role of Notch signaling in FLT3/ITD^(+)AML remains to be elucidated.In the current study,we found that Notch signaling was activated upon FLT3-TKI treatment in FLT3/ITD^(+)cell lines and primary cells.As Notch signaling can be blocked byγ-secretase inhibitors(GSIs),we examined the combinatorial antitumor efficacy of FLT3-TKIs and GSIs against FLT3/ITD^(+)AML and explored the underlying molecular mechanisms.As a result,we observed synergistic cytotoxic effects,and the treatment preferentially reduced cell proliferation and induced apoptosis in FLT3/ITD^(+)AML cell lines and in primary AML cells.Furthermore,the combination of FLT3-TKI and GSI eradicated leukemic cells and prolonged survival in an FLT3/ITD^(+)patient-derived xenograft AML model.Mechanistically,differential expression analysis suggested that CXCR3 may be partially responsible for the observed synergy,possibly through ERK signaling.Our findings suggest that combined therapies of FLT3-TKIs with GSI may be exploited as a potential therapeutic strategy to treat FLT3/ITD^(+)AML.