117 research outputs found
Glutathione Peroxidase 3 Delivered by hiPSC-MSCs Ameliorated Hepatic IR Injury via Inhibition of Hepatic Senescence
Background and Aims: Down-regulation of GPx3 accelerated hepatic senescence, which further caused overwhelming inflammation and severe liver graft injury. MSCs derived from human induced pluripotent stem cells (hiPSC-MSCs) have been developed as more efficient delivery vehicle with the property of injury tropism. Here, we aimed to explore the suppressive role of GPx3 in hepatic IR injury using novel delivery system of hiPSC-MSCs. Methods: The mice IR injury model with partial hepatectomy was established. The engineered hiPSC-MSCs delivering GPx3 was constructed. All the mice were segregated into three groups. hiPSC-MSC-GPx3, hiPSC-MSC-pCDH (vector control) or PBS were injected via portal vein after reperfusion. Liver injury was evaluated by histological and serological test. Hepatic apoptosis was detected by Tunel staining and remnant liver regeneration was assessed by Ki67 staining. The role of hepatic senescence in liver graft injury was evaluated in rat orthotopic liver transplantation model. The suppressive effect of GPx3 on hepatic senescence was examined in mice IR injury model and confirmed in vitro. Hepatic senescence was detected by SA-Ξ²-Gal and P16/ink4a staining. Results: GPx3 can be successfully delivered by hiPSC-MSCs into liver tissues. Histological examination showed that hiPSC-MSC-GPx3 treatment significantly ameliorated hepatic IR injury post-operation. Significantly lower LDH (891.43Β±98.45 mU/mL, P<0.05) and AST (305.77Β±36.22 IU/L, P<0.01) were observed in hiPSC-MSC-GPx3 group compared with control groups. Less apoptotic hepatocytes were observed and the remnant liver regeneration was more active in hiPSC-MSC-GPx3 group. In rat orthotopic liver transplantation model, more senescent hepatocytes were observed in small-for-size liver graft, in which GPx3 expression was significantly compromised. In mice IR injury model, hiPSC-MSC-GPx3 significantly suppressed hepatic senescence. In addition, rGPx3 inhibited cellular senescence of liver cells in a dose dependent manner. Four candidate genes (CD44, Nox4, IFNG, SERPERINB2) were identified to be responsible for suppressive effect of GPx3 on hepatic senescence. Conclusion: Engineered hiPSC-MSCs delivering GPx3 ameliorated hepatic IR injury via inhibition of hepatic senescence.published_or_final_versio
Observation of a ppb mass threshoud enhancement in \psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p}) decay
The decay channel
is studied using a sample of events collected
by the BESIII experiment at BEPCII. A strong enhancement at threshold is
observed in the invariant mass spectrum. The enhancement can be fit
with an -wave Breit-Wigner resonance function with a resulting peak mass of
and a
narrow width that is at the 90% confidence level.
These results are consistent with published BESII results. These mass and width
values do not match with those of any known meson resonance.Comment: 5 pages, 3 figures, submitted to Chinese Physics
Checkpoint Signaling, Base Excision Repair, and PARP Promote Survival of Colon Cancer Cells Treated with 5-Fluorodeoxyuridine but Not 5-Fluorouracil
The fluoropyrimidines 5-fluorouracil (5-FU) and FdUrd (5-fluorodeoxyuridine; floxuridine) are the backbone of chemotherapy regimens for colon cancer and other tumors. Despite their widespread use, it remains unclear how these agents kill tumor cells. Here, we have analyzed the checkpoint and DNA repair pathways that affect colon tumor responses to 5-FU and FdUrd. These studies demonstrate that both FdUrd and 5-FU activate the ATR and ATM checkpoint signaling pathways, indicating that they cause genotoxic damage. Notably, however, depletion of ATM or ATR does not sensitize colon cancer cells to 5-FU, whereas these checkpoint pathways promote the survival of cells treated with FdUrd, suggesting that FdUrd exerts cytotoxicity by disrupting DNA replication and/or inducing DNA damage, whereas 5-FU does not. We also found that disabling the base excision (BER) repair pathway by depleting XRCC1 or APE1 sensitized colon cancer cells to FdUrd but not 5-FU. Consistent with a role for the BER pathway, we show that small molecule poly(ADP-ribose) polymerase 1/2 (PARP) inhibitors, AZD2281 and ABT-888, remarkably sensitized both mismatch repair (MMR)-proficient and -deficient colon cancer cell lines to FdUrd but not to 5-FU. Taken together, these studies demonstrate that the roles of genotoxin-induced checkpoint signaling and DNA repair differ significantly for these agents and also suggest a novel approach to colon cancer therapy in which FdUrd is combined with a small molecule PARP inhibitor
Measurement of the matrix element for the decay Ξ·β²βΞ·Ο +Ο -
The Dalitz plot of Ξ·ββ²βΞ·Οβ+Οβ- decay is studied using (225.2Β±2.8)Γ106 J/Ο events collected with the BESIII detector at the BEPCII eβ+eβ- collider. With the largest sample of Ξ·ββ² decays to date, the parameters of the Dalitz plot are determined in a generalized and a linear representation. Also, the branching fraction of J/ΟβΞ³Ξ·ββ² is determined to be (4.84Β±0.03Β±0.24)Γ10β-3, where the first error is statistical and the second systematic. Β© 2011 American Physical Society.published_or_final_versio
First observation of the decays ΟcJβΟ0Ο0Ο0Ο0
We present a study of the P-wave spin-triplet charmonium Ο cJ decays (J=0, 1, 2) into Ο0Ο0Ο0Ο0. The analysis is based on 106Γ106 Οββ² decays recorded with the BESIII detector at the BEPCII electron positron collider. The decay into the Ο0Ο0Ο0Ο0 hadronic final state is observed for the first time. We measure the branching fractions B(Ο c0βΟ0Ο0Ο0Ο0)=(3.34Β±0. 06Β±0.44)Γ10β-3, B(Ο c1βΟ0Ο0Ο0Ο0) =(0.57Β±0.03Β±0.08)Γ10β-3, and B(Ο c2βΟ0Ο0Ο0Ο0)=(1.21Β±0.05Β±0.16) Γ10β-3, where the uncertainties are statistical and systematical, respectively. Β© 2011 American Physical Society.published_or_final_versio
Branching fraction measurements of Οc0 and Οc2 to Ο0Ο0 and Ξ·Ξ·
Using a sample of 1.06Γ108 Ο β² decays collected by the BESIII detector, Οc0 and Οc2 decays into Ο0Ο0 and Ξ·Ξ· are studied. The branching fraction results are Br(Οc0βΟ 0Ο0)=(3.23Β±0.03Β±0.23Β±0.14)Γ10 -3, Br(Οc2βΟ0Ο0)=(8.8Β±0.2Β±0.6Β±0.4)Γ10 -4, Br(Οc0βΞ·Ξ·)=(3.44Β±0.10Β±0. 24Β±0.2)Γ10 -3, and Br(Οc2βΞ·Ξ·)=(6. 5Β±0.4Β±0.5Β±0.3)Γ10 -4, where the uncertainties are statistical, systematic due to this measurement, and systematic due to the branching fractions of Ο β²β Ξ³ΟcJ. The results provide information on the decay mechanism of Οc states into pseudoscalars. Β© 2010 The American Physical Society.published_or_final_versio
Study of a00(980)-f0(980) mixing
Using samples of 2.25Γ108 J/Ο events and 1.06Γ108 Ο β² events collected with the BES III detector, we study the f 0(980)βa00(980) and a00(980)βf 0(980) transitions in the processes J/ΟβΟf 0(980) βΟa00(980) and Ο c1βΟ0a00(980)βΟ0f 0(980), respectively. Evidence for f 0(980)βa00(980) is found with a significance of 3.4Ο, while in the case of a00(980)βf 0(980) transition, the significance is 1.9Ο. Measurements and upper limits of both branching ratios and mixing intensities are determined. Β© 2011 American Physical Society.published_or_final_versio
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