Yeast polyubiquitin gene UBI4 deficiency leads to early induction of apoptosis and shortened replicative lifespan.

Ubiquitin is a 76-amino acid protein that is highly conserved among higher and lower eukaryotes. The polyubiquitin gene UBI4 encodes a unique precursor protein that contains five ubiquitin repeats organized in a head-to-tail arrangement. Although the involvement of the yeast polyubiquitin gene UBI4 in the stress response was reported long ago, there are no reports regarding the underlying mechanism of this involvement. In this study, we used UBI4-deletion and UBI4-overexpressing yeast strains as models to explore the potential mechanism by which UBI4 protects yeast cells against paraquat-induced oxidative stress. Here, we show that ubi4Δ cells exhibit oxidative stress, an apoptotic phenotype, and a decreased replicative lifespan. Additionally, the reduced resistance of ubi4Δ cells to paraquat that was observed in this study was rescued by overexpression of either the catalase or the mitochondrial superoxide dismutase SOD2. We also demonstrated that only SOD2 overexpression restored the replicative lifespan of ubi4Δ cells. In contrast to the case of ubi4Δ cells, UBI4 overexpression in wild-type yeast increases the yeast's resistance to paraquat, and this overexpression is associated with large pools of expressed ubiquitin and increased levels of ubiquitinated proteins. Collectively, these findings highlight the role of the polyubiquitin gene UBI4 in apoptosis and implicate UBI4 as a modulator of the replicative lifespan.

CTT1 overexpression increases the replicative lifespan of MMS-sensitive Saccharomyces cerevisiae deficient in KSP1.

Ksplp is a nuclear-localized Ser/Thr kinase that is not essential for the vegetative growth of yeast. A global gene function analysis in yeast suggested that Ksplp was involved in the oxidative stress response; however, the underlying mechanism remains unclear. Here, we showed that KSP1-deficient yeast cells exhibit hypersensitivity to the DNA alkylating agent methyl methanesulphonate (MMS), and treatment of the KSP1-deficient strain with MMS could trigger abnormal mitochondrial membrane potential and up-regulate reactive oxygen species (ROS) production. In addition, the mRNA expression level of the catalase gene CTT1 (which encodes cytosolic catalase) and total catalase activity were strongly down-regulated in the KSP1-deleted strain compared with those in wild-type cells. Moreover, the KSP1 deficiency also leads to a shortened replicative lifespan, which could be restored by the increased expression of CTT1. On the other hand, KSP1-overexpressed (KSP1OX) yeast cells exhibited increased resistance towards MMS, an effect that was, at least in part, CTT1 independent. Collectively, these findings highlight the involvement of Ksplp in the DNA damage response and implicate Ksplp as a modulator of the replicative lifespan.

Laparoscopic Versus Open Colorectal Resection Within Fast Track Programs: An Update Meta-Analysis Based on Randomized Controlled Trials.

The objective of the study was to assess the safety and efficacy of laparoscopic colorectal surgery by comparing open operation within fast track (FT) programs. The Cochrane Library, PubMed, Embase and Chinese Biological Medicine Database were searched to identify all available randomized controlled trials (RCTs) comparing laparoscopic with open colorectal resection within FT programs. A total of seven RCTs were finally included, enrolling 714 patients with colorectal cancer: 373 patients underwent laparoscopic surgery and FT programs (laparoscopic/FT group) and 341 patients received open operation and FT programs (open/FT group). Postoperative hospital stay (weighted mean difference (WMD): 0.66; 95% CI: 0.27 - 1.04; P < 0.05), total hospital stay (WMD: 1.46; 95% CI: 0.40 - 2.51; P < 0.05) and overall complications (RR: 1.31; 95% CI: 1.12 - 1.54; P < 0.05) were significantly lower in laparoscopic/FT group than in open/FT group. However, no statistically significant differences on mortality (risk ratio (RR): 2.26; 95% CI: 0.62 - 8.22; P = 0.21), overall surgical complications (RR: 1.19; 95% CI: 0.94 - 1.51; P = 0.15) and readmission rates (RR: 1.33; 95% CI: 0.79 - 2.22; P = 0.28) were found between both groups. The laparoscopic colorectal surgery combined with FT programs shows high-level evidence on shortening postoperative and total hospital stay, reducing overall complications without compromising patients' safety.

The role of omega-3 fatty acids in acute pancreatitis: a meta-analysis of randomized controlled trials.

To determine whether treatment with omega-3 fatty acids (ω-3 FA) provides benefits to patients with acute pancreatitis (AP). The Cochrane Library, PubMed, Embase, Web of Science, and Chinese Biomedical Literature Database were searched. Data analysis was performed using Revman 5.2 software. A total of eight randomized controlled trials (RCTs) were included. Overall, ω-3 FA treatment resulted in a significantly reduced risk of mortality (RR 0.35; 95% CI 0.16 to 0.75, p < 0.05), infectious complications (RR 0.54; 95% CI 0.34 to 0.85, p < 0.05) and length of hospital stay (MD -6.50; 95% CI -9.54 to -3.46, p < 0.05), but not length of ICU stay (MD -1.98; 95% CI -6.92 to 2.96, p > 0.05). In subgroup analysis, only patients who received ω-3 FA parenterally had some statistically significant benefits in terms of mortality (risk ratio (RR) 0.37; 95% confidence interval (CI) 0.16 to 0.86, p < 0.05), infectious complications (RR 0.5; 95% CI 0.28 to 0.9, p < 0.05) and length of hospital stay (mean difference (MD) -8.13; 95% CI -10.39 to -5.87, p < 0.001). The administration of ω-3 FA may be beneficial for decreasing mortality, infectious complications, and length of hospital stay in AP, especially when used parenterally. Large and rigorously designed RCTs are required to elucidate the efficacy of parenteral or enteral ω-3 FA treatment in AP.

CIA2 deficiency results in impaired oxidative stress response and enhanced intracellular basal UPR activity in Saccharomyces cerevisiae.

Yeast Cia2p is a component of the cytosolic Fe/S protein assembly (CIA) machinery. Initial studies of the CIA machinery were performed in yeast, but the precise role of Cia2p in this eukaryote is still unknown. We report that CIA2 deficiency results in impaired oxidative stress response, as evidenced by increased sensitivity to the oxidant cumene hydroperoxide (CHP), impaired activities of superoxide dismutases and aconitase and decreased replicative lifespan in the mutants. Moreover, intracellular reactive oxygen species levels were significantly increased in CIA2-deficient cells after treatment with CHP. We also show that CIA2-deficient cells display an increased resistance to tunicamycin-induced endoplasmic reticulum (ER) stress, as evidenced by the upregulated splicing of the mRNA of HAC1, which encodes a functional transcription factor that regulates the transcription of unfolded protein response (UPR) target genes, suggesting enhanced intracellular UPR activity. Furthermore, the transcription of several canonical UPR target genes is strongly induced in CIA2-deficient cells as compared with wild-type controls. Taken together, these results suggest the involvement of Cia2p in oxidative and ER stress responses in yeast.