Latest Issue
Issue 6 ， 2018
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PGC-1α coordinates with Bcl-2 to control the cell cycle in U251 cells through reducing ROS#
Abstract：B-cell lymphoma 2 (Bcl-2) has a dual function, acting as both an oncogene and an anti-tumor gene. It is well known that Bcl-2 exerts its tumor promoting function through the mitochondrial pathway. However, the mechanism by which it suppresses tumor formation is not well understood. We have previously shown that Bcl-2 inhibits cell cycle progression from the G0/G1 to the S phase after serum starvation, and that quiescent Bcl-2 expressing cells maintain a significantly lower level of mitochondrial reactive oxygen species (ROS) than control cells. Based on the fact that ROS mediate cell cycle progression and are controlled by peroxisome proliferator-activated receptor-γ co-activator 1α (PGC-1α), a key molecule induced by prolonged starvation and involved in mitochondrial metabolism, we hypothesized that PGC-1α might be related to the cell cycle function of Bcl-2. In this paper, we show that PGC-1α is upregulated by Bcl-2 overexpression and downregulated following Bcl-2 knockdown or downregulation after serum starvation. However, Bcl-2 is negatively regulated by PGC-1α expression. Further, co-immunoprecipitation (co-IP) experiments showed that PGC-1α protein is co-precipitated with Bcl-2 at the G0/G1 phase. Taken together, our results suggest that PGC-1α interacts with Bcl-2 after serum depletion, and that Bcl-2 might recruit PGC-1α to reduce ROS, which in turn delays cell cycle progression in coordination with Bcl-2.Keywords：B-cell lymphoma 2 (Bcl-2);Peroxisome proliferator-activated receptor-γ;co-activator 1α;(PGC-1α);Mitochondria;Reactive oxygen species (ROS);Cell cycle- 112
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Published：2022-01-05 -
NF-κB in mitochondria regulates PC12 cell apoptosis following lipopolysaccharide-induced injury
Abstract：Objective:To determine the relationship between nuclear transcription factor κB (NF-κB) expression in mitochondria and neuronal cell apoptosis after lipopolysaccharide (LPS)-induced injury.Methods:The effect of drug administration on PC12 cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and Hoechst 33342 staining. The morphology and function of mitochondria were investigated with electron microscopy and rhodamine 123, respectively. The activity of adenine nucleotide translocase 1 (ANT1), lipid peroxide, and anti-peroxidase enzymes was measured by enzyme-linked immunosorbent assay (ELISA). Relative expression levels of NF-κB were measured by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting.Results:Pyrrolidine dithiocarbamate (PDTC, an NF-κB inhibitor) and nerve growth factor (NGF) not only reduced apoptosis but also had a protective effect on mitochondrial structure and function in a PC12 cell LPS damage model. The subcellular distribution of NF-κB demonstrated that NGF, diterpene acid atractyloside (ATR, an ANT1 antagonist), and PDTC alleviated increases in mitochondrial NF-κB after LPS-induced injury.Conclusions:(1) NF-κB is activated in mitochondria via uptake of ANT1 during apoptosis following LPS-induced injury in neuronal cells; (2) NGF not only decreases the activity of NF-κB but also reduces ANT1 activity, which in turn decreases NF-κB levels in mitochondria and suppresses mitochondria-mediated apoptosis.Keywords：Nuclear transcription factorκ;B (NF-κ;B);Mitochondria;Apoptosis;Adenine nucleotide translocase 1 (ANT1);Lipopolysaccharide (LPS)- 114
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Published：2022-01-05 -
Protection of plasma transfusion against lipopolysaccharide/D-galactosamine-induced fulminant hepatic failure through inhibiting apoptosis of hepatic cells in mice
Abstract：Fulminant hepatic failure is a severe clinical condition associated with extremely poor outcomes and high mortality. A number of studies have demonstrated the ability of plasma transfusion to successfully treat fulminant hepatic failure, but the underlying mechanisms are not well understood. The aim of the present study is to define the mechanisms of plasma transfusion treatment in lipopolysaccharide/D-galactosamine (LPS/D-GalN)-induced mice. LPS/D-GalN treatment in mice causes significant hepatic failure, including increasing serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, histopathological changes in centrilobular necrosis and inflammatory cells, and the up-regulation of inflammation (tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)). When LPS/D-GaIN-induced mice were treated with plasma, these changes were halted. Results showed that plasma transfusion significantly reduced mortality, and decreased the levels of AST, ALT, and inflammation factors such as TNF-α and IL-6. The expression levels of cleaved Caspase-3, BAX, and p53 were down-regulated and Bcl-2 was up-regulated, suggesting that plasma can reduce LPS/D-GalN-induced apoptosis. The protective mechanism of plasma against LPS/D-GalN-induced fulminant hepatic failure is related to the inhibition of the inflammatory response and the reduction in apoptosis through the down-regulation of the p53-induced apoptotic pathway.Keywords：Fulminant hepatic failure;Plasma;Inflammation;Apoptosis- 27
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Published：2022-01-05 -
Alteration of
SlYABBY2b gene expression impairs tomato ovary locule number and endogenous gibberellin content#Abstract：Tomato is an ideal model species for fleshy fruit development research. SlYABBY2b regulates the ovary locule number, which is increased by gibberellins, in tomato. However, the relationship between SlYABBY2b and endogenous gibberellin is poorly understood. In this study, SlYABBY2b-overexpressing and RNA interference (RNAi) transgenic tomato plants were used to elucidate the mechanism by which SlYABBY2b regulates the ovary locule number and endogenous gibberellin content in tomato. SlYABBY2b-overexpressing plants showed fewer locules and lower gibberellin content than the control plants. Contrasting results were found in the RNAi lines. Therefore, the SlYABBY2b gene negatively regulates tomato ovary locule number and endogenous gibberellin content. Furthermore, the expression of SlYABBY2b gene was remarkably higher than that of the wild type in the apical shoots of gibberellin-deficient mutants. This showed that the gibberellins can inhibit the expression of SlYABBY2b gene negative regulation. Further study revealed that SlYABBY2b suppressed the expression of SlGA20ox1 and SlGA3ox2, but increased that of SlGA2ox1 and SlGA2ox5 in the apical shoots of SlYABBY2b-overexpressing plants, thereby reducing gibberellin content. Contrasting results were found in the RNAi lines. Our results showed that the SlYABBY2b gene was located on gibberellin signal transduction pathways, fed back regulation of the synthesis of gibberellin, and felt exogenous gibberellin signal to further regulate the formation of tomato locule.Keywords：SlYABBY2b;Gibberellin;Gibberellin-deficient mutants;Ovary locule number;Transgenic plant;Gene expression;Tomato- 102
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Published：2022-01-05 -
Proteomic analysis of human umbilical vein endothelial cells exposed to PM2.5
Abstract：Exposure to fine ambient particulate matter (PM2.5) is known to be associated with cardiovascular disease. To uncover the molecular mechanisms involved in cardiovascular toxicity of PM2.5, we investigated alterations in the protein profile of human umbilical vein endothelial cells (HUVECs) treated with PM2.5 using two-dimensional electrophoresis in conjunction with mass spectrometry (MS). A total of 31 protein spots were selected as differentially expressed proteins and identified by matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) MS. The results demonstrated that DNA damage and cell apoptosis are important factors contributing to PM2.5-mediated toxicity in HUVECs. It is further proposed that PM2.5 can inhibit superoxide dismutase (SOD) activity and increase reactive oxygen species (ROS) and malonaldehyde (MDA) production in a concentration-dependent manner. Induction of apoptosis and DNA damage through oxidative stress pathways may be one of the key toxicological events occurring in HUVECs under PM2.5 stress. These results indicated that the toxic mechanisms of PM2.5 on cardiovascular disease are related to endothelial dysfunction.Keywords：Fine ambient particulate matter (PM2.5);Human umbilical vein endothelial cell (HUVEC);Proteomics;Toxic mechanism- 26
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Published：2022-01-05 -
Pharmacokinetic comparison of gossypol isomers in cattle: transfer from diet to plasma and degradation by rumen microbes#
Abstract：A pharmacokinetic comparison of gossypol isomers in cattle was made by investigating their transfer from ingested food to plasma and their degradation by rumen microbes. The gossypol isomers in whole cottonseed, plasma, and rumen fluid were determined by high-performance liquid chromatography (HPLC). The intakes of (+)-and (−)-gossypol by cows on three farms were about 5.6–8.5 and 3.8–5.9 g/(d·herd), respectively. The plasma gossypol concentrations increased as ingestion increased and ranged from 0.31 to 0.48 μg/ml for the (+) form and from 0.39 to 0.59 μg/ml for the (−) form. The (+) form was slightly predominant (58.8%–59.8%) in the gossypol ingested by the cows, whereas the (−) form predominated (54.6%–55.9%) in the plasma. An in vitro study showed that at 6 h, 67.4% and 85.7% of the (−)-gossypol were degraded in 500 and 1000 μg/g treatment groups, respectively, and these increased to 83.6% and 92.5%, respectively, at 12 h. The regularity of the degradation of (+)-gossypol was similar to that of (−)-gossypol. These results showed that (−)-gossypol may be more persistent than (+)-gossypol in plasma, and that the degradation of the gossypol isomers in the rumen is rapid and not enantioselective in cattle.Keywords：Pharmacokinetics;Gossypol isomers;Cattle- 21
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Published：2022-01-05 -
Outcomes of EC-MPS combined with low-dose tacrolimus in DCD kidney transplantation for high-risk DGF recipients
Abstract：Effective use of immunosuppressive agents to avoid the occurrence of nephrotoxicity and rejection in recipients with delayed graft function (DGF) is a concern for physicians. We investigated the outcomes of treatment with enteric-coated mycophenolate sodium (EC-MPS) in combination with a low-dose of tacrolimus (Tac) in renal transplantation for recipients with a high risk of DGF. We conducted a retrospective study of 61 recipients with a high risk of DGF who were treated with EC-MPS and low-dose Tac. The recipients were separated into a no-DGF group and a DGF group, based on whether DGF actually occurred. The results showed that although EC-MPS and Tac doses were similar in both groups, the percentage of recipients whose mycophenolic acid area under the curve 0–12 h (MPA-AUC0–12 h) was below 30 (mg·h)/L was significantly higher and the Tac trough concentration significantly lower in the DGF group one week after transplantation. Notably, a higher incidence of biopsy-proven acute rejection (BPAR) was found in the DGF group and among all recipients whose MPA-AUC0–12 h was less than 30 (mg·h)/L at one week after transplantation. One-year graft survival, patient survival, allograft function, and the incidence of the most common adverse events were similar in the two groups. In conclusion, the immunosuppressive regime is applicable to Chinese kidney transplant recipients, and early low exposure to EC-MPS was related to acute rejection in the recipients at a high risk of DGF.Keywords：Enteric-coated mycophenolate sodium (EC-MPS);Tacrolimus;Delayed graft function (DGF);Donation after cardiac death (DCD);Kidney transplantation- 18
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Published：2022-01-05 -
Effects of body mass index on the outcomes of in vitro fertilization in Chinese patients with polycystic ovary syndrome: a retrospective cohort study
Abstract：Objective:To investigate the effects of body mass index (BMI) on the outcomes of in vitro fertilization (IVF) in Chinese patients with polycystic ovary syndrome (PCOS).Methods:In the retrospective cohort study, a total of 1074 patients with PCOS undergoing IVF between April 2010 and May 2017 in two reproductive medicine centers, respectively in eastern China (Women’s Hospital, School of Medicine, Zhejiang University, Zhejiang Province) and in southern China (Maternal and Child Health Care Hospital of Liuzhou, Guangxi Province), were included. The patients were divided into four groups according to the recommended Chinese BMI cut-off points: underweight (BMI<18.5 kg/m2), normal weight (18.5 kg/m2≤BMI<24.0 kg/m2), overweight (24.0 kg/m2≤BMI<28.0 kg/m2), and obese (BMI≥28.0 kg/m2). The basic characteristics of the PCOS patients, the details of IVF treatment, and the pregnancy outcomes were collected.Mainresults:There were no significant differences among the normal weight, overweight, and obese PCOS patients undergoing IVF on the biochemical pregnancy rate, clinical pregnancy rate, miscarriage rate, live birth rate, or term delivery rate (P>0.05), although the overweight and obese PCOS patients required more gonadotropin (Gn) (P<0.001) as well as longer stimulation period (P<0.001), and got less retrieved oocytes (P<0.05) and fertilized oocytes (P<0.05). The underweight PCOS patients required less Gn (P<0.05) and achieved higher live birth rate and term delivery rate (P<0.05), compared with the normal weight PCOS patients.Conclusions:High BMI had no negative effects on the outcomes of IVF in Chinese patients with PCOS; however, the conclusion may seem a little limited due to the retrospective design and the potential bias.Keywords：Body mass index;In vitro fertilization;Polycystic ovary syndrome- 17
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Published：2022-01-05
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