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21.
Dai Sik Ko Junho Kang Hye Jin Heo Eun Kyoung Kim Kihun Kim Jin Mo Kang YunJae Jung Seung Eun Baek Yun Hak Kim 《International journal of biological sciences》2022,18(13):5154
Vascular smooth muscle cell (VSMC) proliferation is a hallmark of neointimal hyperplasia (NIH) in atherosclerosis and restenosis post-balloon angioplasty and stent insertion. Although numerous cytotoxic and cytostatic therapeutics have been developed to reduce NIH, it is improbable that a multifactorial disease can be successfully treated by focusing on a preconceived hypothesis. We, therefore, aimed to identify key molecules involved in NIH via a hypothesis-free approach. We analyzed four datasets (, GSE28829, GSE43292, and GSE100927), evaluated differentially expressed genes (DEGs) in wire-injured femoral arteries of mice, and determined their association with VSMC proliferation in vitro. Moreover, we performed RNA sequencing on platelet-derived growth factor (PDGF)-stimulated human VSMCs (hVSMCs) post-phosphoenolpyruvate carboxykinase 2 (PCK2) knockdown and investigated pathways associated with PCK2. Finally, we assessed NIH formation in Pck2 knockout (KO) mice by wire injury and identified PCK2 expression in human femoral artery atheroma. Among six DEGs, only PCK2 and RGS1 showed identical expression patterns between wire-injured femoral arteries of mice and gene expression datasets. PDGF-induced VSMC proliferation was attenuated when hVSMCs were transfected with PCK2 siRNA. RNA sequencing of PCK2 siRNA-treated hVSMCs revealed the involvement of the Akt-FoxO-PCK2 pathway in VSMC proliferation via Akt2, Akt3, FoxO1, and FoxO3. Additionally, NIH was attenuated in the wire-injured femoral artery of Pck2-KO mice and PCK2 was expressed in human femoral atheroma. PCK2 regulates VSMC proliferation in response to vascular injury via the Akt-FoxO-PCK2 pathway. Targeting PCK2, a downstream signaling mediator of VSMC proliferation, may be a novel therapeutic approach to modulate VSMC proliferation in atherosclerosis. GSE120521相似文献
22.
Kang SI Jin YJ Ko HC Choi SY Hwang JH Whang I Kim MH Shin HS Jeong HB Kim SJ 《Biochemical and biophysical research communications》2008,373(2):265-269
The anti-diabetic potential of Petalonia binghamiae extract (PBE) was evaluated in vivo. Dietary administration of PBE to streptozotocin (STZ)-induced diabetic mice significantly lowered blood glucose levels and improved glucose tolerance. The mode of action by which PBE attenuated diabetes was investigated in vitro using 3T3-L1 cells. PBE treatment stimulated 3T3-L1 adipocyte differentiation as evidenced by increased triglyceride accumulation. At the molecular level, peroxisome proliferator-activated receptor γ (PPARγ) and terminal marker protein aP2, as well as the mRNA of GLUT4 were up-regulated by PBE. In mature adipocytes, PBE significantly stimulated the uptake of glucose and the expression of insulin receptor substrate-1 (IRS-1). Furthermore, PBE increased PPARγ luciferase reporter gene activity in COS-1 cells. Taken together, these results suggest that the in vivo anti-diabetic effect of PBE is mediated by both insulin-like and insulin-sensitizing actions in adipocytes. 相似文献
23.
Joe Carver Domingos Ng Michelle Zhou Peggy Ko Dejin Zhan Mandy Yim David Shaw Brad Snedecor Michael W. Laird Steven Lang Amy Shen Zhilan Hu 《Biotechnology progress》2020,36(4):e2967
Historically, therapeutic protein production in Chinese hamster ovary (CHO) cells has been accomplished by random integration (RI) of expression plasmids into the host cell genome. More recently, the development of targeted integration (TI) host cells has allowed for recombination of plasmid DNA into a predetermined genomic locus, eliminating one contributor to clone-to-clone variability. In this study, a TI host capable of simultaneously integrating two plasmids at the same genomic site was used to assess the effect of antibody heavy chain and light chain gene dosage on antibody productivity. Our results showed that increasing antibody gene copy number can increase specific productivity, but with diminishing returns as more antibody genes are added to the same TI locus. Random integration of additional antibody DNA copies in to a targeted integration cell line showed a further increase in specific productivity, suggesting that targeting additional genomic sites for gene integration may be beneficial. Additionally, the position of antibody genes in the two plasmids was observed to have a strong effect on antibody expression level. These findings shed light on vector design to maximize production of conventional antibodies or tune expression for proper assembly of complex or bispecific antibodies in a TI system. 相似文献
24.
The antimicrobial properties of lignin by-products obtained by organic solvent, neutral sulfite semichemical and kraft pulping
were shown in a series of yeasts. Lignin can act as an inhibitor of growth ofSporobolomyces roseus, Candida tropicalis, Trichosporon cutaneum andCandida albicans. Oxidation of all lignin samples tested depresses their inhibitory effects. 相似文献
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26.
Eighty crossbred, multiparous sows, weighing between 190 and 320 kg, were randomly assigned to the following four treatment groups of 20 sows each: 1) saline-saline, 2) cloprostenol-saline, 3) saline-xylazine and 4) cloprostenol-xylazine. The mean gestation length of each multiparous sow was calculated. Cloprostenol (250 ug/sow, i.m.) or saline was given 3 d prior to the calculated due date at 11:30 a.m. Xylazine (2 mg/kg, i.m.) or saline was given 20 h after either the cloprostenol or previous saline treatment. Cloprostenol-xylazine treated sows had the shortest mean farrowing interval (1.5 +/- 0.3 h) when compared with the rest of the treatment groups (saline-saline:66.0 +/- 8.1, cloprostenol-saline:10.5 +/- 1.9, saline-xylazine:60.6 +/- 5.6 h). Farrowing time, percentage of stillbirths, average birth weight, d-5 and d-21 postbirth weights, number of pigs born, number of pigs born alive, and number of pigs surviving at 5 and 21 d afterbirth were not significantly different among the four groups. This study demonstrated that cloprostenol-xylazine treatment decreases the time to onset of farrowing with less variation than cloprostenol or xylazine alone. Therefore, the use of a cloprostenol-xylazine combination is suggested as an alternative method for inducing farrowing. 相似文献
27.
Yao-Li Chen Hui-Chuan Lin Kuo-Hua Lin Li-Si Lin Chia-En Hsieh Chih-Jan Ko Yu-Ju Hung Ping-Yi Lin 《PloS one》2015,10(3)
Background
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide and liver resection is the only potential curative treatment option for those patients. Postoperative complications specific to elderly surgical patients such as delirium will be increasingly relevant in the coming decades. Herein, we aimed to investigate the risk factors for postoperative delirium in patients who have received hepatectomy for HCC.Methods
This is a single medical center observational study and the study subjects comprised 401 individuals who underwent liver resection for hepatocellular carcinoma during January 2009 to October 2013. Multivariate analysis was used to examine whether preoperative, intra-operative, or postoperative variables were associated with the development of delirium.Results
Of the 401 patients who underwent hepatectomy, 34 developed postoperative delirium (8.4%). In the majority of those patients, symptoms and signs of the syndrome occurred on postoperative day 2 and the mean duration of symptoms was 3.61 ± 3.71 days. Multivariate analysis revealed that advanced age (>71 years) [odds ratio (OR) = 1.133, 95% confidence interval (CI): 1.071–1.200, p<0.001], prolonged operative time (>190 minutes) (OR = 1.009, 95% CI: 1.000–1.017, p = 0.038), a decreased postoperative hemoglobin level (< 10.16 g/dL) (OR = 0.777, 95% CI: 0.613–0.983, p = 0.036), and history of hypnotic drug use (OR = 3.074, 95% CI: 1.045–9.039, p = 0.041) were independent risk factors for the development of postoperative delirium after hepatectomy.Conclusions
Although the mechanism of postoperative delirium is not well understood, numbers of studies have shown that patients with postoperative delirium tend to have prolonged hospital stay, worse postoperative outcome and an increased risk of short- and long-term mortality. In this study, we found that advanced age, prolonged operative time, postoperative low hemoglobin level and history of hypnotic drug use are independent risk factors for postoperative delirium. 相似文献28.
Schenck HA Lenkowski PW Choudhury-Mukherjee I Ko SH Stables JP Patel MK Brown ML 《Bioorganic & medicinal chemistry》2004,12(5):979-993
Themisone, also known as Atrolactamide, was found, in the 1950s, to be a very potent anticonvulsant. It was hypothesized that the -CF(3) substitution would maintain the anticonvulsant activity. Anticonvulsant testing of our novel compounds by the National Institute of Health's Anticonvulsant Screening Project of the Antiepileptic Drug Discovery Program identified analogue 1, 3,3,3-trifluoro-2-hydroxy-2-phenyl-propionamide, to have potent anticonvulsant activity (MES ED(50) of 9.9 mg/kg, ScMET ED(50) of 34 mg/kg and TD(50) of 100 mg/kg). Therefore, a diverse range of analogues were synthesized utilizing multiple synthetic pathways to explore the structure-activity relationship. Patch clamp electrophysiology experiments demonstrate that compound 1 is an effective T-type calcium channel blocker. Altogether, these results suggest these compounds as a class of orally available anticonvulsants. 相似文献
29.
30.
Seung Jea Shin Kwang Jin Ko Tae Sun Kim Hyun Soo Ryoo Hyun Hwan Sung Hwang Gyun Jeon Byong Chang Jeong Seong Il Seo Hyun Moo Lee Han Yong Choi Seong Soo Jeon 《PloS one》2015,10(11)