Modulation of Growth and Transformation of Murine MC3T3-E1 Cell Line by Murine Wild-type and Mutant p53 Genes

We studied the effects of murine wild-type and mutant p53 genes (p53-wt and p53val135) on the growth and transformation of murine osteoblastoid cell line MC3T3-El. The mutant p53val135 enhanced focus formation of MC3T3-E1 cells by the activated H-ras plus LTR-myc gene and H-ras plus adenovirus 12 E1A gene more than four fold each, while p53-wt suppressed them 0.4 and 0.3 fold, respectively. The plating efficiency of hygromycin-resistant MC3T3-E1 cells after transfection of pSV2hygro were also increased by more than three fold with the cotransfection of p53val135 and the efficiency was also decreased 0.2 fold by cotransfection of p53-wt. These indicate that p53val135 enhances and p53-wt suppresses not only oncogene focus formation but also the cellular growth of the murine MC3T3-E1 cell line. Southern blot hybridization detected the tran-sfected p53-wt sequence only in three out of ten MC3T3-E1 cell lines established from foci induced by p53-wt and oncogenes, and failed to detect the p53-wt DNA in hygromycin-resistant MC3T3-E1 cell lines transfected with pSV2hygro and p53-wt. These suggest that MC3T3-E1 cells containing p53-wt are at a dis-advantage to form transformed foci or colonies, and suggests that MC3T3-E1 provides a good in vitro system to test the biological activity of murine wild-type and mutant p53 genes

Surgical site infection after total en bloc spondylectomy: Risk factors and the preventive new technology

Background context Surgical site infection (SSI) associated with instruments remains a serious and common complication in patients who undergo total en bloc spondylectomy (TES). It is very important that the risk factors for SSI are known to prevent it.Purpose The purpose of the study was to identify independent risk factors for SSI after TES and evaluate the positive effect of iodine-supported spinal instruments in the prevention of SSI after TES.Study design This is a retrospective clinical study.Patient sample One hundred twenty-five patients who underwent TES for vertebral tumor were evaluated.Outcome measures Incidence rate of SSI, risk factors for SSI after TES, and safety of iodine-supported spinal instruments were the outcome measures.Methods Risk factors for SSI were analyzed using logistic regression. In recent 69 patients with iodine-supported spinal instruments, the thyroid hormone levels in the blood were examined to confirm if iodine from the implant influenced thyroid function. Postoperative radiological evaluations were performed regularly.Results The rate of SSI was 6.4% (8/125 patients). By multivariate logistic regression, combined anterior and posterior approach and nonuse of iodine-supported spinal instruments were associated with an increased risk of SSI. The rate of SSI without iodine-supported spinal instruments was 12.5%, whereas the rate with iodine-supported spinal instruments was 1.4%. This difference was statistically significant. There were no detected abnormalities of thyroid gland function with the use of iodine-supported instruments. Among the 69 patients with iodine-supported spinal instruments, 2 patients required additional surgery because of instrument failure. However, there were no obvious involvements with the use of iodine-supported spinal instruments.Conclusions This study identified combined anterior and posterior approach and nonuse of iodine-supported spinal instruments to be independent risk factors for SSI after TES. Iodine-supported spinal instrument was extremely effective for prevention of SSI in patients with compromised status, and it had no detection of cytotoxic or adverse effects on the patients

Experimental and Numerical Study on Disc-RDE: Flow Structure and its Performances

The present study discusses disc-type rotating detonation engine (DRDE) experimentally and numerically. The experimental work shows that the detonation propagates in three different modes; single, dual, and hybrid. The operating frequency of dual-wave mode is 1.8-2.1 times faster than that of single wave mode. The number of detonation wave can be predicted based on the pressure history and the operating frequency signal. The numerical work shows the performance of 3D numerical analysis of DRDE with uniform injection case and multiport injection case. By increasing the wave number from one to two, the detonation propagation velocity decreases by 18.7 %. The one-detonation head case gives some better performance to the flow than the two-detonation head case. The inlet flow angle to the radial turbine becomes about 50 degrees to the radial direction no matter how large the plenum chamber is.AIAA Scitech 2021 Forum, 11–15 & 19–21 January, 2021, Virtual Even

Microsomal prostaglandin E synthase-1 in both cancer cells and hosts contributes to tumour growth, invasion and metastasis

mPGES-1 (microsomal prostaglandin E synthase-1) is a stimulus-inducible enzyme that functions downstream of COX (cyclo-oxygenase)-2 in the PGE2 (prostaglandin E2)-biosynthesis pathway. Although COX-2-derived PGE2 is known to play a role in the development of various tumours, the involvement of mPGES-1 in carcinogenesis has not yet been fully understood. In the present study, we used LLC (Lewis lung carcinoma) cells with mPGES-1 knockdown or overexpression, as well as mPGES-1-deficient mice to examine the roles of cancer cell- and host-associated mPGES-1 in the processes of tumorigenesis in vitro and in vivo. We found that siRNA (small interfering RNA) silencing of mPGES-1 in LLC cells decreased PGE2 synthesis markedly, accompanied by reduced cell proliferation, attenuated Matrigel™ invasiveness and increased extracellular matrix adhesion. Conversely, mPGES-1-overexpressing LLC cells showed increased proliferating and invasive capacities. When implanted subcutaneously into wild-type mice, mPGES-1-silenced cells formed smaller xenograft tumours than did control cells. Furthermore, LLC tumours grafted subcutaneously into mPGES-1-knockout mice grew more slowly than did those grafted into littermate wild-type mice, with concomitant decreases in the density of microvascular networks, the expression of pro-angiogenic vascular endothelial growth factor, and the activity of matrix metalloproteinase-2. Lung metastasis of intravenously injected LLC cells was also significantly less obvious in mPGES-1-null mice than in wild-type mice. Thus our present approaches provide unequivocal evidence for critical roles of the mPGES-1-dependent PGE2 biosynthetic pathway in both cancer cells and host microenvironments in tumour growth and metastasis

Determinants of cognitive performance and decline in 20 diverse ethno-regional groups: A COSMIC collaboration cohort study.

BACKGROUND: With no effective treatments for cognitive decline or dementia, improving the evidence base for modifiable risk factors is a research priority. This study investigated associations between risk factors and late-life cognitive decline on a global scale, including comparisons between ethno-regional groups. METHODS AND FINDINGS: We harmonized longitudinal data from 20 population-based cohorts from 15 countries over 5 continents, including 48,522 individuals (58.4% women) aged 54-105 (mean = 72.7) years and without dementia at baseline. Studies had 2-15 years of follow-up. The risk factors investigated were age, sex, education, alcohol consumption, anxiety, apolipoprotein E ε4 allele (APOE*4) status, atrial fibrillation, blood pressure and pulse pressure, body mass index, cardiovascular disease, depression, diabetes, self-rated health, high cholesterol, hypertension, peripheral vascular disease, physical activity, smoking, and history of stroke. Associations with risk factors were determined for a global cognitive composite outcome (memory, language, processing speed, and executive functioning tests) and Mini-Mental State Examination score. Individual participant data meta-analyses of multivariable linear mixed model results pooled across cohorts revealed that for at least 1 cognitive outcome, age (B = -0.1, SE = 0.01), APOE*4 carriage (B = -0.31, SE = 0.11), depression (B = -0.11, SE = 0.06), diabetes (B = -0.23, SE = 0.10), current smoking (B = -0.20, SE = 0.08), and history of stroke (B = -0.22, SE = 0.09) were independently associated with poorer cognitive performance (p < 0.05 for all), and higher levels of education (B = 0.12, SE = 0.02) and vigorous physical activity (B = 0.17, SE = 0.06) were associated with better performance (p < 0.01 for both). Age (B = -0.07, SE = 0.01), APOE*4 carriage (B = -0.41, SE = 0.18), and diabetes (B = -0.18, SE = 0.10) were independently associated with faster cognitive decline (p < 0.05 for all). Different effects between Asian people and white people included stronger associations for Asian people between ever smoking and poorer cognition (group by risk factor interaction: B = -0.24, SE = 0.12), and between diabetes and cognitive decline (B = -0.66, SE = 0.27; p < 0.05 for both). Limitations of our study include a loss or distortion of risk factor data with harmonization, and not investigating factors at midlife. CONCLUSIONS: These results suggest that education, smoking, physical activity, diabetes, and stroke are all modifiable factors associated with cognitive decline. If these factors are determined to be causal, controlling them could minimize worldwide levels of cognitive decline. However, any global prevention strategy may need to consider ethno-regional differences

Ischemic Preconditioning Effect of Prodromal Angina Is Attenuated in Acute Myocardial Infarction Patients With Hypertensive Left Ventricular Hypertrophy (前駆症状である狭心症の虚血性前処置効果は高血圧性左室肥大がある急性心筋梗塞患者では減弱する)

雑誌掲載版動物実験によると、急性心筋梗塞に対する虚血性前処置の保護効果は高血圧動物ではより著明と言われるが、臨床的にこれを検証した報告はない。本研究では再灌流治療に成功した初回前壁急性心筋梗塞(AMI)患者125例を高血圧の有無により2群に分け、更に各群を狭心症の前駆症状の有無により2群に分け、更に各群を狭心症の前駆症状の有無により2群に分けて再灌流治療後の左室形態と左室機能をSPECT、左室造影、心エコー図により評価した。その結果は動物実験とは逆で、高血圧性左室肥大があるAMI患者ではそれがないAMI患者と比較して前駆狭心症による保護効果は減弱していた