Re-Expression of AKAP12 Inhibits Progression and Metastasis Potential of Colorectal Carcinoma In Vivo and In Vitro

Background: AKAP12/Gravin (A kinase anchor protein 12) is one of the A-kinase scaffold proteins and a potential tumor suppressor gene in human primary cancers. Our recent study demonstrated the highly recurrent loss of AKAP12 in colorectal cancer and AKAP12 reexpression inhibited proliferation and anchorage-independent growth in colorectal cancer cells, implicating AKAP12 in colorectal cancer pathogenesis. Methods: To evaluate the effect of this gene on the progression and metastasis of colorectal cancer, we examined the impact of overexpressing AKAP12 in the AKAP12-negative human colorectal cancer cell line LoVo, the single clone (LoVo-AKAP12) compared to mock-transfected cells (LoVo-CON). Results: pCMV6-AKAP12-mediated AKAP12 re-expression induced apoptosis (3 % to 12.7%, p,0.01), migration (89.667.5 cells to 31.064.1 cells, p,0.01) and invasion (82.765.2 cells to 24.763.3 cells, p,0.01) of LoVo cells in vitro compared to control cells. Nude mice injected with LoVo-AKAP12 cells had both significantly reduced tumor volume (p,0.01) and increased apoptosis compared to mice given AKAP12-CON. The quantitative human-specific Alu PCR analysis showed overexpression of AKAP12 suppressed the number of intravasated cells in vivo (p,0.01). Conclusion: These results demonstrate that AKAP12 may play an important role in tumor growth suppression and the survival of human colorectal cancer

Role of p53 in pseudorabies virus replication, pathogenicity, and host immune responses

International audienceAbstractAs a key cellular transcription factor that plays a central role in cellular responses to a broad range of stress factors, p53 has generally been considered as a host cell restriction factor for various viral infections. However, the defined roles of p53 in pseudorabies virus (PRV) replication, pathogenesis, and host responses remain unclear. In the present study, we initially constructed a p53 overexpressing a porcine kidney epithelial cell line (PK-15) to detect the effect of p53 on PRV replication in vitro. The results show that viral glycoprotein B (gB) gene copies and the titers of virus were significantly higher in p53 overexpressing PK-15 cells than in PK-15 and p53 inhibitor treated p53 overexpressing PK-15 cells. A similar result was also found in the p53 inhibitor PFT-α-treated PK-15 cells. We then examined the effects of p53 on PRV infection in vivo by using p53-knockout (p53−/−) mice. The results show that p53 knockout not only led to significantly reduced rates of mortality but also to reduced viral replication and development of viral encephalitis in the brains of mice following intracranial inoculation. Furthermore, we examined the effect of p53 knockout on the expression of the reported host cell regulators of PRV replication in the brains of mice by using RNA sequencing. The results show that p53 knockout downregulated the interferon (IFN) regulator genes, chemokine genes, and antiviral genes after PRV infection. This finding suggests that p53 positively regulates viral replication and pathogenesis both in vitro and in vivo. These findings offer novel targets of intrinsic host cell immunity for PRV infection

Evaluation of pharmacist-led telemedicine medication management for hypertension established patients during COVID-19 pandemic: A pilot study

AimTo evaluate the impact of a telemedicine medication management service in patients with hypertension.MethodsParticipants were allocated to either a telemedicine service (N = 173) or usual care (UC) (N = 179). The primary outcome was blood pressure (BP) reduction from baseline to the 6-month follow-up visit, the proportion of the target BP achievement, overall adherence to prescribed medication as well as a composite of non-fatal stroke, non-fatal myocardial infarction and cardiovascular death.ResultsAt 6 months, BP was controlled in 89.6% (n = 155) of intervention patients and 78.8% (n = 141) of UC patients (OR = 1.14, 95% CI = 1.04–1.25, P = 0.006), giving a mean difference of −6.0 (−13.0 to −2.5 mmHg) and −2.0 mmHg (−4.0 to −0.1 mmHg) in SBP and DBP, respectively. 17.9% (n = 31) of the patients in the intervention group were non-adherent with medications, compared with 29.1% (n = 52) in the UC group (P = 0.014). The composite clinical endpoints were reached by 2.9% in the intervention group and 4.5% in the control group with no significant differences (OR = 1.566, 95% CI = 0.528–4.646).ConclusionTelemedicine medication management for hypertension management had led to better BP control and medication adherence improvement than UC during COVID-19 epidemic, resulting in a reduction of overall adverse cardiovascular events occurrence

NCNet: Deep Learning Network Models for Predicting Function of Non-coding DNA

The human genome consists of 98.5% non-coding DNA sequences, and most of them have no known function. However, a majority of disease-associated variants lie in these regions. Therefore, it is critical to predict the function of non-coding DNA. Hence, we propose the NCNet, which integrates deep residual learning and sequence-to-sequence learning networks, to predict the transcription factor (TF) binding sites, which can then be used to predict non-coding functions. In NCNet, deep residual learning networks are used to enhance the identification rate of regulatory patterns of motifs, so that the sequence-to-sequence learning network may make the most out of the sequential dependency between the patterns. With the identity shortcut technique and deep architectures of the networks, NCNet achieves significant improvement compared to the original hybrid model in identifying regulatory markers

Mitigation of severe urban haze pollution by a precision air pollution control approach

Severe and persistent haze pollution involving fine particulate matter (PM_(2.5)) concentrations reaching unprecedentedly high levels across many cities in China poses a serious threat to human health. Although mandatory temporary cessation of most urban and surrounding emission sources is an effective, but costly, short-term measure to abate air pollution, development of long-term crisis response measures remains a challenge, especially for curbing severe urban haze events on a regular basis. Here we introduce and evaluate a novel precision air pollution control approach (PAPCA) to mitigate severe urban haze events. The approach involves combining predictions of high PM_(2.5) concentrations, with a hybrid trajectory-receptor model and a comprehensive 3-D atmospheric model, to pinpoint the origins of emissions leading to such events and to optimize emission controls. Results of the PAPCA application to five severe haze episodes in major urban areas in China suggest that this strategy has the potential to significantly mitigate severe urban haze by decreasing PM_(2.5) peak concentrations by more than 60% from above 300 μg m^(−3) to below 100 μg m^(−3), while requiring ~30% to 70% less emission controls as compared to complete emission reductions. The PAPCA strategy has the potential to tackle effectively severe urban haze pollution events with economic efficiency

Evaluation of the Effects of Cold Plasma on Cell Membrane Lipids and Oxidative Injury of Salmonella typhimurium

Salmonella typhimurium (S. typhimurium) is a major causative agent of foodborne illness worldwide. Cold plasma (CP) was used to inactivate S. typhimurium and to investigate the effect of CP on cell membrane lipids and oxidative injury of cells. Results indicated that the inactivation effect of CP on S. typhimurium was positively correlated with the treatment time and voltage. S. typhimurium was undetectable (total number of surviving colonies <2 log CFU/mL) after 5 min treatment with the voltage of 50 V. CP treatment caused damage to the cell membrane of S. typhimurium and the leakage of cell contents, and the relative content of unsaturated fatty acids in cell membrane decreased. Cell membrane lipids were oxidized; the malondialdehyde content increased from 0.219 nmol/mL to 0.658 nmol/mL; the catalase activity of S. typhimurium solution increased from 751 U/mL to 2542 U/mL; and the total superoxide dismutase activity increased from 3.076 U/mL to 4.54 U/mL, which confirmed the oxidative damage in S. typhimurium cell membrane caused by CP treatment. It was demonstrated that the potential application of plasma-mediated reactive oxygen species is suitable for destroying the structures of the cell membrane and ensuring the microbial safety of fresh food samples