Activation of the Nrf2/HO-1 axis by glutaredoxin 2 overexpression antagonizes vascular endothelial cell oxidative injury and inflammation under LPS exposure.

Atherosclerosis constitutes a proverbial pathogenic mechanism for cardio-cerebrovascular disease that accounts for the most common cause of disability and morbidity for human health worldwide. Endothelial dysfunction and inflammation are the key contributors to the progression of atherosclerosis. Glutaredoxin 2 (GLRX2) is abundantly existed in various tissues and possesses a range of pleiotropic efficacy including anti-oxidative and anti-inflammatory responses. However, its role in atherosclerosis is still undefined. Here, down-regulation of GLRX2 was validated in lipopolysaccha (LPS)-induced vascular endothelial cells (HUVECs). Moreover, elevation of GLRX2 reversed the inhibition of cell viability in LPS-treated HUVECs and decreased LPS-induced increases in cell apoptosis and caspase-3 activity. Additionally, enhancement of GLRX2 expression antagonized oxidative stress in HUVECs under LPS exposure by inhibiting ROS, lactate dehydrogenase and malondialdehyde production and increased activity of anti-oxidative stress superoxide dismutase. Notably, GLRX2 abrogated LPS-evoked transcripts and releases of pro-inflammatory cytokine (TNF-α, IL-6, and IL-1ß), chemokine MCP-1 and adhesion molecule ICAM-1 expression. Furthermore, the activation of Nrf2/HO-1 signaling was demonstrated in LPS-stimulated HUVECs. Importantly, blockage of the Nrf2 pathway counteracted the protective roles of GLRX2 in LPS-triggered endothelial cell injury, oxidative stress and inflammatory response. Thus, these data reveal that GLRX2 may alleviate the progression of atherosclerosis by regulating vascular endothelial dysfunction and inflammation via the activation of the Nrf2 signaling, supporting a promising therapeutic approach for atherosclerosis and its complications. Supplementary Information: The online version contains supplementary material available at 10.1007/s10616-023-00606-x.

High-expressed PTPN1 promotes tumor proliferation signature in human hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a highly prevalent malignant tumor that is associated with substantial morbidity and mortality rates. Despite the progress made in diagnostic technology, the survival rate of HCC patients remains unsatisfactory due to the complex nature and extensive metastasis of the disease. Consequently, the discovery of new molecular targets is of great practical significance for the diagnosis and treatment of HCC. Protein tyrosine phosphatases (PTPs) play a crucial role in cell signal transduction by catalyzing the dephosphorylation of tyrosine residues in proteins. The present study has revealed that the upregulation of protein tyrosine phosphatase non-receptor type 1 (PTPN1) is a characteristic feature of HCC and is associated with a poor prognosis. Additionally, our investigation into the functional roles of PTPN1-regulated genes in HCC has demonstrated that alterations in PTPN1 expression disrupt normal cell cycle progression metabolism. Additionally, the capacity for proliferation and migration of HCC cells was notably diminished subsequent to PTPN1 silencing, resulting in the prevention of cell entry into the S phase from the G1 phase. Our investigation indicates that PTPN1 may facilitate the onset and progression of HCC by disrupting the cell cycle, thereby presenting a promising molecular target for the diagnosis and treatment of liver cancer.

Effects of Residual Composition and Distribution on the Structural Characteristics of the Protein.

The effect of ratio and consecutive number of hydrophobic residues in the repeating unit of protein chains was investigated by MD simulation. The modified off-lattice HNP model was applied in this study. The protein chains constituted by different HNP ratios or different numbers of consecutively hydrophobic residues with the same chain length were simulated under a broad temperature range. We concluded that the proteins with higher ratio or larger number of sequentially hydrophobic residues present more orientated and compact structure under a certain low temperature. It is attributed to the lower non-bonded potential energy between H-H residual pairs, especially more hydrophobic residues in a procession among the protein chain. Considering the microscopic structure of the protein, more residue contacts are achieved with the proteins with higher ratios and sequential H residues under the low temperature. Meanwhile, with the ratio and consecutive number of H residues increasing, the distribution of stem length showed a transition from exponential decline to unimodal and even multiple peaks, indicating the specific ordered structure formed. These results provide an insight into 3D structural properties of proteins from their residue sequences, which has a primary structure at molecular level and, ultimately, a practical possibility of applying in biotechnological applications.

Accuracy of C-Reactive Protein Test for Neonatal Septicemia: A Diagnostic Meta-Analysis.

BACKGROUND The aim of this study was to evaluate the diagnostic value of C-reactive protein (CRP) test in detecting neonatal septicemia. MATERIAL AND METHODS We searched the Cochrane Library, PubMed, Springer, MBASE, Elsevier Science Direct, and Medline databases up to March 2017. To collect relevant data on CRP testing in patients with neonatal septicemia, we performed a meta-analysis of positive likelihood ratio (LR), sensitivity, negative LR, specificity and diagnostic odds ratio (dOR) of CRP testing, using Stata 12.0 and Meta-DiSc 1.4 data analysis software. RESULTS Ten studies including 1819 participants were considered in this study. We found that positive LR, sensitivity, negative LR, specificity, and dOR of the CRP test for neonatal septicemia were 5.63 (95% CI=2.86 to 11.09), 0.70 (95% CI=0.66 to 0.75), 0.36 (95% CI=0.21 to 0.60), 0.89 (95% CI=0.87 to 0.91), and 17.99 (95% CI=6.50 to 49.83), respectively. The AUC and Q* index of this meta-analysis were 0.90 and 0.83, respectively. CONCLUSIONS The area under the curve (AUC), negative LR, positive LR, Q* index, specificity, and dOR of the CRP test suggest that it is appropriate for detecting neonatal septicemia.