Dynamic changes of inflammatory response and oxidative stress induced by methicillin-resistant Staphylococcus aureus in mice.

This study is to analyze the dynamic changes of inflammation and oxidative stress in mice infected with MRSA and to provide experimental basis for clinically formulating reasonable treatment plans. We established a model of MRSA infection in mice, detected the fluctuations in the concentration of proinflammatory cytokines and oxidative stress factors with time, and combined with the results of microscopic examination of tissue sections to explain the infection in vivo caused by MRSA. The results showed that on the 1st, 3rd, and 7th day of MRSA infection, the number of leukocytes and eosinophils decreased at first and then increased, monocytes increased continuously, and neutrophils and basophils decreased. At the same time, the levels of proinflammatory cytokines IL-1ß, IL-6, and TNF-α increased. The concentration of glutathione peroxide decreased, and the oxidative metabolites increased. Tissue sections also showed that inflammation and oxidative stress occurred in mice. It is obvious that MRSA infection can lead to significant inflammation and oxidative stress. Therefore, while treating MRSA infection, attention should be paid to the levels of inflammation and oxidative stress in different periods to achieve better treatment effects.

Inflammatory and pathological changes in Escherichia coli infected mice.

Purpose: Understanding the inflammation and histopathological changes in vivo caused by Escherichia coli infection is of great significance for scientific research and clinical diagnosis. Methods: Mice were randomly divided into 6 groups (N = 10) after adaptive feeding, and it challenged by intraperitoneal injection with different concentrations of E. coli ATCC25922. The survival situation within 7 days was recorded, and the half-lethal dose (LD50) was calculated by Karber's method. After the end, the blood, heart, liver, spleen, lung, and kidney of the mice were collected. We detected the concentration of inflammatory cytokines (IL-6, IL-ß, and TNF-α) and inducible nitric oxide synthase (iNOS) in serum by ELSIA. Organs were observed by histopathological staining and electron microscope observation. Results: The LD50 of mice infected with E. coli was 1.371∗106 CFU/kg. The concentrations of IL-6, IL-ß, and TNF-α increased with time after infection in mice, reaching the highest concentration on the 7th day. iNOS was significantly increased on the 1st day of infection, and then decreased over time (P < 0.01). Within a week after infection, the colony counts of the heart, liver, spleen, lung and kidney showed a first decrease, and then reached a surge on the 7th day. Pathological results showed that a small amount of mitochondrial swelling and autophagy were seen in the spleen, lung and kidney tissues of the infected group; and a small amount of secondary lysosomes and autophagy were also seen; but no pathological changes were found in the liver and heart. Conclusion: Escherichia coli can cause inflammation and oxidative stress in mice, causing different degrees of damage to the spleen, lung, and kidney tissues, which provides theoretical support for inflammatory and pathological changes caused by Escherichia coli infection in vivo.

TP53-Activated lncRNA GHRLOS Regulates Cell Proliferation, Invasion, and Apoptosis of Non-Small Cell Lung Cancer by Modulating the miR-346/APC Axis.

Non-small cell lung cancer (NSCLC) is the main type of lung cancer with high mortality worldwide. To improve NSCLC therapy, the exploration of molecular mechanisms involved in NSCLC progression and identification of their potential therapy targeting is important. Long noncoding RNAs (lncRNAs) have shown important roles in regulating various tumors progression, including NSCLC. We found lncRNA GHRLOS was decreased in NSCLC cell lines and tissues which correlated with poor prognosis of NSCLC patients. However, the role and underlying mechanisms of lncRNA GHRLOS in NSCLC progression remains elusive. The expression of lncRNA GHRLOS was examined in NSCLC cell lines and biopsy specimens of patients with NSCLC by quantitative real time polymerase chain reaction (qRT-PCR). The effects of GHRLOS on proliferation, invasion and apoptosis of NSCLC cells were determined by both in vitro and in vivo experiments. The interaction between GHRLOS and TP53 was determined by dual-luciferase reporter assay and chromatin immunoprecipitation (ChIP) combined with qRT-PCR analysis. RNA immunoprecipitation (RIP) was conducted to validate the binding between GHRLOS and microRNA-346 (miR-346). Dual-luciferase reporter assays were also carried out to reveal the interaction between miR-346 and the 3' untranslated region (3'UTR) of adenomatous polyposis coli (APC) mRNA.Our data demonstrated that overexpression of lncRNA GHRLOS suppressed cancer cell proliferation and invasion as well as promoted cell apoptosis by regulating the expression of CDK2, PCNA, E-cadherin, N-cadherin, Bax, and Bcl-2 in NSCLC cells. Moreover, lncRNA GHRLOS was upregulated by the binding of TP53 to the GHRLOS promoter. The binding target of lncRNA GHRLOS was identified to be miR-346. Impressively, overexpression of miR-346 promoted cell proliferation and invasion, as well as inhibited cell apoptosis, however, these effects can be blocked by overexpression of lncRNA GHRLOS both in vitro and in vivo. In summary, this study reveals lncRNA GHRLOS, upregulated by TP53, acts as a molecule sponge of miR-346 to cooperatively modulates expression of APC, a miR-346 target, and potentially inhibits NSCLC progression via TP53/lncRNA GHRLOS/miR-346/APC axis, which represents a novel pathway that could be useful in targeted therapy against NSCLC.