MiR-181c-5p ameliorates learning and memory in sleep-deprived mice via HMGB1/TLR4/NF-κB pathway.

Sleep deprivation (SD) can lead to cognitive impairment caused by neuroinflammation. MiR-181c-5p/HMGB1 axis plays a part in anti-inflammation effects. However, the mechanism that miR-181c-5p facilitates learning and memory in SD mice remains unclear. So we investigated the role of miR-181c-5p in learning and memory impairment induced by SD. We overexpressed miR-181c-5p in the mice hippocampus by injecting lentivirus vector-miR-181c-5p (LV-miR-181c-5p) particles. Mice were divided into four groups: control (Ctrl), SD, SD + miR-181c-5p and SD + vector. We found that mice in the third group showed ameliorated learning and memory compared with the fourth group. The content of ionized calcium binding adaptor molecule 1 (IBA-1) in the third group was decreased compared with the fourth group. Moreover, the expression levels of HMGB1, TLR4 and p-NF-κB in the hippocampus of overexpressed miR-181c-5p mice were reduced. In total, miR-181c-5p ameliorated learning and memory in SD mice via the HMGB1/TLR4/NF-κB pathway.

Bioinformatic Analysis of PTTG Family and Prognosis and Immune Cell Infiltration in Gastric Cancer.

Gastric cancer is the sixth highest incidence rate in the world. Although treatment has made progress, the prospect of gastric cancer patients is bleak. Difficulties and future prospects of immunotherapy in cancer treatment. Adaptive cell therapy, cancer vaccines, gene therapy, and monoclonal antibody therapy have all been used in gastric cancer with some initial success. PTTGs (pituitary tumor-transforming genes) have been proven to be closely related to the prognosis of many malignant tumors. However, the prognosis and immune cell infiltration of gastric adenocarcinoma (STAD) remain unclear. We retrieved multiple databases to understand the possible activity of PTTGs and their expression in gastric cancer, as well as their relationship with clinical data, overall survival rate, first progression, and survival rate after progression. PTTGs are overexpressed in STAD tumor tissues. Many clinical variables are closely related to PTTGs. In addition, PTTG was associated with overall survival independent of disease. In addition, the expression of PTTG1/2 was positively correlated with the molecular status of the immune checkpoint and negatively correlated with the infiltration of various immune cells. Data research shows that PTTG and STAD are closely related. This paved the way for future research, revealed the complex pathophysiology of gastric cancer, and introduced an effective new treatment.

Melatonin upregulates BMAL1 to attenuate chronic sleep deprivation-related cognitive impairment by alleviating oxidative stress.

PURPOSE: To investigate the mechanism underlying the regulatory effect of melatonin on chronic sleep deprivation-related cognitive impairment. METHODS: Chronic sleep deprivation (CSD) model was established using the MMPM method. After the model was established, melatonin receptor agonist and inhibitor were given, respectively. Water maze was conducted to record the escape latency and the duration of crossing the platform of space exploration. The concentration of TNF-α, IL-6, MDA, and SOD was measured by ELISA. Immunofluorescence was used to determine the expression level of CD86 and CD206, while the mRNA expression of Bax, Bcl-2, P65, IκB, and BMAL1 was detected by qPCR. Western blotting assay was utilized to determine the protein expression of Bax, Bcl-2, P65, p-P65, IκB, p-I κB, and BMAL1. RESULTS: Compared with the control, the escape latency was greatly increased on the second and third day, accompanied by the increased expression of TNF-α, IL-6, MDA, and SOD in serum. Furthermore, dramatically upregulated Bax, Bcl-2, P65, IκB, and CD86 were observed in the model group, accompanied by the declined expression level of BMAL1 and CD206. Compared with the model group, the escape latency was declined, the concentration of TNF-α, IL-6, MDA, and SOD was decreased, the expression level of Bax, Bcl-2, P65, IκB, and CD86 was declined, and the level of BMAL1 and CD206 was promoted by the treatment of the melatonin agonist, while the opposite results were observed under the treatment of the melatonin inhibitor. CONCLUSION: Melatonin upregulates BMAL1 to attenuate chronic sleep deprivation-related cognitive impairment by alleviating oxidative stress.

Bioinformatics analysis: relationship between adrenocortical carcinoma and KIFs.

Adrenal cortical cancer has a relatively low incidence, but a dismal 5-year survival rate. Surgical intervention is the gold standard of care today. In spite of this progress, patients continue to have a dismal outlook. The results of this study demonstrate that kinin superfamily (KIF) has strong ties to many different types of cancers. However, their prognostic and immune cell infiltration of adrenocortical carcinoma (ACC) remain unclear. Multiple databases were searched for information on the transcription level of KIFs, its correlation with clinical data of ACC patients, patients' overall survival (OS), first progression survival (FPS), and progression free interval (PFI). Its role and association with immune cells were also investigated. We observed an increase in the expression of KIF4A, KIF11, KIF20A, and KIF22. There was a strong correlation between them and the advancedness of ACC tumors. Parallel to this, KIFs are connected to the concepts of operating systems, distributed file systems, and partitioned file systems. Similarly, we found five key genes, PRC1, PLK1, KIF23, KIFC1, and KIF5A, through data analysis, all of which participate in multiple cellular pathways. Both KIF4A and KIF11 expression levels were marginally positively correlated with immune infiltration. Because KIF4A, KIF11, KIF20A, and KIF22 are involved in multiple ACC processes and can influence the onset and progression of ACC, they provide a mechanistically grounded framework for diagnosing and managing the disease.

The targets of aspirin in bladder cancer: bioinformatics analysis.

BACKGROUND: The anti-carcinogenic properties of aspirin have been observed in some solid tumors. However, the molecular mechanism of therapeutic effects of aspirin on bladder cancer is still indistinct. We introduced a bioinformatics analysis approach, to explore the targets of aspirin in bladder cancer (BC). METHODS: To find out the potential targets of aspirin in BC, we analyzed direct protein targets (DPTs) of aspirin in Drug Bank 5.0. The protein-protein interaction (PPI) network and signaling pathway of aspirin DPTs were then analyzed subsequently. A detailed analysis of the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway has shown that aspirin is linked to BC. We identified overexpressed genes in BC comparing with normal samples by Oncomine and genes that interlinked with aspirin target genes in BC by STRING. RESULTS: Firstly, we explored 16 direct protein targets (DPT) of aspirin. We analyzed the protein-protein interaction (PPI) network and signaling pathways of aspirin DPT. We found that aspirin is closely associated with a variety of cancers, including BC. Then, we classified mutations in 3 aspirin DPTs (CCND1, MYC and TP53) in BC using the cBio Portal database. In addition, we extracted the top 50 overexpressed genes in bladder cancer by Oncomine and predicted the genes associated with the 3 aspirin DPTs (CCND1, MYC and TP53) in BC by STRING. Finally, 5 exact genes were identified as potential therapeutic targets of aspirin in bladder cancer. CONCLUSION: The analysis of relevant databases will improve our mechanistic understanding of the role of aspirin in bladder cancer. This will guide the direction of our next drug-disease interaction studies.