Bone Marrow Mesenchymal Stem Cells (BMSCs)-Exosome Inhibits Epithelial Ovarian Cancer (EOC) Cell Proliferative Ability Through Regulating Mitogen-Activated Protein Kinase (MKP)-1 and Mitogen-Activated Protein Kinases (MAPK)/Extracellular-Signal-Regulated Kinase (ERK) Signal Pathway

The BMSCs-exosome plays a role in regulating tumor micro-environment so as to affect tumor cell biological behaviors. However, whether it affects the biological characteristics of epithelial ovarian cancer (EOC) cells remains unclear. Our study aimed to discuss whether BMSCs-exosome affects EOC cell proliferative ability. BMSCs cells were cultivated to isolate exosome which was used to treat EOC cells at different concentrations (25, 50, and 100 μmol/L) followed by measuring cell proliferation by CCK-8, cell invasion and migration by Transwell, MKP-1and MAPK/ERK protein level by Western Blot. BMSCs-exosome showed positive expression of CD9, CD63 and CD81 and negative CD116 and CD19. It could significantly inhibit EOC cell proliferation, invasion and migration in a dose-dependent manner along with reduced expression of MAPK/ERK. In conclusion, BMSCs-exosome inhibits EOC cell biological behaviors possibly through regulation of MKP-1 and MAPK/ERK signal pathway, indicating that it might be used as a novel approach for treating EOC.

The Mechanism of Human Umbilical Mesenchymal Stem Cells (HUMSC) on Biological Behavior of Human Papillomavirus (HPV) Cells Through Restraining the Programmed Cell Death Protein 1/Programmed Cell Death Ligand 1 (PD-1/PD-L1) Signal Pathway

Biological behavior of HPV cell was observed by HUMSC through restraining PD-1/PD-L1 signal pathway. And HUMSC was adopted as target cell for the treatment on HPV. The rat HPV model was established and divided into three groups including blank group, control group and test group according to different reagents being injected into rats. Use HE staining method to observe the cancerous transformation of tumor tissue sections. The gene presentation of PD-1/PD-L1 and lymphocyte was detected with Western blot. The invasion and migration condition of cancer cells was observed from experiment in vitro. The quantity of cancer cells in test group was the least. And invasion and migration ability in test group was the weakest. The control group was the second. The number of tumor cells in the blank group was the largest. Strongest ability to invade and migrate. The presentation of PD-L1 was restrained partly by HUMSC. The increasing of immune-associated cells could be prompted by HUMSC. The quantity of CD3+, CD4+ and CD8+ in PB was the most in test group. The expression of blank groups is the lowest than others restrained by HUMSC. And quantity of abundant immune cells including CD3+, CD4+ and CD8+ could be activated partly through activating immune action of body. And monitoring function of immune system on HPV cells could be increased effectively. The invasion and migration ability in vitro of HPV could be reduced partly.

Hepatocellular Carcinoma Differentiation: Research Progress in Mechanism and Treatment

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver. Although progress has been made in diagnosis and treatment, morbidity and mortality continue to rise. Chronic liver disease and liver cirrhosis are still the most important risk factors for liver cancer. Although there are many treatments, it can only be cured by orthotopic liver transplantation (OLT) or surgical resection. And the worse the degree of differentiation, the worse the prognosis of patients with liver cancer. Then it can be considered that restoring a better state of differentiation may improve the prognosis. The differentiation treatment of liver cancer is to reverse the dedifferentiation process of hepatocytes to liver cancer cells by means of drugs, improve the differentiation state of the tumor, and restore the normal liver characteristics, so as to improve the prognosis. Understanding the mechanism of dedifferentiation of liver cancer can provide ideas for drug design. Liver enrichment of transcription factors, imbalance of signal pathway and changes of tumor microenvironment can promote the occurrence and development of liver cancer, and restoring its normal level can inhibit the malignant behavior of tumor. At present, some drugs have been proved to be effective, but more clinical data are needed to support the effectiveness and reliability of drugs. The differentiation treatment of liver cancer is expected to become an important part of the treatment of liver cancer in the future.

TRIP13 Activates the PI3K/AKT Signal Pathway to Promote Melanoma Progression by Interacting With FLNA

Background: Skin melanoma is a malignant tumor originated from skin melanocytes. It is highly malignant and easy to relapse and metastasis. Finding new diagnostic and therapeutic targets has become a hot issue. Accumulating evidence now indicates that thyroid hormone receptor interactor 13 (TRIP13) plays important roles in tumor development. However, its role in melanoma remains unclear.Methods: Bioinformatic analyses were employed to excavate crucial genes in melanoma using several public databases. The expression of TRIP13 was detected by immunohistochemistry. MV3 cell and A2058 cell were steadily transfected with TRIP13 knock-down or overexpression lentiviruses, then the function and potential mechanism of TRIP13 were studied in vitro and in vivo. Co-immunoprecipitation (Co-IP) and mass spectrum were employed to screen out the interacting molecule of TRIP13.Results: Our results showed that TRIP13 was generally upregulated in melanoma tissues and was related to the poor prognosis of melanoma patients. The overexpression of TRIP13 promotes the invasion, migration and EMT transformation of melanoma cells in vitro, and promotes lung metastasis in vivo. Mechanismly, TRIP13 interacts with FLNA, and activates the PI3K/AKT pathway, and then induces melanoma migration, invasion and EMT transformation.Conclusion: Elevated TRIP13 drives tumor progression via the FLNA/PI3K/AKT axis, and TRIP13 is a innovative prognostic molecule and potential target of targeted therapy in melanoma.

Identification of Molecular Biomarkers Associated With Stroke Progression Using WGCNA and SVM-RFE

Background: Stroke is the second most common cause of death worldwide and the leading cause of long-term severe disability with neurological impairment worsening within hours after stroke onset and being especially involved with motor function. So far, there are no established and reliable biomarkers to prognose stroke. Early detection of biomarkers that can prognose stroke is of great importance for clinical intervention and prevention of clinical deterioration of stroke.Methods: TGSE119121 dataset was retrieved from the Gene Expression Integrated Database (Gene Expression Omnibus, GEO) and weighted gene co-expression network analysis (WGCNA) was conducted to identify the key modules that could regulate disease progression. Moreover, functional enrichment analysis was conducted to study the biological functions of the key module genes. The GSE16561 dataset was further analyzed by the Support Vector Machines coupled with Recursive Feature Elimination (SVM-RFE )algorithm to identify the top genes regulating disease progression. The hub genes revealed by WGCNA were associated with disease progression using the receiver operating characteristic curve (ROC) analysis. Subsequently, functional enrichment of the hub genes was performed by deploying gene set variation analysis (GSVA). The changes at gene level were transformed into the changes at pathway level to identify the biological function of each sample. Finally, the expression level of the hub gene in the rat infarction model of MCAO was measured using RT-qPCR for validation. Results: WGCNA analysis revealed four hub genes: DEGS1, HSDL2, ST8SIA4 and STK3. The result of GSVA showed that the hub genes were involved in stroke progression by regulating the p53 signal pathway, the PI3K signal pathway, and the inflammatory response pathway. The results of RT-qPCR indicated that the expression of the four HUB genes was increased significantly in the rat model of MCAO.Conclusion: Several genes, such as DEGS, HSDL2, ST8SIA4 and STK3, were identified and associated with the progression of the disease. Moreover, it was hypothesized that these genes may be involved in the progression stroke by regulating the P53 signal, the PI3K signal, and the inflammatory response pathway, respectively. These genes have potential prognostic value and may serve as biomarkers for predicting stroke progression. The early identification of the patients at risk of progression is essential to prevent clinical deterioration and provide a reference for future research.

Regeneration of duckweed (Lemna turonifera) involves genetic molecular regulation and cyclohexane release

Plant regeneration is important for vegetative propagation, detoxification and the obtain of transgenic plant. We found that duckweed regeneration could be enhanced by regenerating callus. However, very little is known about the molecular mechanism and the release of volatile organic compounds (VOCs). To gain a global view of genes differently expression profiles in callus and regenerating callus, genetic transcript regulation has been studied. Auxin related genes have been significantly down-regulated in regenerating callus. Cytokinin signal pathway genes have been up-regulated in regenerating callus. This result suggests the modify of auxin and cytokinin balance determines the regenerating callus. Volatile organic compounds release has been analysised by gas chromatography/ mass spectrum during the stage of plant regeneration, and 11 kinds of unique volatile organic compounds in the regenerating callus were increased. Cyclohexane treatment enhanced duckweed regeneration by initiating root. Moreover, Auxin signal pathway genes were down-regulated in callus treated by cyclohexane. All together, these results indicated that cyclohexane released by regenerating callus promoted duckweed regeneration. Our results provide novel mechanistic insights into how regenerating callus promotes regeneration.