mRNA expression level of CDH2, LEP, POSTN, TIMP1 and VEGFC modulates 5-fluorouracil resistance in colon cancer cells

xlomafota13 shared this article with you from Inoreader mRNA expression level of <em>CDH2</em>, <em>LEP</em>, <em>POSTN</em>, <em>TIMP1</em> and <em>VEGFC</em> modulates 5-fluorouracil resistance in colon cancer cells Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):1023. doi: 10.3892/etm.2021.10455. Epub 2021 Jul 15. ABSTRACT Drug resistance severely affects the clinical efficacy of therapeutic agents in patients with colon cancer. The aim of the present study was to identify genes involved in drug resistance in colon cancer using bioinformatics analysis and to identify the underlying mechanisms in vitro. Genes associated with cancer recurrence and chemotherapy resistance were identified using data mining. Immunohistochemistry was performed to analyze the protein expression level of genes of interest in human colon cancer tissues. Reverse transcription-quantitative PCR analysis was performed to analyze the gene expression level in patient samples and in colon cancer cell lines (HCT116 and LoVo). Cell viability was evaluated using the Cell Counting Kit-8 assay in the colon cancer cell lines. Apoptosis was measured using PI staining. The results from the present study revealed 602 genes using both 'cancer recurrence' and 'chemoresistance' terms on the GenCLiP3 website. Gene functional annotation was performed using the Database for Annotation, Visualization and Integrated Discovery then, the protein-protein interaction networks of the 602 genes were analyzed using STRING analysis. Further, in the GEPIA database, 14 genes (ATM, CDH2, CDKN2A, EPO, LEP, TGFB1, TIMP1, PGR, VEGFC, POSTN, BCL6, CYP19A1, NOTCH3 and XPA) were found to be upregulated in colon cancer tissue and were associated with poor prognosis in patients with colon cancer. Further analysis of 33 paired human colon cancer tissues revealed that 8 genes (ATM, CDH2, CDKN2A, LEP, PGR, TIMP1, POSTN and VEGFC) were significantly upregulated, which was consistent with the results obtained from the earlier analysis and 5 genes (CDH2, LEP, POSTN, TIMP1 and VEGFC) were associated with patient prognosis. Silencing of these 5 genes using small interfering RNAs significantly enhanced the sensitivity of colon cancer cells to the chemotherapeutic agent, 5-fluorouracil (5-FU). Taken together, the results suggested that CDH2, LEP, POSTN, TIMP1 and VEGFC might play a role in chemotherapeutic resistance in colon cancer and represent potential targets for overcoming 5-FU resistance in colon cancer. PMID:34373709 | PMC:PMC8343572 | DOI:10.3892/etm.2021.10455 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

COVID-19 pandemic and reasons to prioritize the needs of the health care system to ensure its sustainability: A scoping review from January to October 2020 (Review)

xlomafota13 shared this article with you from Inoreader COVID-19 pandemic and reasons to prioritize the needs of the health care system to ensure its sustainability: A scoping review from January to October 2020 (Review) Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):1039. doi: 10.3892/etm.2021.10471. Epub 2021 Jul 21. ABSTRACT The worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led the World Health Organization to characterize the pandemic as a public health emergency of international concern. National health care systems in countries during the initial surge of the pandemic were unable to handle the sanitarian crisis that had emerged. Thus, the prevention and control of future global health emergencies must be a priority. The present scoping review aimed to retrieve articles that summarize the current experience on issues related to historical knowledge, and epidemiology, clinical features and overall burden of SARS-CoV-2 on health care services. In summary, a comprehensive overview of the information that has been learnt during this period is presented in the current review. Furthermore, taking into account the global experience, the need for planning cohesive and functional health services before similar pandemic events occur in the future is highlighted. The next public health issue should be prevented rather than treated. In spite of the vaccination benefits, a number of sporadic cases of SARS-CoV-2infections will persist. Information collected remains relevant for appraising how similar threats can be faced in the future. Overall, collaborative health care plans need to be rethought to increase preparedness. PMID:34373725 | PMC:PMC8343896 | DOI:10.3892/etm.2021.10471 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Musculoskeletal adverse reactions after immunotherapy for cancer: A case series

xlomafota13 shared this article with you from Inoreader Musculoskeletal adverse reactions after immunotherapy for cancer: A case series Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):1027. doi: 10.3892/etm.2021.10459. Epub 2021 Jul 16. ABSTRACT Immunotherapy has revolutionized cancer treatment. Immune checkpoint inhibitors (ICIs) including antibodies targeting cytotoxic T lymphocyte associated antigen-4 and programmed cell death 1 have been shown to be effective in the treatment of certain types of cancer. The benefit of these therapies is to prolong life expectancy in the case of metastatic malignancies. Rheumatic adverse events are not very common. In the present study, 9 patients were monitored between November 2018 and January 2020. The oncologist, who identified the occurrence of rheumatic toxicities after the treatment with ICIs, evaluated the patients. Only oncological patients with rheumatic manifestations after the start of immunotherapy were included. Toxicity grading was performed by both the oncologist and the rheumatologist, on a scale from 1 to 5 (1, mild; 2, moderate; 3, severe; 4, life-threatening; 5, death related to toxicity). The results showed that rheumatoid factor, which was sampled in each patient, was negative in all cases. Patients were treated with nonsteroidal anti-inflammatory drugs or prednisone depending on the severity of the adverse events. The results varied with the severity of the adverse events. In conclusion, as the number of patients treated with ICIs increases, so will the number of patients presenting with immune-related adverse events (irAEs). The collaboration between oncologists and rheumatologists should be intimate to provide optimal treatment to patients. Musculoskeletal manifestations secondary to ICIs are slightly different from other rheumatologically conditions making diagnosis, treatment and monitoring difficult. Thus, irAEs are new and challenging for oncologists, thus understanding of the pathogenesis and clinical characteristics must be improved for better treatment guidelines. PMID:34373713 | PMC:PMC8343871 | DOI:10.3892/etm.2021.10459 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Autonomic regulation of imbalance-induced myocardial fibrosis and its mechanism in rats with cirrhosis

xlomafota13 shared this article with you from Inoreader Autonomic regulation of imbalance-induced myocardial fibrosis and its mechanism in rats with cirrhosis Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):1040. doi: 10.3892/etm.2021.10472. Epub 2021 Jul 21. ABSTRACT The aim of the present study was to investigate the changes in cardiac function and myocardial damage in rats with cirrhosis. In addition, a secondary aim was to explore any potential changes in the expression levels of β1-adrenergic (β1) and muscarinic acetylcholine (M2) receptors . A cirrhotic cardiomyopathy (CCM) rat model was established by CCL4-oil solution for subcutaneous injection into the neck. Pathological changes in the liver and myocardial tissues were detecting by H&E staining and Masson trichrome staining. Furthermore, changes in the levels of myocardial enzymes lactate dehydrogenase (LDH), creatine kinase isoenzyme (CK-MB) and troponin in serum were measured by ELISA. The myocardial samples were homogenized and centrifuged. Subsequently, the supernatant was collected for detecting the expression of interleukins in myocardial tissue. Changes in the levels of inflammatory factors, IL-1, IL-2 and IL-6 both in the serum and myocardial tissue were determined by ELISA. Changes in echocardiographic measurements were evaluated using high-frequency ultrasound and the expression levels of β1 and M2 receptors in myocardial tissues were determined by western blotting. The normal lobular structure in liver tissues was found to be disappeared 8 weeks after modeling, which was replaced by pseudolobules in the rats in the CCM group. In addition, the myocardial cells were observed to be swollen and disorderly arranged. Compared with those in the control group, the left ventricular end-systolic and end-diastolic dimensions, interventricular septal dimension and LAD in rats in the CCM8 group were found to be significantly increased. The levels of myocardial enzymes LDH, CK-MB and cardiac troponin in the serum were also revealed to be significantly increased in the CCM8 group. Additionally, the levels of IL-1 and IL-6 in both serum and myocardial tissues were significantly increased in rats in the CCM8 group. However, the levels of IL-2 in both serum and myocardial tissues were decreased, which were observed alongside reductions in myocardial β1 and M2 receptor protein expression in the myocardial tissues. Taken together, these results indicate that inflammatory factors may be involved in mediating damage to the myocardium in rats with cirrhosis. During cirrhosis-induced cardiac dysfunction, there may exist a mechanism for downregulation of autonomic nerve system. PMID:34373726 | PMC:PMC8343770 | DOI:10.3892/etm.2021.10472 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Ellagic acid inhibits high glucose-induced injury in rat mesangial cells via the PI3K/Akt/FOXO3a signaling pathway

xlomafota13 shared this article with you from Inoreader Ellagic acid inhibits high glucose-induced injury in rat mesangial cells via the PI3K/Akt/FOXO3a signaling pathway Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):1017. doi: 10.3892/etm.2021.10449. Epub 2021 Jul 15. ABSTRACT The pathological damage of mesangial cells serves an important role in the occurrence and development of diabetic nephropathy. Ellagic acid has been reported to possess antioxidant, antitumor, antiviral and anti-inflammatory properties in several diseases, but the roles of ellagic acid in diabetic nephropathy are unclear. The main aim of the present study was to investigate the effect of ellagic acid on high glucose-induced mesangial cell damage. The results revealed that high glucose could induce the hyperproliferation of mesangial cells, decrease the activity of superoxide dismutase, increase the malondialdehyde content, the level of reactive oxygen species, the secretion of inflammatory factors (TNF-α, IL-1β and IL-6) and the synthesis of extracellular matrix (Fibronectin, MMP-9 and TIMP-1) and activate the PI3K/Akt/FOXO3a signaling pathway. Ellagic acid could attenuate the injury of mesangial cells induced by high glucose in a concentration-dependent manner and its effect was consistent with that of a PI3K inhibitor (LY294002). Moreover, a PI3K agonist (740Y-P) reversed the protective effect of ellagic acid on mesangial cells induced by high glucose. In conclusion, ellagic acid protected mesangial cells from high glucose-induced injury in a concentration-dependent manner. The mechanism may be associated with ellagic acid inhibiting the activation of the PI3K/Akt signaling pathway and reducing the expression levels of downstream transcription factor FOXO3a. PMID:34373703 | PMC:PMC8343806 | DOI:10.3892/etm.2021.10449 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

MicroRNA-934 promotes colorectal cancer cell proliferation by directly targeting Dickkopf-related protein 2

xlomafota13 shared this article with you from Inoreader MicroRNA-934 promotes colorectal cancer cell proliferation by directly targeting Dickkopf-related protein 2 Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):1041. doi: 10.3892/etm.2021.10473. Epub 2021 Jul 21. ABSTRACT Increasing evidence demonstrates that dysregulation of microRNAs (miRNAs/miRs) is implicated in the development of colorectal cancer. However, the biological functions of several differentially expressed miRNAs remain unknown. In the present study, a bioinformatic analysis of a previously published microarray data and reverse transcription-quantitative PCR analysis demonstrated that miR-934 expression was upregulated in colorectal cancer samples collected from patients. Mechanistically, Dickkopf-related protein 2 (DDK2) was identified as a novel target gene of miR-934 in colorectal cancer cells. Knockdown of DDK2 reversed the inactivation of Wnt signaling pathway induced using miR-934 inhibitor in colorectal cancer cells. In addition, DDK2 silencing reversed miR-934 inhibitor-induced cell proliferation inhibition and elevation of cell apoptosis. The results demonstrated that DDK2 mRNA expression was negatively associated with miR-934 expression in colorectal tumors. Collectively, the results of the present study demonstrated that the miR-934/DDK2 axis regulated colorectal cancer cell proliferation, suggesting that miR-934 may be a biomarker for patients with colorectal cancer. PMID:34373727 | PMC:PMC8343583 | DOI:10.3892/etm.2021.10473 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Lidocaine liposome modified with folic acid suppresses the proliferation and motility of glioma cells via targeting the PI3K/AKT pathway

xlomafota13 shared this article with you from Inoreader Lidocaine liposome modified with folic acid suppresses the proliferation and motility of glioma cells via targeting the PI3K/AKT pathway Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):1025. doi: 10.3892/etm.2021.10457. Epub 2021 Jul 15. ABSTRACT Glioma is life-threatening tumor of the central nervous system. Although lidocaine is usually used as local anesthetic, it also has antitumor effects. However, its clinical application in glioma is hampered by limited distribution to the brain. The aim of the present study was to enhance the ability of lidocaine to penetrate the blood-brain barrier (BBB) to target glioma and investigate its antitumor mechanism. A folic acid (FA)-modified lidocaine-carrying liposome (Lid-FA-Lip) was prepared, and its particle size, ζ potential, encapsulation efficiency, release profile stability and hemolytic effect were characterized in vitro. The targeting capacity and antitumor activities of Lid-FA-Lip were also investigated in vitro and in vivo. The results indicated that the modification of liposomes with FA significantly improved the ab ility of lidocaine to cross the BBB in an in vitro model and increased its uptake by U87 cells. Additionally, Lid-FA-Lip significantly suppressed the motility of U87 glioma cells and stimulated apoptosis. Furthermore, the results confirmed that Lid-FA-Lip targeted the PI3K/AKT pathway and suppressed the growth of glioma xenografts in mice. In summary, the study demonstrated that Lid-FA-Lip is a promising liposomal formulation of lidocaine that may provide improved therapeutic effects on glioma, mediated via the PI3K/AKT pathway. PMID:34373711 | PMC:PMC8343891 | DOI:10.3892/etm.2021.10457 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.