Prognostic value of MTA1, SOX4 and EZH2 expression in esophageal squamous cell carcinoma

xlomafota13 shared this article with you from Inoreader Prognostic value of MTA1, SOX4 and EZH2 expression in esophageal squamous cell carcinoma Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):722. doi: 10.3892/etm.2021.10154. Epub 2021 May 3. ABSTRACT Esophageal cancer has always been one of the major malignant tumor types affecting the health of the Chinese population. Metastasis-associated protein 1 (MTA1), SOX4 and enhancer of zeste homolog 2 (EZH2) are all potent inducers of invasion and metastasis in esophageal squamous cell carcinoma (ESCC). However, the role of these signaling molecules and their implication in ESCC have remained largely elusive. In the present study, the effects of MTA1, SOX4 and EZH2 on the prognosis of patients with ESCC were explored. Immunohistochemistry was used to examine the expression levels of MTA1, SOX4 and EZH2. The χ2 test was used to analyze the association between protein expression and clinicopathological parameters. Kaplan-Meier curves and Cox proportional hazards model survival analysis was performed to investigate the effects of the three pr oteins examined on disease prognosis. The results indicated that MTA1 may be used as a prognostic and diagnostic marker for ESCC. To the best of our knowledge, the present study was the first to demonstrate that MTA1-SOX4 signaling is associated with prognosis in ESCC. However, no significant association was noted between SOX4 and EZH2 in the present study, which was inconsistent with previously reported findings. The function of the MTA1-SOX4-EZH2 axis and the interactions of the proteins involved require further investigation. PMID:34007331 | PMC:PMC8120658 | DOI:10.3892/etm.2021.10154 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Morphine enhances LPS-induced macrophage apoptosis through a PPARγ-dependent mechanism

xlomafota13 shared this article with you from Inoreader Morphine enhances LPS-induced macrophage apoptosis through a PPARγ-dependent mechanism Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):714. doi: 10.3892/etm.2021.10146. Epub 2021 May 3. ABSTRACT Morphine has been widely used for the treatment of pain and extensive studies have revealed a regulatory role for morphine in cell apoptosis. However, the molecular mechanisms underlying morphine-mediated apoptosis remain to be fully elucidated. The present study aimed to investigate the effects of morphine on lipopolysaccharide (LPS)-induced bone marrow-derived macrophage (BMDM) apoptosis and to determine the role of the peroxisome proliferator-activated receptor (PPAR)γ signaling pathway in this process. BMDMs were isolated from BALB/c mice and stimulated with LPS. Hoechst 33342 staining and flow cytometric analysis were performed to evaluate the effects of morphine on LPS-induced apoptosis of BMDMs. Caspase activity assays were used to determine the involvement of the apoptosis pathway. The expression levels of caspase-3, caspase-8, caspase-9 a nd PPARγ were analyzed using western blotting. Finally, GW9662, a specific PPARγ antagonist, was used to determine whether the regulatory effects of morphine on LPS-induced BMDM apoptosis were PPARγ-dependent. The results of the present study revealed that morphine increased the apoptosis of LPS-stimulated BMDMs. Morphine upregulated the expression levels and activity of caspase-3 in LPS-stimulated BMDMs, but downregulated the expression levels and activity of caspase-8. Morphine treatment also upregulated LPS-induced PPARγ expression levels in BMDMs. Finally, the stimulatory effects of morphine on LPS-induced apoptosis and caspase-3/9 activation were markedly reduced by GW9662. In conclusion, the findings of the present study indicated that morphine significantly promoted LPS-induced BMDM apoptosis and caspase-3/9 activation. These results suggested that the intrinsic pathway of apoptosis may be involved in the proapoptotic effects of morphine on LPS-stimulated BMDMs, which may be dependent, at least partially, on PPARγ activation. PMID:34007323 | PMC:PMC8120503 | DOI:10.3892/etm.2021.10146 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Histone demethylase KDM2A: Biological functions and clinical values (Review)

xlomafota13 shared this article with you from Inoreader Histone demethylase KDM2A: Biological functions and clinical values (Review) Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):723. doi: 10.3892/etm.2021.10155. Epub 2021 May 4. ABSTRACT Histone lysine demethylation modification is a critical epigenetic modification. Lysine demethylase 2A (KDM2A), a Jumonji C domain-containing demethylase, demethylates the dimethylated H3 lysine 36 (H3K36) residue and exerts little or no activity on monomethylated and trimethylated H3K36 residues. KDM2A expression is regulated by several factors, such as microRNAs, and the phosphorylation of KDM2A also plays a vital role in its function. KDM2A mainly recognizes the unmethylated region of CpG islands and subsequently demethylates histone H3K36 residues. In addition, KDM2A recognizes and binds to phosphorylated proteins, and promotes their ubiquitination and degradation. KDM2A plays an important role in chromosome remodeling and gene transcription, and is involved in cell proliferation and differentiation, cell metabolism, heterochromosomal homeostas is and gene stability. Notably, KDM2A is crucial for tumorigenesis and progression. In the present review, the documented biological functions of KDM2A in physiological and pathological processes are comprehensively summarized. PMID:34007332 | PMC:PMC8120640 | DOI:10.3892/etm.2021.10155 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Overexpression of ING3 is associated with attenuation of migration and invasion in breast cancer

xlomafota13 shared this article with you from Inoreader Overexpression of <em>ING3</em> is associated with attenuation of migration and invasion in breast cancer Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):699. doi: 10.3892/etm.2021.10131. Epub 2021 May 2. ABSTRACT Inhibitor of growth 3 (ING3) has been identified as a potential cancer drug target, but little is known about its role in breast cancer. Thus, the present study aimed to investigate ING3 expression in breast cancer, its clinical value, and how ING3 influences the migration and invasion of breast cancer cells. The Cancer Genome Atlas and UALCAN databases were used to analyze ING3 expression in cancer tissues and normal tissues. Survival analysis was performed using the UALCAN, UCSC Xena and KM-plot databases. In addition, reverse transcription-quantitative PCR and western blot analyses were performed to detect ING3 mRNA and protein expression levels. ING3 was overexpressed via lentiviral vector transfection, while the Transwell and wound healing assays were performed to assess the cell migratory and invasive abilities. Protein i nteraction and pathway analyses were performed using the GeneMANIA and Kyoto Encyclopedia of Genes and Genomes databases, respectively. The results demonstrated that ING3 expression was significantly lower in cancer tissues compared with normal tissues (P<0.05). In addition, luminal A and human epidermal growth factor receptor 2 (HER2)-enriched breast cancer tissues expressed lower levels of ING3 compared with normal breast tissues. Notably, statistically significant differences were observed in long-term survival between patients with luminal A (P=0.04) and HER2-enriched (P=0.008) breast cancer, with high and low expression levels of ING3. The results of the Transwell migration and invasion assays demonstrated that overexpression of ING3 significantly inhibited the migratory and invasive abilities of MCF7 (P<0.05) and HCC1937 (P<0.05) cells. The results of the wound healing assay demonstrated that the percentage wound closure significantly decreased in cells transfected with LV5-ING3 compared with the negative control group at 12 h (P<0.05) and 24 h (P<0.01). The PI3K/AKT, JAK/STAT, NF-κB and Wnt/β-catenin pathways are the potential pathways regulated by ING3. Notably, overexpression of ING3 inhibited migration and invasion in vitro. However, further studies are required to determine whether ING3 regulates the biological behavior of breast cancer via tumor-related pathways. PMID:34007308 | PMC:PMC8120550 | DOI:10.3892/etm.2021.10131 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Changes in NSE and S-100β during the perioperative period and effects on brain injury in infants with biliary atresia undergoing parent donor liver transplantation

xlomafota13 shared this article with you from Inoreader Changes in NSE and S-100β during the perioperative period and effects on brain injury in infants with biliary atresia undergoing parent donor liver transplantation Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):724. doi: 10.3892/etm.2021.10156. Epub 2021 May 4. ABSTRACT The present study aimed to investigate the effects of parental donor liver transplantation on the perioperative changes of serum calcium-binding protein β (S-100β) and neuron-specific enolase (NSE) levels, two markers of brain injury, and on postoperative cognitive function. The present study was a prospective observational study of infants with congenital biliary atresia who underwent selective liver transplantation in 2017 at Tianjin First Central Hospital (Tianjin, China). Blood samples were collected prior to, during and following surgery, and S-100β and NSE levels were measured using ELISA. The pediatric patients were assessed using the Bayley Scales of Infant Development 1 day prior to and 3 months after surgery. Additionally, the pediatric anesthesia emergence delirium scores were evaluated. The results demonstrated that serum NSE and S10 0β were increased during and after surgery compared with prior to surgery (P<0.05). Furthermore, serum S-100β and NSE levels peaked 1 h after the neohepatic phase compared with prior to surgery (P<0.05). Compared with 1 day before surgery, mental development index (MDI) and psychomotor development index (PDI) were decreased 3 months after surgery (MDI, 87.7±8.4 vs. 84.5±8.5, P=0.015; PDI, 82.9±8.7 vs. 79.6±8.8, P=0.016). In conclusion, parental donor liver transplantation may cause a certain degree of brain injury in pediatric patients with end-stage liver disease, as revealed by increased serum NSE and S100β levels. PMID:34007333 | PMC:PMC8120510 | DOI:10.3892/etm.2021.10156 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

MTHFD2 facilitates breast cancer cell proliferation via the AKT signaling pathway

xlomafota13 shared this article with you from Inoreader MTHFD2 facilitates breast cancer cell proliferation via the AKT signaling pathway Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):703. doi: 10.3892/etm.2021.10135. Epub 2021 May 2. ABSTRACT MTHFD2 is a folate-coupled mitochondrial metabolic enzyme which has been extensively studied in breast cancer; however, its molecular functions in this cancer remain unclear. The current study aimed to reveal the underlying mechanism of breast cancer. MTHFD2 expression status and prognostic value were determined using the Gene Expression Profiling Interactive Analysis database. To determine the function of MTHFD2 in breast cancer, MCF-7 cells with stable overexpression of Flag-MTHFD2 or depletion of MTHFD2 were generated. Cell Counting Kit-8 and colony formation assays were used to examine the effect of MTHFD2 overexpression or knockout on MCF-7 cell proliferation and clonogenicity, respectively. Luciferase reporter and an AKT inhibitor (GSK6906) analysis were carried out to investigate the effect of MTHFD2 on the AKT signaling pathway. The results demonstrated that MTHFD2 expression level was higher in breast cancer tissues compared with adjacent normal tissues. Furthermore, patients with high MTHFD2 expression had significantly poorer overall survival compared with patients with low MTHFD2 expression. In addition, ectopic expression of MTHFD2 promoted the tumorigenic properties of MCF-7 cells, including proliferation and clonogenicity. Conversely, depletion of MTHFD2 had the opposite effect on the malignant properties of MCF-7 cells. Luciferase reporter demonstrated that MTHFD2 can significantly increase the ATK luciferase density. Furthermore, the Akt inhibitor GSK690693 significantly decreased the increased clonogenicity caused by MTHFD2 overexpression in MCF-7 cells. Taken together, the findings from the present study suggested that MTHFD2 may serve a protumor role in the malignancy of breast cancer by activating the AKT signaling pathway. These results provide an alternative theoretical foundation that could help the de velopment of MTHFD2-targeted breast cancer treatment. PMID:34007312 | PMC:PMC8120508 | DOI:10.3892/etm.2021.10135 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Spontaneous bacterial peritonitis mortality trends of cirrhotic patients in the last decade in Constanta County

xlomafota13 shared this article with you from Inoreader Spontaneous bacterial peritonitis mortality trends of cirrhotic patients in the last decade in Constanta County Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):732. doi: 10.3892/etm.2021.10164. Epub 2021 May 7. ABSTRACT Spontaneous bacterial peritonitis (SBP) is a complication of liver cirrhosis with an increased in-hospital mortality rate. For this reason, the aim of the present study was to examine the main predictors of mortality in order to be able to identify high-risk patients in time and to guide the optimal treatment for prognosis improvement. We retrospectively collected demographic, clinical, laboratory and treatment data as well as data regarding length of stay and cost of hospitalization from 72 patients diagnosed with SBP between January 2010 and December 2019 in the Emergency Clinical Hospital St. Apostle Andrew, Constanta, Romania. Patients were divided into two groups: Those who survived and those who died. Logistic regression was used to identify a possible association between these factors and the increased risk of mortality. Univariate analysis revealed that clinical factors (fever, chills, and hepatic encephalopathy), biological factors such as serum and ascites leukocyte value, polymorphonuclear percentage (PMN), erythrocyte sedimentation rate (ESR) value, previous SBP episodes, and the presence of complications such as acute kidney injury (AKI), sepsis, and systemic inflammatory response syndrome (SIRS) were significantly associated with in-hospital mortality in patients with SBP. Multivariate analysis revealed that SIRS (P=0.0010) and fever (P=0.0258) were significantly associated with in-hospital mortality in patients with SBP. Findings of the present study suggest that, SIRS and fever were independent predictive factors of mortality in cirrhotic patients with SBP. PMID:34007340 | PMC:PMC8120657 | DOI:10.3892/etm.2021.10164 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Abnormal expression of miR-135a in patients with depression and its possible involvement in the pathogenesis of the condition

xlomafota13 shared this article with you from Inoreader Abnormal expression of miR-135a in patients with depression and its possible involvement in the pathogenesis of the condition Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):726. doi: 10.3892/etm.2021.10158. Epub 2021 May 4. ABSTRACT At present, due to the increasing pressures on society and the stress of everyday living, the number of individuals suffering from depression has increased. Therefore, the treatment of depression has also received increasing attention. MicroRNA (miRNA/miR)-135a is a well-studied miRNA. It has been reported that miR-135a is significantly downregulated in patients with depression and may be a potential marker for the diagnosis of the condition. However, the specific mechanisms of action of miR-135a in patients with depression remain unclear. In the present study, it was found that miR-135a was downregulated in patients with depression, and in a mouse model of depression. The effects of miR-135a on depression-related symptoms in mice were then explored. In the mice with chronic unpredictable mild stress (CUMS) that were treated with miR-135a for 3 wee ks, a significantly reduced level of weight gain was observed in comparison with the control group. In addition, treatment with miR-135a mimic significantly increased sucrose preference in the sucrose preference test in the mice, and reduced the immobility time in the forced swimming test and tail suspension test. Treatment with miR-135a mimic also inhibited CUMS-induced hippocampal cell apoptosis. Furthermore, treatment with miR-135a mimic and fluoxetine significantly reduced the CUMS-induced increase in the expression levels of inflammatory factors (IL-1β, IL-6 and TNF-α) in the hippocampus of the mice. Subsequently, reverse transcription-quantitative polymerase chain reaction and western blot analysis revealed that treatment with miR-135a mimic significantly inhibited the expression of Toll-like receptor 4 in the mouse hippocampus. In conclusion, the findings of the present study indicate that miR-135a may be a novel potential target for the treatment of depression. PMID: 34007335 | PMC:PMC8120643 | DOI:10.3892/etm.2021.10158 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Targeted inhibition of STAT3 in neural stem cells promotes neuronal differentiation and functional recovery in rats with spinal cord injury

xlomafota13 shared this article with you from Inoreader Targeted inhibition of STAT3 in neural stem cells promotes neuronal differentiation and functional recovery in rats with spinal cord injury Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):711. doi: 10.3892/etm.2021.10143. Epub 2021 May 3. ABSTRACT STAT3 is expressed in neural stem cells (NSCs), where a number of studies have previously shown that STAT3 is involved in regulating NSC differentiation. However, the possible molecular mechanism and role of STAT3 in spinal cord injury (SCI) remain unclear. In the present study, the potential effect of STAT3 in NSCs was first investigated by using short hairpin RNA (shRNA)-mediated STAT3 knockdown in rat NSCs in vitro. Immunofluorescence of β3-tubulin and glial fibrillary acidic protein staining and western blotting showed that knocking down STAT3 expression promoted NSC neuronal differentiation, where the activity of mTOR was upregulated. Subsequently, rats underwent laminectomy and complete spinal cord transection followed by transplantation of NSCs transfected with control-shRNA or STAT3-shRNA at the injured site in vivo. Spinal c ord-evoked potentials and the Basso-Beattie-Bresnahan scores were used to examine functional recovery. In addition, axonal regeneration and tissue repair were assessed using retrograde tracing with FluoroGold, hematoxylin and eosin, Nissl and immunofluorescence staining of β3-tubulin, glial fibrillary acidic protein and microtubule-associated protein 2 following SCI. The results showed that transplantation with NSCs transfected with STAT3-RNA enhanced functional recovery following SCI and promoted tissue repair in rats, in addition to improving neuronal differentiation of the transplanted NSCs in the injury site. Taken together, in vitro and in vivo evidence that inhibiting STAT3 could promote NSC neuronal differentiation was demonstrated in the present study. Therefore, transplantation with NSCs with STAT3 expression knocked down appears to hold promising potential for enhancing the benefit of NSC-mediated regenerative cell therapy for SCI. PMID:34007320 | PMC:PMC8120646 | DOI:10.3892/etm.2021.10143 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Efficacy of percutaneous vertebroplasty for the relief of osteoblastic spinal metastasis pain

xlomafota13 shared this article with you from Inoreader Efficacy of percutaneous vertebroplasty for the relief of osteoblastic spinal metastasis pain Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):727. doi: 10.3892/etm.2021.10159. Epub 2021 May 4. ABSTRACT The aim of the present manuscript was to retrospectively evaluate the efficacy of fluoroscopy-guided percutaneous vertebroplasty (PVP) for the relief of osteoblastic spinal metastases pain. PVP was performed in 39 consecutive patients with 82 osteoblastic metastatic spinal vertebras. 19 vertebras had pathologic compressive fracture and the other 63 vertebras had no compressive fracture with obvious imaging abnormalities. The ages of the patients ranged from 40 to 77 years with a mean age of 58.5±9.0 years. Visual analog scale (VAS) and QLQ-BM22 score were used to evaluate pain and quality of life at 2 days pre-operation and at 1 week and 3 months post-operation. Among all 82 vertebras, 35 vertebras had been injected bilaterally and the other 47 vertebras unilaterally. The amount of cement injected per lesion ranged from 0.5 to 4.5 ml with a mean v olume of 1.6±0.8 ml. Cement deposition in all lesions was uniform. The patients were followed up from 3 to 15.5 months with a mean follow up time of 5.6±3.4 months. Mean VAS score declined significantly from preoperative 4.3±2.4 to postoperative 3.0±1.7 at 1 week and 2.4±2.0 at 3 months after the procedure (P=0.001). Mean QLQ-BM22 score declined significantly from preoperative 49.1±12.3 to postoperative 42.4±9.5 at 1 week and 39.6±10.4 at 3 months after the procedure (P<0.001). Extraosseous cement leakage occurred in 21 vertebras of 13 cases and in 1 case into the thoracic vertebra canal without causing any clinical complications. No further procedures were performed after leakage. PVP is an effective treatment for painful osteoblastic spinal metastases. It can relieve pain, reduce disability and improve function. The main complications are bone cement leakage and incomplete pain relief. PMID:34007336 | PMC:PMC8120652 | DOI:10.3892/etm.2021.10159 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.