Prognostic value of microRNA-378 in esophageal cancer and its regulatory effect on tumor progression

xlomafota13 shared this article with you from Inoreader Prognostic value of microRNA-378 in esophageal cancer and its regulatory effect on tumor progression Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):704. doi: 10.3892/etm.2021.10136. Epub 2021 May 2. ABSTRACT The incidence and mortality rates of esophageal squamous cell carcinoma (ESCC) are high in China, which has increased the clinical and economic burden. The present study aimed to investigate the role of microRNA (miRNA/miR)-378 in ESCC. Reverse transcription-quantitative polymerase chain reaction analysis was performed to detect miR-378 expression in ESCC tissues and cell lines. Survival analysis was performed using the Kaplan-Meier method, while Cox regression analysis was performed to determine the prognostic value of miR-378 in ESCC. miR-378 mimic and miR-378 inhibitor was transfected into ESCC cells to overexpress or knockdown miR-378 expression levels in ESCC cells. The Cell Counting Kit-8 assay was performed to assess the proliferative ability of ESCC cells, while the Transwell assay was conducted to assess the effect of miR-378 on the migrat ory and invasive abilities of ESCC cells. The results demonstrated that miR-378 displayed significantly lower expression both in ESCC cells and tissues by comparison with those in normal cells and adjacent tissues. In addition, patients with low miR-378 expression had a worse prognosis and a shorter overall survival time than those with high miR-378 expression. Furthermore, low miR-378 expression promoted ESCC cell proliferation, migration and invasion. Taken together, the results of the present study suggest that miR-378 may act as a tumor suppressor in the occurrence and development of ESCC. PMID:34007313 | PMC:PMC8120653 | DOI:10.3892/etm.2021.10136 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Chrysoeriol ameliorates COX-2 expression through NF-κB, AP-1 and MAPK regulation via the TLR4/MyD88 signaling pathway in LPS-stimulated murine macrophages

xlomafota13 shared this article with you from Inoreader Chrysoeriol ameliorates COX-2 expression through NF-κB, AP-1 and MAPK regulation via the TLR4/MyD88 signaling pathway in LPS-stimulated murine macrophages Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):718. doi: 10.3892/etm.2021.10150. Epub 2021 May 3. ABSTRACT Chrysoeriol is a flavonoid that has diverse biological properties, including antioxidation, anti-inflammation, chemoprevention and immunomodulation. Despite its reported anti-inflammatory activity, the exact underlying molecular mechanism has not yet been elucidated. In the current study, the anti-inflammatory mechanism of chrysoeriol involving lipopolysaccharide (LPS)-induced cyclooxygenase-2 (COX-2) and its upstream signaling molecules was investigated in RAW 264.7 cells. The mechanism was evaluated via ELISA and western blotting assays. Chrysoeriol significantly inhibited LPS-induced prostaglandin E2 (PGE2) production and COX-2 expression without cytotoxicity. Activated transcription factors that further induced the inflammation response, including nuclear factor (NF)-κB and activator protein-1 (AP-1), were significantly a ttenuated by chrysoeriol treatment. Furthermore, LPS-induced phosphorylation levels of phosphoinositide-3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK) were abolished by chrysoeriol treatment, which was confirmed by selective inhibitors. Additionally, chrysoeriol significantly inhibited the LPS-induced activation of adaptor molecules in RAW 264.7 cells, including toll-like receptor 4 (TLR4) and myeloid differentiation primary response 88. Therefore, the results suggested that chrysoeriol ameliorates TLR4-mediated inflammatory responses by inhibiting NF-κB and AP-1 activation as well as suppressing PI3K/Akt and MAPK phosphorylation in LPS-stimulated RAW 264.7 cells. PMID:34007327 | PMC:PMC8120564 | DOI:10.3892/etm.2021.10150 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Fatty acids and their role in type-2 diabetes (Review)

xlomafota13 shared this article with you from Inoreader Fatty acids and their role in type-2 diabetes (Review) Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):706. doi: 10.3892/etm.2021.10138. Epub 2021 May 2. ABSTRACT Age, lifestyle and diet are major risk factors for the onset of type 2 diabetes mellitus (T2DM). Insulin resistance (IR) and β-cell dysfunction underlie the pathophysiology of T2DM. Diabetic populations are also prone to lipid and lipoprotein abnormalities as an indirect effect of IR on key metabolic enzymes. However, recent studies suggested that lipid changes may not only be a consequence of impaired glucose metabolism but also a causative factor. Fatty acids (FAs) influence translocation of glucose transporters and insulin receptor binding and signalling, in addition to cell membrane fluidity and permeability. It is thus suggested that FAs may have an essential role in the development of IR and T2DM. Specific combinations of FAs within phospholipids and triglycerides were indicated to exhibit the strongest associations with the risk of T2DM. Th e aim of the present review was to investigate the role of FAs in the pathogenesis of T2DM, as it has yet to be fully elucidated. PMID:34007315 | PMC:PMC8120551 | DOI:10.3892/etm.2021.10138 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Effect of DNA methylation on gene transcription is associated with the distribution of methylation sites across the genome in osteoarthritis

xlomafota13 shared this article with you from Inoreader Effect of DNA methylation on gene transcription is associated with the distribution of methylation sites across the genome in osteoarthritis Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):719. doi: 10.3892/etm.2021.10151. Epub 2021 May 3. ABSTRACT Genetics and epigenetics are important subjects in the field of osteoarthritis (OA) research. DNA methylation may affect gene transcription, but the specific mechanisms have remained to be fully elucidated. In the present study, the ChAMP methylation analysis package was used to identify differentially methylated genes (DMGs) from the dataset GSE63695 from the Gene Expression Omnibus (GEO) database. The distribution of differentially methylated sites (DMS) and the total array sites across the genome were analyzed by enrichment analysis. Subsequently, two mRNA expression profiling datasets, GSE114007 and GSE113825, were obtained from the GEO database and common differentially expressed genes (DEGs) were identified using the Limma package. Key genes were screened by analyzing the distribution of DMS across the genome consisting of DEGs and DMGs. A to tal of 1,662 and 1,986 DEGs were identified between OA and normal human cartilage from the GSE113825 and GSE114007 dataset, respectively. A further screening revealed 292 genes with common differences between the two datasets. A total of 574 DMS containing 394 DMGs were observed between OA and normal cartilage. Integrative analysis revealed a corresponding subset of 15 genes. Of these, 6 genes were verified by reverse transcription-quantitative PCR, confirming that the mRNA expression of 5 genes (MAP1B, FNDC1, ANLN, SCNN1A and STC2) in OA cartilage was consistent with the mRNA expression from the analysis of the datasets. Upon treatment with the DNA methylation inhibitor 5-aza-2'-deoxycytidine, the mRNA levels of FNDC1 and SCNN1A were decreased, and no significant alteration in the mRNA levels of MAP1B, ANLN, KCNN4 and STC2 was observed. The incidence of differential methylation varied in subregions of the genome and the effects on transcription were associated with the distribution of DEGs across the genome. The regulation of this appears more complex than initially postulated. Combining the data on epigenetic differences of OA with the genome or transcriptome data for analysis may improve the understanding of the pathophysiological processes of OA. FNDC1 and SCNN1A may potentially be valuable biomarkers for OA. PMID:34007328 | PMC:PMC8120505 | DOI:10.3892/etm.2021.10151 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Klotho alleviates chronic intermittent hypoxia-induced genioglossus myocyte apoptosis by inhibiting endoplasmic reticulum stress

xlomafota13 shared this article with you from Inoreader Klotho alleviates chronic intermittent hypoxia-induced genioglossus myocyte apoptosis by inhibiting endoplasmic reticulum stress Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):708. doi: 10.3892/etm.2021.10140. Epub 2021 May 2. ABSTRACT Chronic intermittent hypoxia (CIH) has been shown to induce cell apoptosis in multiple organs of the human body. The present study aimed to assess the effects of exogenous klotho on CIH-induced genioglossus muscle injury, as well as the involvement of endoplasmic reticulum stress (ERS) in this process. A total of 36 adult C57BL/6 male mice were assigned to normoxia control (NC), CIH and CIH + klotho groups (n=12 mice/group). ELISA was performed to detect the level of klotho protein in the serum and in the genioglossus muscle tissue samples. Apoptosis was evaluated using the TUNEL assay. Reactive oxygen species (ROS) levels were quantified using a dihydroethidium assay kit, and the protein and mRNA levels of ERS-associated proteins (namely, glucoseregulated protein 78, C/EBP homologous protein, cleaved caspase-12 and cleaved caspase-3) in geniogloss us samples were assessed using immunoblot assay and reverse transcription-quantitative PCR, respectively. Compared with the NC group, the quantities of klotho protein in the serum and genioglossus muscle tissue samples in the CIH group were significantly decreased, whereas the apoptotic rate, ROS levels and protein and mRNA levels of the ERS-associated proteins in the genioglossus muscle were significantly increased. Following supplementation with exogenous klotho protein, the klotho protein levels in the serum and genioglossus muscle tissue of mice were found to be markedly increased, and the apoptotic rate, ROS levels and protein and mRNA levels of the ERS-associated proteins in the genioglossus muscle were decreased compared with those in the CIH group. Taken together, the results of the present study have demonstrated that exogenous klotho may inhibit apoptosis of genioglossus myocytes in mice by inhibiting ROS-associated ERS. PMID:34007317 | PMC:PMC8120644 | DOI:10.3892/etm.2021.10140 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Inhibition of Gabrp reduces the differentiation of airway epithelial progenitor cells into goblet cells

xlomafota13 shared this article with you from Inoreader Inhibition of Gabrp reduces the differentiation of airway epithelial progenitor cells into goblet cells Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):720. doi: 10.3892/etm.2021.10152. Epub 2021 May 3. ABSTRACT Bronchial asthma is an intractable pulmonary disease that affects millions of individuals worldwide, with the overproduction of mucus contributing to high morbidity and mortality. Gamma-aminobutyric acid (GABA) is associated with goblet cell hyperplasia in the lungs of primate models and Club cells serve as airway epithelial progenitor cells that may differentiate into goblet and ciliated cells. In the present study, it was investigated whether the GABAA receptor pi (Gabrp) is essential for Club cell proliferation and differentiation in mice. Validation of microarray analysis results by reverse transcription-quantitative PCR (RT-qPCR) demonstrated that Gabrp is highly expressed in mouse Club cells. Predominant expression of Gabrp in mouse Club cells was further confirmed based on naphthalene-induced Club cell injury in mice, with organoid cultures indicating significant reductions in the organoid-forming ability of mouse Club cells in the presence of Gabrp antagonist bicuculline methiodide (BMI). Furthermore, the RT-qPCR results indicated that the mRNA levels of chloride channel accessory 3, pseudogene (Clca3p), mucin (Muc)5Ac and Muc5B were significantly decreased in BMI organoid cultures. These results suggested that blocking GABA signaling through Gabrp inhibits mouse Club cell proliferation, as well as differentiation into goblet cells. Therefore, targeting GABA/Gabrp signaling may represent a promising strategy for treating goblet cell hyperplasia in bronchial asthma. PMID:34007329 | PMC:PMC8120639 | DOI:10.3892/etm.2021.10152 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Autophagy-related signaling pathways are involved in cancer (Review)

xlomafota13 shared this article with you from Inoreader Autophagy-related signaling pathways are involved in cancer (Review) Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):710. doi: 10.3892/etm.2021.10142. Epub 2021 May 3. ABSTRACT Autophagy is a self-digestion process in cells that can maintain energy homeostasis under normal circumstances. However, misfolded proteins, damaged mitochondria and other unwanted components in cells can be decomposed and reused via autophagy in some specific cases (including hypoxic stress, low energy states or nutrient deprivation). Therefore, autophagy serves a positive role in cell survival and growth. However, excessive autophagy may lead to apoptosis. Furthermore, abnormal autophagy may lead to carcinogenesis and promote tumorigenesis in normal cells. In tumor cells, autophagy may provide the energy required for excessive proliferation, promote the growth of cancer cells, and evade apoptosis caused by certain treatments, including radiotherapy and chemotherapy, resulting in increased treatment resistance and drug resistance. On the other han d, autophagy leads to an insufficient nutrient supply in cancer cells and the destruction of energy homeostasis, thereby inducing cancer cell apoptosis. Therefore, understanding the mechanism of the double-edged sword of autophagy is crucial for the treatment of cancer. The present review summarizes the signaling pathways and key factors involved in autophagy and cancer to provide possible strategies for treating tumors. PMID:34007319 | PMC:PMC812065 0 | DOI:10.3892/etm.2021.10142 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Contrast-enhanced ultrasound molecular imaging of activated platelets in the progression of atherosclerosis using microbubbles bearing the von Willebrand factor A1 domain

xlomafota13 shared this article with you from Inoreader Contrast-enhanced ultrasound molecular imaging of activated platelets in the progression of atherosclerosis using microbubbles bearing the von Willebrand factor A1 domain Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):721. doi: 10.3892/etm.2021.10153. Epub 2021 May 3. ABSTRACT Platelet-endothelial interactions have been linked to increased inflammatory activation and a prothrombotic state in atherosclerosis. The interaction between von Willebrand factor (vWF)-A1 domain and platelet glycoprotein (GP) Ib/IX plays a significant role in mediating the adhesion of platelets to the injured endothelium. In the present study, contrast-enhanced ultrasound (CEU) molecular imaging with microbubbles bearing the vWF-A1 domain was performed to non-invasively monitor activated platelets on the vascular endothelium in the procession of atherosclerosis. A targeted CEU contrast agent was prepared by attaching the vWF-A1 domain to the shell of microbubbles (MbA1). Rat isotype control antibody was used to produce control (Mbctrl) microbubbles. The binding of MbA1 and Mbctrl to activated platelets w as assessed in in vitro flow chamber experiments. Apolipoprotein E (ApoE-/-) deficient mice were studied as a model of atherosclerosis. At 8, 16 and 32 weeks of age, CEU molecular imaging of the proximal aorta with MbA1 and Mbctrl was performed and the imaging signals from microbubbles were quantified. Atherosclerotic lesion severity and platelets on the endothelial surface were assessed by histology and immunohistochemistry. In in vitro flow chamber studies, attachment of MbA1 to activated platelets on culture dishes was significantly greater than that of Mbctrl across a range of shear stresses (P<0.05). The attachment of Mbctrl was sparse and not related to the aggregated platelets. As lesion development progressed in the ApoE-/- mice, molecular imaging of activated platelets demonstrated selective signal enhancement of MbA1 (P<0.05 vs. Mbctrl) at all ages. Select ive signal enhancement from MbA1 increased from 8 to 32 weeks of age. Immunohistochemistry for GPIIb revealed the presence of platelets on the endothelial cell surface in each group of ApoE-/- mice and that the degree of platelet deposits was age-dependent. The results of the present study indicated that non-invasive CEU molecular imaging with targeted microbubbles bearing the vWF-A1 domain could not only detect activated platelets on the vascular endothelium but also indicate lesion severity in atherosclerosis. PMID:34007330 | PMC:PMC8120515 | DOI:10.3892/etm.2021.10153 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Tolerogenic dendritic cells suppress titanium particle-induced inflammation

xlomafota13 shared this article with you from Inoreader Tolerogenic dendritic cells suppress titanium particle-induced inflammation Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):712. doi: 10.3892/etm.2021.10144. Epub 2021 May 3. ABSTRACT Aseptic loosening is a major complication of prosthetic joint surgery. The leading cause of arthroplasty failure is particulate wear debris such as titanium particles. Dendritic cells (DCs) are one type of immune cells that play an important role in the initiation and progression of inflammatory processes. DCs can develop into tolerogenic DCs (tolDCs), which present an alternative therapeutic strategy for inflammatory disorders. Previously, antigen-specific tolDCs were generated, which showed a promising effect in treating inflammatory arthritis and immune thrombocytopenia. The present study reports that tolDCs effectively inhibited titanium particle-induced inflammation in an air-pouch mouse model by decreasing pro-inflammatory cytokines. In addition, a mechanistic study demonstrated that tolDCs significantly protected against titanium particle-in duced inflammatory processes in vitro by releasing anti-inflammatory cytokines, such as interleukin-10. Collectively, these findings not only demonstrate that tolDCs play an important role in inhibiting titanium particle-induced inflammation but also provide a potential alternative for the prevention or treatment of titanium particle-induced inflammation. PMID:34007321 | PMC:PMC8120651 | DOI:10.3892/etm.2021.10144 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

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.