Naringin attenuates rat myocardial ischemia/reperfusion injury via PI3K/Akt pathway-mediated inhibition of apoptosis, oxidative stress and autophagy

xlomafota13 shared this article with you from Inoreader Naringin attenuates rat myocardial ischemia/reperfusion injury via PI3K/Akt pathway-mediated inhibition of apoptosis, oxidative stress and autophagy Via Experimental and therapeutic medicine Exp Ther Med. 2021 Aug;22(2):811. doi: 10.3892/etm.2021.10243. Epub 2021 May 28. ABSTRACT Naringin (NRG) has been reported to exert cardioprotective effects against multiple cardiovascular diseases, including lipopolysaccharide-induced and hyperglycemia-induced myocardial injury. However, the role of NRG in myocardial ischemia/reperfusion (I/R) injury remains unclear. In the present study, the PI3K/Akt pathway was investigated to evaluate the possible mechanisms underlying the roles of NRG in myocardial ischemia/reperfusion (I/R) injury. The levels of cardiac enzymes were measured by ELISA to evaluate the optimal dosage of NRG that could protect against myocardial I/R injury. Rats were administered 100 mg/kg of NRG and activities of myocardial enzymes, the level of cardiac apoptosis and inflammation, oxidant response, autophagy indicators and echocardiography were evaluated. The level of corresponding proteins was measured using wester n blotting. The results indicated that NRG elicited the best cardioprotective effects at a dose of 100 mg/kg by significantly reducing the levels of myocardial enzymes, apoptosis, inflammation, oxidative response and infarct size. Furthermore, NRG alleviated contractile dysfunction by increasing the left ventricular ejection fraction and fractional shortening. In addition, NRG markedly promoted the phosphorylation of Akt, while decreasing the level of autophagy indicator beclin-1 and the microtubule-associated protein 1B-light chain 3 (LC3B) II/ LC3BI ratio. However, PI3K/Akt inhibitor (LY294002) partially reduced the NRG induced phosphorylation of Akt and the reduction in beclin-1, along with the LC3BII/LC3BI ratio. The results of the present study demonstrated that NRG could attenuate myocardial I/R injury. PMID:34131434 | PMC:PMC8193209 | DOI:10.3892/etm.2021.10243 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

miR-452-5p regulates the responsiveness of intestinal epithelial cells in inflammatory bowel disease through Mcl-1

xlomafota13 shared this article with you from Inoreader miR-452-5p regulates the responsiveness of intestinal epithelial cells in inflammatory bowel disease through Mcl-1 Via Experimental and therapeutic medicine Exp Ther Med. 2021 Aug;22(2):813. doi: 10.3892/etm.2021.10245. Epub 2021 May 28. ABSTRACT Inflammatory bowel diseases (IBDs) are chronic immune disorders that occur in the intestinal tract. Previous studies have revealed that intestinal epithelial cells (IECs) play critical roles in the development of IBDs, and therapies targeting IECs hold great potential for the treatment of IBDs. However, the roles of microRNAs (miRs) in the regulation of IEC properties and whether they can be used as targets for IEC regulation and IBD treatment are largely unknown. The aim of the present study was to investigate the role of the miR-452-5p/Mcl-1 axis in the regulation of the properties of IECs during the pathology of IBD. A dextran sulfate sodium-induced mouse model of ulcerative colitis (UC) and an in vitro lipopolysaccharide-stimulated IEC-6 cell model were investigated. The results revealed that miR-452-5p expression in the IECs of the mic e increased significantly upon UC induction, and the knockdown of miR-452-5p alleviated the IBD symptoms. Furthermore, the suppression of miR-452-5p downregulated the expression of the inflammatory cytokines IL-6, IL-8 and TNFα, and upregulated the expression of intestinal barrier-associated molecules, namely occludin, zona occludens 1 and mucin-2 in IECs in vitro and in vivo. Notably, the results indicated that miR-452-5p modulated the responses of IECs by negatively regulating the expression of Mcl-1, as the knockdown of Mcl-1 abrogated the effects of miR-452-5p suppression on IECs. The present study suggested that miR-452-5p regulated the responsiveness of IECs to influence the development of UC in an Mcl-1-dependent manner. These observations provide important information to improve the understanding of IBD pathogenesis and indicate that targeting the miR-452-5p-Mcl-1 signaling axis in IECs holds potential for IBD treatment. PMID:34131436 | PMC:PMC8193216 | DOI:10.3892/etm.2021.10245 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Zwint facilitates melanoma progression by promoting c-Myc expression

xlomafota13 shared this article with you from Inoreader Zwint facilitates melanoma progression by promoting c-Myc expression Via Experimental and therapeutic medicine Exp Ther Med. 2021 Aug;22(2):818. doi: 10.3892/etm.2021.10250. Epub 2021 Jun 2. ABSTRACT ZW10 interactor (Zwint) is upregulated in various types of tumors and exerts a carcinogenic effect. However, little is known about the expression profile, function and molecular mechanisms of action of Zwint in melanoma. Therefore, the aim of the present study was to investigate the expression levels of Zwint in melanoma cell lines and tissues. It was revealed that Zwint was highly expressed in melanoma samples. Functional experiments indicated that Zwint knockdown suppressed the proliferation and migration of A375 melanoma cells. Further mechanistic studies demonstrated that Zwint knockdown decreased the protein expression levels of c-Myc, MMP-2, Slug, mTOR, phosphorylated (p)-mTOR, p-p38 and fibronectin, while it increased the protein expression levels of E-cadherin and MMP-9. Among these genes, c-Myc, MMP-2 and Slug were overexpressed to investi gate their effects on cell proliferation following Zwint knockdown. The results demonstrated that overexpression of c-Myc, but not MMP-2 or Slug, rescued the effects of Zwint knockdown on melanoma cell proliferation and migration. Taken together, the results of the present study suggested that Zwint may act as an oncogene in melanoma by regulating c-Myc expression. PMID:34131441 | PMC:PMC8193213 | DOI:10.3892/etm.2021.10250 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Effect of C reactive protein on the sodium-calcium exchanger 1 in cardiomyocytes

xlomafota13 shared this article with you from Inoreader Effect of C reactive protein on the sodium-calcium exchanger 1 in cardiomyocytes Via Experimental and therapeutic medicine Exp Ther Med. 2021 Aug;22(2):815. doi: 10.3892/etm.2021.10247. Epub 2021 May 28. ABSTRACT Numerous previous studies have found that C-reactive protein (CRP) is associated with cardiac arrhythmia and cardiac remodeling. However, the underlying mechanisms of this association remain unclear. Sodium-calcium exchanger 1 (NCX1) serves an important role in the regulation of intracellular calcium concentration, which is closely related with cardiac arrhythmia and cardiac remodeling. The present study aimed to evaluate the effects of CRP on NCX1 and intracellular calcium concentration in cardiomyocytes. Primary neonatal mouse ventricular cardiomyocytes were cultured and treated with varying concentrations of CRP (0, 5, 10, 20 and 40 µg/ml). The cardiomyocytes were also treated with NF-κB-specific inhibitor PTDC and a specific inhibitor of the reverse NCX1 KB-R7943 before their intracellular calcium concentrations were measured. mRNA and prote in expression levels of NCX1 were detected by reverse transcription-quantitative PCR and western blotting, respectively and intracellular calcium concentration was evaluated by flow cytometry. CRP treatment significantly increased mRNA and protein expression levels of NCX1 in myocytes (P=0.024), as well as intracellular calcium concentration (P=0.01). These results were significantly attenuated by the NF-κB-specific inhibitor PDTC and a specific inhibitor of the reverse NCX1, KB-R7943. CRP significantly upregulated NCX1 expression and increased intracellular calcium concentration in cardiomyocytes via the NF-κB pathway, suggesting that CRP may serve a pro-arrhythmia role via direct influence on the calcium homeostasis of cardiomyocytes. PMID:34131438 | PMC:PMC8193207 | DOI:10.3892/etm.2021.10247 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Efficacy of simvastatin on carotid atherosclerotic plaque and its effects on serum inflammatory factors and cardiocerebrovascular events in elderly patients

xlomafota13 shared this article with you from Inoreader Efficacy of simvastatin on carotid atherosclerotic plaque and its effects on serum inflammatory factors and cardiocerebrovascular events in elderly patients Via Experimental and therapeutic medicine Exp Ther Med. 2021 Aug;22(2):819. doi: 10.3892/etm.2021.10251. Epub 2021 Jun 2. ABSTRACT To investigate the efficacy of simvastatin on carotid atherosclerotic plaque (CAP) and its effects on serum inflammatory factors and cardiocerebrovascular events in elderly patients, 130 elderly patients with CAP were randomly divided into observation (n=65) and control groups (n=65). The control group was treated with 75 mg/day aspirin enteric-coated tablets, and the observation group was administered additional 20 mg/day simvastatin. Serum total cholesterol, triglyceride, and high- and low-density lipoprotein cholesterol levels (evaluated via the endpoint method) were determined in both groups. Furthermore, the length, thickness and number of CAPs was measured using color Doppler ultrasonography. In addition, levels of inflammatory biomarkers including high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), nitric oxide, D-dimer and fibrinogen, as well as change in microemboli count, were also compared After treatment, the observation group exhibited a significant reduction in size, thickness, and number of CAP and intima-media thickness compared with before treatment. However, no significant difference was found in the indicators of CAPs in the control group before and after treatment. The levels of total cholesterol, triglyceride, and low-density lipid cholesterol decreased, while high-density lipid cholesterol increased in the observation group after treatment, with notable changes in the observation group compared with in the control group. Overall response rate was higher in the observation group compared with the control group. TNF-α, IL-6, and hs-CRP levels in the observation group decreased after treatment compared with those before treatment and those in the control group. Furthermore, the rate of microemboli positivity was lower in the observation group than in the c ontrol group. Moreover, the overall incidence of acute cardiocerebrovascular events was lower in the observation group than in the control group. Therefore, it was demonstrated that simvastatin can reduce blood lipid levels, decrease the quantity and size of plaques, alleviate inflammatory response, reduce microemboli formation and reduce the risk of cardiocerebrovascular events in elderly patients with CAP. PMID:34131442 | PMC:PMC8193215 | DOI :10.3892/etm.2021.10251 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Effect of the ACY-1 gene on HER2 and TRAIL expression in rectal carcinoma

xlomafota13 shared this article with you from Inoreader Effect of the ACY-1 gene on HER2 and TRAIL expression in rectal carcinoma Via Experimental and therapeutic medicine Exp Ther Med. 2021 Aug;22(2):817. doi: 10.3892/etm.2021.10249. Epub 2021 Jun 2. ABSTRACT The incidence of rectal carcinoma (RC) is increasing and the age at onset of the disease is reducing. Therefore, elucidating the pathogenesis of RC is beneficial for early diagnosis and improving the prognosis. Aminoacylase-1 (ACY-1) is abnormally expressed in various malignant tumor tissues. Furthermore, the human epidermal growth factor receptor-2 (HER2) gene is involved in tumor metastasis and invasion, while tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces tumor cell apoptosis. The aim of the present study was to investigate the effect of the ACY-1 gene on the expression of HER2 and TRAIL in RC. Cancerous and adjacent tissues from RC patients were collected. ACY-1 expression was analyzed by immunohistochemistry. The rectal cancer cell lines HT29 and SW620, and normal colorectal mucosal epithelial fetal human cells were cu ltured in vitro. ACY-1 gene and protein expression levels were tested by reverse transcription-quantitative PCR and western blotting. ACY-1 small interfering RNA (siRNA) was transfected into HT29 and SW620 cells. Cell proliferation was detected by thiazolyl blue MTT assay. Caspase-3 activity was assessed using a commercial kit. HER2 and TRAIL expression levels were determined by western blotting. ACY-1 expression was significantly increased in cancer tissue compared with adjacent tissue (P<0.05). ACY-1 expression was elevated in HT29 and SW620 cells compared with normal colorectal mucosal epithelial cells (P<0.05). ACY-1 siRNA transfected into HT29 cells downregulated its expression, inhibited cell proliferation, enhanced caspase-3 activity, reduced HER2 expression and upregulated TRAIL expression (P<0.05). ACY-1 expression was found to be increased in rectal cancer tissue. Therefore, targeting the ACY-1 gene may regulate HER2 and TRAIL expression levels, and may red uce the occurrence and inhibit the development of rectal cancer. PMID:34131440 | PMC:PMC8193208 | DOI:10.3892/etm.2021.10249 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Significant effects of Ganoderma lucidum polysaccharide on lipid metabolism in diabetes may be associated with the activation of the FAM3C-HSF1-CAM signaling pathway

xlomafota13 shared this article with you from Inoreader Significant effects of <em>Ganoderma lucidum</em> polysaccharide on lipid metabolism in diabetes may be associated with the activation of the FAM3C-HSF1-CAM signaling pathway Via Experimental and therapeutic medicine Exp Ther Med. 2021 Aug;22(2):820. doi: 10.3892/etm.2021.10252. Epub 2021 Jun 2. ABSTRACT Diabetes is a threat to patient health worldwide. Type 2 diabetes (T2DM), one of the two main types of diabetes, is a long-term metabolic disease caused by heredity and environmental factors. It has been reported that Ganoderma lucidum polysaccharide (GLP) significantly decreased the concentration of blood glucose, promoted insulin secretion, improved glucose tolerance and regulated the concentration of blood lipids. In the present study, a T2DM model was established in db/db mice, following which T2DM mice were treated with GLP (100 and 400 mg/kg) for 8 weeks, with MET used as the positive control. The glycosylated hemoglobin (HbAlc) and fasting blood glucose (FBG) levels, and diabetes-associated clinical chemistry indexes were detected in the blood and serum of each mouse. Hematoxylin and eosin, and oil red O staining were performed on the livers of each mouse to evaluate the level of liver fat. The expression levels of family with sequence similarity 3 (FAM3C), heat shock factor 1 (HSF1), calmodulin (CaM), AKT and phosphorylated (p)-AKT were detected in the hepatocytes of T2DM mice using reverse transcription-quantitative PCR and western blotting. The results demonstrated that the unbalanced levels of HbAlc, FBG and diabetes-related index in T2DM mice were significantly improved by treatment with GLP. Lipid droplets in the hepatocytes of mice shrank in the GLP groups compared with the model control group. The expression levels of FAM3C, HSF1, CaM and p-AKT/AKT in the hepatocytes of T2DM mice were significantly increased following treatment with GLP. In conclusion, GLP exerted significant effects on lipid metabolism in diabetes, which may be associated with the activation of the FAM3C-HSF1-CaM signaling pathway. PMID:34131443 | PMC:PMC8193219 | DOI:10.3892/etm.2021.10252 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Activation of the NLRC4 inflammasome in renal tubular epithelial cell injury in diabetic nephropathy

xlomafota13 shared this article with you from Inoreader Activation of the NLRC4 inflammasome in renal tubular epithelial cell injury in diabetic nephropathy Via Experimental and therapeutic medicine Exp Ther Med. 2021 Aug;22(2):814. doi: 10.3892/etm.2021.10246. Epub 2021 May 28. ABSTRACT Renal tubular interstitial injury plays a key role in the progression of diabetic nephropathy (DN) and, thus, the study of renal tubular injury in DN is important. The aim of the present study was to elucidate the role of the NLR family CARD domain containing 4 (NLRC4) inflammasome in renal tubular epithelial cell (RTEC) injury in DN. Human kidney biopsy tissues were obtained from patients with DN, and normal kidney tissues were obtained from nephrectomies performed for renal hamartoma. Human RTECs (HK2 cells) were divided into normal glucose (D-glucose 5.6 mmol/l), high glucose (HG; 30 mmol/l), high osmotic (D-glucose 5.6 mmol/l + D-mannitol 24.4 mmol/l), HG + NLRC4 small interfering (si)RNA or HG + siRNA control groups. Then, the expression levels of NLRC4, PTEN-induced kinase 1 (PINK1) and parkin, as well as the levels of mitochondrial reactive oxygen species, which are associated with mitophagy, were observed. The expression levels of NLRC4, PINK1, parkin and phosphorylated parkin in the RTECs of patients with DN were higher compared with those in normal controls. In HK2 cells, HG stimulated the expression of NLRC4, the secretion of IL-1β and IL-18 and cell death. Moreover, knockdown of NLRC4 expression in HK2 cells treated with HG reduced the secretion of the inflammatory cytokines, IL-1β and IL-18. The findings of the present study may provide a rationale for the development of treatments for patients with DN by preventing inflammasome activation. PMID:34131437 | PMC:PMC8193214 | DOI:10.3892/etm.2021.10246 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Identification of key candidate genes in local dorsal root ganglion inflammation by integrated bioinformatics analysis

xlomafota13 shared this article with you from Inoreader Identification of key candidate genes in local dorsal root ganglion inflammation by integrated bioinformatics analysis Via Experimental and therapeutic medicine Exp Ther Med. 2021 Aug;22(2):821. doi: 10.3892/etm.2021.10253. Epub 2021 Jun 2. ABSTRACT The purpose of the present study was to identify potential markers of local dorsal root ganglion (DRG) inflammation to aid diagnosis, treatment and prognosis evaluation of DRG pain. A localized inflammation of the DRG (LID) rat model was used to study the contribution of inflammation to pain. The dataset GSE38859 was obtained from the Gene Expression Omnibus database. Pre-treatment standardization of gene expression data for each experiment was performed using the R/Bioconductor Limma package. Differentially expressed genes (DEGs) were identified between a LID model and a sham surgery control group. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of DEGs and gene set enrichment analysis (GSEA) were carried out using the 'clusterProfiler' package in R. Using the Search Tool for Retrieval of Interacting Genes, a protein-protein interaction network was constructed and visualized. Candidate genes with the highest potential validity were validated using reverse transcription-quantitative PCR and western blotting. In total, 66 DEGs were enriched in GO terms related to inflammation and the immune response processes. KEGG analysis revealed 14 associated signaling pathway terms. Protein-protein interaction network analysis revealed 9 node genes, 3 of which were among the top 10 DEGs. Matrix metallopeptidase 9, chemokine CXCL9, and complement component 3 were identified as key regulators of DRG inflammatory pain progression. PMID:34131444 | PMC:PMC8193217 | DOI:10.3892/etm.2021.10253 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

REM sleep behaviour disorder in Parkinson's disease (Review)

xlomafota13 shared this article with you from Inoreader REM sleep behaviour disorder in Parkinson's disease (Review) Via Experimental and therapeutic medicine Exp Ther Med. 2021 Aug;22(2):812. doi: 10.3892/etm.2021.10244. Epub 2021 May 28. ABSTRACT Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia defined by simple or complex abnormal movements occurring in REM state, instead of the physiological muscular atonia. RBD may be idiopathic, or secondary as in the case of Parkinson's disease (PD). Several studies have confirmed that idiopathic RBD may precede with several years the onset of the specific motor characteristics of PD. The high prevalence of RBD in PD (19-70%) may be explained by several common pathophysiological pathways, mainly related to the dopaminergic cell loss. RBD is also associated with several comorbidities, including cognitive impairment, hallucinations, dysautonomia, or daytime sleepiness. The gold standard investigation for the diagnosis and assessment of RBD is video polysomnography, but in clinical practice, the use of clinical scales and questionna ires is reasonable for the screening of this complex parasomnia. Management options include ensuring a safe environment for the patient and pharmacological treatment, incuding clonazepam, melatonin or certain antiparkinsonian drugs. PMID:34131435 | PMC:PMC8193212 | DOI:10.3892/etm.2021.10244 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.