Modulation of the ERK1/2-MMP-2 pathway in the sclera of guinea pigs following induction of myopia by flickering light

xlomafota13 shared this article with you from Inoreader Modulation of the ERK1/2-MMP-2 pathway in the sclera of guinea pigs following induction of myopia by flickering light Via Experimental and therapeutic medicine Exp Ther Med. 2021 Apr;21(4):371. doi: 10.3892/etm.2021.9802. Epub 2021 Feb 19. ABSTRACT It has been shown that flickering light can affect the development of eyeballs. However, the exact mechanism remains unclear. The ERK1/2-MMP-2 pathway is a classic pathway involved in the modulation of the extracellular matrix (ECM) in cancer tissues. However, to the best of our knowledge, the role of this pathway in modulating the scleral ECM in myopia has not been previously examined. The present study aimed to determine the effects of the ERK1/2-MMP-2 pathway on the formation of flickering light-induced myopia (FLM). Guinea pigs were raised under illumination at a flash rate of 0.5 Hz for 6 weeks to induce FLM. Peribulbar injections of dimethylsulfoxide or PD98059 (an inhibitor of phospho-ERK1/2) were administered starting at the third week of FLM modeling. Refraction was measured prior to and following treatments. The thickness of the posterior sclera (PS) was measured under a light microscope following H&E staining. The mRNA levels of MMP-2 were detected by the reverse transcription-quantitative PCR assay. The expression levels of MMP-2 and ERK1/2 were assayed by western blot and immunohistochemical analyses. Following 6 weeks of treatment, the refraction of the FLM group became more myopic compared with that of the control group, while PD98059 treatment inhibited the changes noted in the refraction. A marked reduction in the thickness of PS was observed in the FLM group, while PD98059 inhibited the remodeling of PS. In addition, the expression levels of MMP-2 and protein levels of phospho-ERK1/2 were increased in the FLM group, while PD98059 significantly inhibited MMP-2 mRNA and protein levels. These results indicated that ERK1/2-MMP-2 may be involved in the formation of FLM in guinea pigs by regulating the remodeling of PS. PMID:33732344 | PMC:PMC7903414 | DOI:10.3892/etm.2021.9802 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Effects of neutron radiation on Nrf2-regulated antioxidant defense systems in rat lens

xlomafota13 shared this article with you from Inoreader Effects of neutron radiation on Nrf2-regulated antioxidant defense systems in rat lens Via Experimental and therapeutic medicine Exp Ther Med. 2021 Apr;21(4):334. doi: 10.3892/etm.2021.9765. Epub 2021 Feb 8. ABSTRACT Accumulating evidence suggests that ionizing radiation (IR)-induced cataract may be associated with oxidative stress. Nuclear factor erythroid 2-related factor 2 (Nrf2) serves as a master regulator of the antioxidant defense system against oxidative stress. The present study aimed to investigate the effects of different doses of neutron radiation on the Nrf2-reegulated antioxidant defense system in rat lens and assess the status of oxidative stress. A total of 24 SD rats were randomly divided into the following four groups: i) Control group; iis) 0.4 Sv group; iii) 1.2 Sv group; and iv) 3.6 Sv group. The rats were sacrificed 7 days after radiation and lenses were dissected for histological, biochemical (malondialdehyde, glutathione and superoxide dismutase) and western blot (Nrf2, glutamate-cysteine ligase catalytic subunit and heme oxygenase 1) ana lyses. The morphological features of the lenses remained intact in the 0.4 Sv, 1.2 Sv and control groups, whilst the lenses in the 3.6 Sv group exhibited injuries. Results from the TUNEL assay demonstrated apparent apoptosis in lens epithelial cells following 3.6 Sv neutron radiation whereas sparse apoptosis was observed following 0.4 Sv and 1.2 Sv radiation. Malondialdehyde levels were reduced in the 0.4 Sv and 1.2 Sv groups but increased in the 3.6 Sv group, compared with those in the control group. Conversely, glutathione expression and the activity of superoxide dismutase were higher in the 0.4 Sv and 1.2 Sv groups, but lower in the 3.6 Sv group, compared with those in the control group. In addition, the total and nuclear protein levels of Nrf2 were increased following neutron radiation compared with those in the control group, though the Nrf2 protein levels decreased in the 3.6 Sv group compared with those in the 1.2 Sv group. The levels of glutamate-cysteine ligase catalytic s ubunit and heme oxygenase 1, downstream antioxidant enzymes of Nrf2, demonstrated the same profile as that in Nrf2. Taken together, the results of the present study suggest that neutron radiation affects Nrf2-regulated antioxidant systems in a two-stage process. Namely, the induction phase for low-dose radiation and regression phase for high-dose radiation. Therefore, it was hypothesized that activation and enhancement of the Nrf2-regulated antioxidant system may be useful in preventing or delaying IR-induced cataract, which may be extended even for other diseases associated with oxidative stress. PMID:33732307 | PMC:PMC7903385 | DOI:10.3892/etm.2021.9765 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Downregulation of DEC1 inhibits proliferation, migration and invasion, and induces apoptosis in ovarian cancer cells via regulation of Wnt/β-catenin signaling pathway

xlomafota13 shared this article with you from Inoreader Downregulation of DEC1 inhibits proliferation, migration and invasion, and induces apoptosis in ovarian cancer cells via regulation of Wnt/β-catenin signaling pathway Via Experimental and therapeutic medicine Exp Ther Med. 2021 Apr;21(4):372. doi: 10.3892/etm.2021.9803. Epub 2021 Feb 19. ABSTRACT DEC1 has been reported to regulate the expression of multiple target genes, participate in cell differentiation, apoptosis, aging and the development and progression of numerous tumors, but the detailed effects and possible mechanisms of DEC1 in ovarian cancer (OC) remain unknown. The present study aimed to investigate the expression and mechanism of function of DEC1 in OC. The present results demonstrated that DEC1 was highly expressed in OC tissues and cell lines using reverse transcription-quantitative PCR, western blotting and immunohistochemistry, and high expression of DEC1 was negatively associated with the prognosis of patients with OC. In addition, knockdown of DEC1 significantly inhibited proliferation in SKOV3 and OVCAR3 cells compared with control. DEC1 knockdown also induced apoptosis and increased the expression of apoptosis-related p roteins in OC cells. The results suggested that knockdown of DEC1 inhibited OC cell migration and invasion via regulation of epithelial-mesenchymal transition-related protein. It was also found that DEC1 knockdown significantly inhibited the Wnt/β-catenin pathway. Collectively, the current results indicated that knockdown of DEC1 inhibited proliferation, migration and invasion, and induced apoptosis in OC cells via modulating the Wnt/β-catenin signaling pathway. Thus, DEC1 may participate in malignant progression of OC, and may be a target for treatment and diagnosis of OC. PMID:33732345 | PMC:PMC7903451 | DOI:10.3892/etm.2021.9803 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Ckip-1 regulates C3H10T1/2 mesenchymal cell proliferation and osteogenic differentiation via Lrp5

xlomafota13 shared this article with you from Inoreader Ckip-1 regulates C3H10T1/2 mesenchymal cell proliferation and osteogenic differentiation via Lrp5 Via Experimental and therapeutic medicine Exp Ther Med. 2021 Apr;21(4):342. doi: 10.3892/etm.2021.9773. Epub 2021 Feb 10. ABSTRACT Casein kinase-2 interaction protein-1 (Ckip-1) is a negative regulator of bone formation. The identification of novel Ckip-1-related targets and their associated signaling pathways that regulate mesenchymal stem cell (MSC) osteogenic differentiation is required. The present study aimed to evaluate the effects of Ckip-1 knockdown on C3H10T1/2 MSC proliferation and osteogenic differentiation, and to explore the role of the canonical Wnt-signaling receptor Lrp5. Ckip-1-knockdown (shCkip-1), Ckip-1-overexpression (Ckip-1) and their corresponding control [shCtrl and empty vector (EV), respectively] cell groups were used in the present study. Immunofluorescence localization of Ckip-1 was observed. The expression of the key molecules of the canonical Wnt signaling pathway was examined in C3H10T1/2 cells following osteogenic induction. Moreover, the effect s of Lrp5 knockdown in the presence or absence of Ckip-1 knockdown were examined on C3H10T1/2 cell proliferation and osteogenic differentiation. The results indicated an increase in cell proliferation and osteogenic differentiation in the shCkip-1 group compared with the shCtrl group. The expression levels of LDL receptor related protein 5 (Lrp5), lymphoid enhancer binding factor 1 (Lef1) and transcription factor 1 in C3H10T1/2 cells were significantly increased in shCkip-1 cells following 7-day osteoinduction compared with shCtrl cells. Moreover, the involvement of Lrp5 in shCkip-1-induced osteogenic differentiation of C3H10T1/2 cells was further verified. The results indicated that Ckip-1 reduced C3H10T1/2 MSC proliferation and osteogenic differentiation via the canonical Wnt-signaling receptor Lrp5, which is essential for the improvement of bone tissue engineering. PMID:33732315 | PMC:PMC7903475 | DOI:10.3892/etm.2021.9773 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

MicroRNA-145-5p aggravates cell apoptosis and oxidative stress in tongue squamous cell carcinoma

xlomafota13 shared this article with you from Inoreader MicroRNA-145-5p aggravates cell apoptosis and oxidative stress in tongue squamous cell carcinoma Via Experimental and therapeutic medicine Exp Ther Med. 2021 Apr;21(4):373. doi: 10.3892/etm.2021.9804. Epub 2021 Feb 19. ABSTRACT MicroRNA-145-5p (miR-145-5p) is expressed in a variety of tumors, but the mechanism underlying miR-145-5p in tongue squamous cell carcinoma (TSCC) is not fully understood. Therefore, the present study investigated the role of miR-145-5p in TSCC. miR-145-5p expression levels in TSCC tissues were analyzed via reverse transcription-quantitative PCR. miR-145-5p mimics and inhibitors were transfected into SCC9 and Cal27 cells. The stability and invasion of SCC9 and Cal27 cells were analyzed by performing Transwell assays, while PI and Annexin V were used to detect cell apoptosis. Oxidative stress levels of superoxide dismutase, malondialdehyde and glutathione peroxidase were measured via ELISA. PI3K/AKT signaling pathway-associated protein expression levels were evaluated using western blotting. miR-145-5p was consistently downregulated in TSCC tissues compared with healthy tissues. miR-145-5p overexpression decreased cell stability and invasion, but promoted cell apoptosis and oxidative stress. In addition, PI3K, AKT and phosphorylated-AKT expression levels were significantly diminished. The results indicated that miR-145-5p overexpression inhibited SCC9 and Cal27 cell stability and invasion, promoted SCC9 and Cal27 cell apoptosis and oxidative stress, and inhibited the PI3K/AKT signaling pathway. The results of the present study suggested that miR-145 may serve as a molecular marker of TSCC. PMID:33732346 | PMC:PMC7903421 | DOI:10.3892/etm.2021.9804 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Downregulation of miR-1184 serves as a diagnostic biomarker in neonatal sepsis and regulates LPS-induced inflammatory response by inhibiting IL-16 in monocytes

xlomafota13 shared this article with you from Inoreader Downregulation of miR-1184 serves as a diagnostic biomarker in neonatal sepsis and regulates LPS-induced inflammatory response by inhibiting IL-16 in monocytes Via Experimental and therapeutic medicine Exp Ther Med. 2021 Apr;21(4):350. doi: 10.3892/etm.2021.9781. Epub 2021 Feb 11. ABSTRACT Neonatal sepsis (NS) remains a global problem. In the present study, abnormal expression of microRNA-1184 (miR-1184) was detected in neonates with NS and it was endeavored to investigate the diagnostic value of miR-1184, as well as its regulatory role in lipopolysaccharide (LPS)-induced inflammatory response in vitro. Furthermore, the correlation between interleukin-16 (IL-16) and miR-1184 was investigated to elucidate the pathological mechanisms of NS development. Reverse transcription-quantitative PCR was used to detect the expression of miR-1184. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic value of miR-1184 in NS. Furthermore, a sepsis cell model was established by using LPS-induced monocytes to explore the effect of miR-1184 on the inflammatory response. The levels of inflammatory cytokines w ere determined by ELISA. A luciferase reporter assay was used to investigate the direct targeting interaction between miR-1184 and IL-16. The results indicated that the serum levels of miR-1184 in neonates with sepsis were decreased and miR-1184 had a high diagnostic value when differentiating NS from respiratory conditions in neonates. In vitro, the expression of miR-1184 in monocytes was inhibited by LPS and overexpression of miR-1184 reversed the effect of LPS to stimulate the inflammatory response. IL-16 was demonstrated to be a target of miR-1184 and a negative correlation between them was identified in patients with NS. The inflammatory response inhibited by miR-1184 mimics was enhanced by overexpression of IL-16 in LPS-induced monocytes. In conclusion, decreased levels of serum miR-1184 may be a potential diagnostic biomarker for NS. In addition, miR-1184 inhibited the LPS-induced inflammatory response by targeting IL-16 in monocytes, suggesting that the miR-1184/IL-16 axis may be a potential therapeutic target for NS. PMID:33732323 | PMC:PMC7903473 | DOI:10.3892/etm.2021.9781 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Piperine protects against myocardial ischemia/reperfusion injury by activating the PI3K/AKT signaling pathway

xlomafota13 shared this article with you from Inoreader Piperine protects against myocardial ischemia/reperfusion injury by activating the PI3K/AKT signaling pathway Via Experimental and therapeutic medicine Exp Ther Med. 2021 Apr;21(4):374. doi: 10.3892/etm.2021.9805. Epub 2021 Feb 19. ABSTRACT Piperine (PIP) exerts numerous pharmacological effects and its involvement in endoplasmic reticulum (ER) stress (ERS)-led apoptosis has garnered attention. The present study focused on whether PIP played protective effects on hypoxia/reoxygenation (H/R)-induced cardiomyocytes by repressing ERS-led apoptosis. The potential molecular mechanisms in association with the PI3K/AKT signaling pathway were investigated. Primary neonatal rat cardiomyocytes (NRCMs) were isolated and randomized into four groups: Control + vehicle group, control + PIP group, H/R + vehicle group and H/R + PIP group. The H/R injury model was constructed by 4 h of hypoxia induction followed by 6 h of reoxygenation. A total of 10 µM PI3K/AKT inhibitor LY294002 was supplemented to the cells during the experiments. Cell viability and myocardial enzymes were detected to evaluate myoc ardial damage. A flow cytometry assay was performed to assess apoptotic response. Western blot analysis was performed to detect the expression of related proteins including PI3K, AKT, CHOP, GRP78 and cleaved caspase-12. The results showed that H/R markedly promoted myocardial damage as shown by the increased release of lactate dehydrogenase and creatine kinase levels, but a reduction in cell viability. In addition, ERS-induced apoptosis was markedly promoted by H/R in NRCMs, as shown by the increased apoptotic rates and expression of C/EBP-homologous protein, endoplasmic reticulum chaperone BiP and caspase-12. PIP administration reversed cell injury and ERS-induced apoptosis in H/R. Mechanistic studies concluded that the apoptosis-inhibitory contributions and cardio-favorable effects of PIP were caused partly by the activation of the PI3K/AKT signaling pathway, which was verified by LY294002 administration. To conclude, PIP can reduce ERS-induced apoptosis by activating the PI3K/AKT signaling pathway during the process of H/R injury, which could be a potential therapeutic target for the treatment of myocardial ischemia/reperfusion injury. PMID:33732347 | PMC:PMC7903478 | DOI:10.3892/etm.2021.9805 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Anti-demodectic effects of okra eyelid patch in Demodex blepharitis compared with tea tree oil

xlomafota13 shared this article with you from Inoreader Anti-demodectic effects of okra eyelid patch in <em>Demodex</em> blepharitis compared with tea tree oil Via Experimental and therapeutic medicine Exp Ther Med. 2021 Apr;21(4):338. doi: 10.3892/etm.2021.9769. Epub 2021 Feb 10. ABSTRACT Demodex infection gradually develops to Demodex blepharitis, which is characterized as chronic inflammation of the eyelid and meibomian gland (MG) and ultimately leads to MG dysfunction. In the present prospective study, the anti-demodectic effects of an okra eyelid patch in patients Demodex blepharitis were investigated. A total of 52 patients with Demodex blepharitis with ocular discomfort were recruited. Patients were randomized to receive either an okra eyelid patch treatment (treatment group, n=27) or tea tree oil (TTO) eye care patch treatment (control group, n=25) for three months. The Demodex count, the ocular surface disease index (OSDI) score, MG expressibility (MGE) and meibum quality, Schirmer I test (SIT), tear break-up time (TBUT) and corneal fluorescein staining (CFS) were determined prior to treatm ent and after 1 and 3 months of treatment. Changes in the parameters were compared between the treatment group and control group after 1 and 3 months of treatment. The average survival time in the okra group was 115.25±11.87 min, which was significantly lower compared with the average ST of 378.75±37.94 min in the blank group (P<0.01). After 3 months of okra eyelid patch treatment, the Demodex count was significantly reduced from 10.15±4.53 to 1.30±1.41 (P<0.01) and the OSDI score of the patients was reduced by 16.84±10.17 (P<0.01). There was no significant difference in the Demodex count (P=0.716) and OSDI (P=0.873) between the treatment and control groups. The rate of complete Demodex eradication in the treatment group (11/27, 40.74%) was slightly lower than that in the control group (12/25, 48%), but there was no significant difference between the two groups (χ2=0.277, P=0.598). Regarding the other ocular parameters, no significant d ifference was observed in the TBUT, meibum quality and MGE between the two groups (P<0.05). TTO group has a significantly improvement compared with Okra group in terms of SIT (P=0.035) and CFS (P=0.023). In conclusion, okra eyelid patch treatment is able to significantly eradicate ocular Demodex as well as markedly alleviate ocular symptoms. Due to causing less irritation than TTO, the okra eyelid patch may be more suitable for sensitive patients with Demodex blepharitis, such as the elderly and children. The study was registered as a clinical trial in the Chinese Clinical Trial Registry (ChiCTR) in November 2018 (registration no. ChiCTR-1,800,019,466). PMID:33732311 | PMC:PMC7903416 | DOI:10.3892/etm.2021.9769 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

A clinical study on the factors associated with nasopharyngeal carcinoma among the Chinese population

xlomafota13 shared this article with you from Inoreader A clinical study on the factors associated with nasopharyngeal carcinoma among the Chinese population Via Experimental and therapeutic medicine Exp Ther Med. 2021 Apr;21(4):375. doi: 10.3892/etm.2021.9806. Epub 2021 Feb 19. ABSTRACT Nasopharyngeal carcinoma (NC) arises from the nasopharynx epithelium and the majority of NC cases globally are within China and Southeast Asia. Both short palate lung and nasal epithelium clone 1 (SPLUNC1) and myelodysplasia syndrome 1-ectopic viral integration site 1 (MDS1-EVI1) play an important role in carcinogenesis and have been found to be associated with nasopharyngeal carcinoma. In spite of their role in NC, the association between these genes and their polymorphisms in the development of NC has thus far not been studied. In the present study, the relationship between SPLUNC1 (rs2752903, T>C) and MDS1-EVI1 (rs6774494, G>A) polymorphisms and their role in the development of NC among the Chinese population were investigated. From a Chinese population of 1,059 patients with NC and 891 controls, genotype frequencies and the distribution o f SPLUNC1 and MDS1-EVI1 polymorphisms were analyzed for possible susceptibility to NC. It was observed that those with MDS1-EVI1 CC (OR, 2.76; 95% CI, 1.96-3.81) and MDS1-EVI1 CT (OR, 1.51; 95% CI, 1.22-2.14) polymorphisms had an increased risk of developing NC. Those with SPLUNC1 AA genotypes also observed a higher risk for NC compared with SPLUNC1 GG genotypes (OR, 2.15; 95% CI, 1.62-3.15). When observing the gene-gene interaction between SPLUNC1 and MDS1-EVI1 polymorphisms, it was found that the presence of both SPLUNC1 CC and MDS1-EVI1 AA alleles was associated with a higher risk for NC compared with those who did not carry both alleles (OR, 6.75; 95% CI, 3.41-12.11). The present study suggested that the association between SPLUNC1 (rs2752903, T>C) and MDS1-EVI1 (rs6774494, G>A) polymorphisms may be a potent risk factor in the occurrence of NC. PMID:33732348 | PMC:PMC7903443 | DOI:10.3892/etm.2021.9806 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Screening and verification of hub genes involved in osteoarthritis using bioinformatics

xlomafota13 shared this article with you from Inoreader Screening and verification of hub genes involved in osteoarthritis using bioinformatics Via Experimental and therapeutic medicine Exp Ther Med. 2021 Apr;21(4):330. doi: 10.3892/etm.2021.9761. Epub 2021 Feb 8. ABSTRACT Osteoarthritis (OA) is one of the most common causes of disability and its development is associated with numerous factors. A major challenge in the treatment of OA is the lack of early diagnosis. In the present study, a bioinformatics method was employed to filter key genes that may be responsible for the pathogenesis of OA. From the Gene Expression Omnibus database, the datasets GSE55457, GSE12021 and GSE55325 were downloaded, which comprised 59 samples. Of these, 30 samples were from patients diagnosed with osteoarthritis and 29 were normal. Differentially expressed genes (DEGs) were obtained by downloading and analyzing the original data using bioinformatics. The Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathways were analyzed using the Database for Annotation, Visualization and Integrated Discovery online database. Pr otein-protein interaction network analysis was performed using the Search Tool for the Retrieval of Interacting Genes/proteins online database. BSCL2 lipid droplet biogenesis associated, seipin, FOS-like 2, activator protein-1 transcription factor subunit (FOSL2), cyclin-dependent kinase inhibitor 1A (CDKN1A) and kinectin 1 (KTN1) genes were identified as key genes by using Cytoscape software. Functional enrichment revealed that the DEGs were mainly accumulated in the ErbB, MAPK and PI3K-Akt pathways. Reverse transcription-quantitative PCR analysis confirmed a significant reduction in the expression levels of FOSL2, CDKN1A and KTN1 in OA samples. These genes have the potential to become novel diagnostic and therapeutic targets for OA. PMID:33732303 | PMC:PMC7903481 | DOI:10.3892/etm.2021.9761 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.