Distinct phenotypic expression levels of macrophages in neonatal lungs

xlomafota13 shared this article with you from Inoreader Distinct phenotypic expression levels of macrophages in neonatal lungs Via Experimental and therapeutic medicine Exp Ther Med. 2021 Apr;21(4):369. doi: 10.3892/etm.2021.9800. Epub 2021 Feb 19. ABSTRACT Alveolar macrophages are the front-line defense against environmental pathogens. However, to the best of our knowledge, differences in function and phenotypic expression levels of macrophages between neonatal and adult lungs have not previously been determined. The present study investigated lung tissues and analyzed blood samples to find cell markers of M1 and M2 macrophages in neonatal and adult rats. Pulmonary sepsis was induced by intrapleural instillation of lipopolysaccharide (LPS; 20 mg/kg) and survival time after administration of LPS was measured. In certain neonates, a selective inducible nitric oxide synthase (iNOS) inhibitor, 1400w, was administered prior to induction of pulmonary sepsis. Compared with adults, fetal and neonatal lung tissues had significantly higher levels of iNOS and CD86 (M1 markers), whereas the expression levels of CD206 and arginase-1 (M2 markers) were lower in the neonatal lung. The circulating cells that co-expressed CD68 (monocytes and macrophages) and CD86 in the blood were also significantly higher in neonates than in adults (25.9±6.6 vs. 11.6±2.2%; P=0.007. At basal unstimulated conditions, lung tissue concentrations of nitrite and nitrate (NOx) were significantly lower in the neonates than in adults (112.1±55.9 vs. 340.9±124.9 µM/g; P<0.001). However, NOx was increased following administration of LPS. Administration of 1400w suppressed lung tissue levels of NOx and improved the survival time in neonatal rats treated with LPS. The present study demonstrated that M1 is the primary macrophage phenotype in the neonatal lung and that higher iNOS expression levels do not have a protective effect against pulmonary endotoxins in neonates. Overproduction of NO by iNOS in neonatal alveolar macrophages may result in detrimental effects during pulmonary inflammation. PMID:33732342 | PMC:PMC7903444 | DOI:10.3892/etm.2021.9800 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Biomechanical evaluation of a customized 3D-printed polyetheretherketone condylar prosthesis

xlomafota13 shared this article with you from Inoreader Biomechanical evaluation of a customized 3D-printed polyetheretherketone condylar prosthesis Via Experimental and therapeutic medicine Exp Ther Med. 2021 Apr;21(4):348. doi: 10.3892/etm.2021.9779. Epub 2021 Feb 11. ABSTRACT The present study aimed to evaluate the biomechanical behavior of a custom 3D-printed polyetheretherketone (PEEK) condylar prosthesis using finite element analysis and mechanical testing. The Mimics software was used to create a 3D model of the mandible, which was then imported into Geomagic Studio software to perform osteotomy of the lesion area. A customized PEEK condyle prosthesis was then designed and the finite element model of the PEEK condyle prosthesis, mandible and fixation screw was established. The maximum stress of the prosthesis and screws, as well as stress and strain of the cortical and cancellous bones in the intercuspal position, incisal clench, left unilateral molar clench and right unilateral molar clench was analyzed. The biomechanical properties of the prosthesis were studied using two models with different lesion ranges. To si mulate the actual clinical situation, a special fixture was designed. The compression performance was tested at 1 mm/min for the condyle prosthesis, prepared by fused deposition modeling (FDM). The results of a finite element analysis suggested that the maximum stress of the condyle was 10.733 MPa and the maximum stress of the screw was 9.7075 MPa; both were far less than the yield strength of the material. The maximum force that the two designed prostheses were able to withstand was 3,814.7±442.6 N (Model A) and 4,245.7±348.3 N (Model B). Overall, the customized PEEK condyle prostheses prepared by FDM exhibited a uniform stress distribution and good mechanical properties, providing a theoretical basis for PEEK as a reconstruction material for repairing the temporomandibular joint. PMID:33732321 | PMC:PMC7903381 | DOI:10.3892/etm.2021.9779 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

18F-fluorodeoxyglucose positron emission tomography for the detection of inflammatory lesions of the arterial vessel walls in Wistar rats

xlomafota13 shared this article with you from Inoreader <sup>18</sup>F-fluorodeoxyglucose positron emission tomography for the detection of inflammatory lesions of the arterial vessel walls in Wistar rats Via Experimental and therapeutic medicine Exp Ther Med. 2021 Apr;21(4):370. doi: 10.3892/etm.2021.9801. Epub 2021 Feb 19. ABSTRACT The present study aimed to evaluate the use of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) for detection of high-fat and high-salt diet-induced inflammatory lesions of the arterial vessel walls in Wistar rats. A total of 20 healthy, 8-week-old, male Wistar rats were randomly assigned to the high-fat diet group and the normal diet group. After 16 and 24 weeks of feeding, Wistar rats in the normal diet group and the high-fat diet group (five rats in each group) were injected with 18F-FDG through the tail vein at a dose of 1 mCi/kg after fasting for 12 h. After 1 h, the rats were anesthetized with 2% isoflurane, followed by micro-PET imaging with a 10-min image capture duration and immunohistochemical staining. The standardized uptake values (SUVs) of 18F-FDG were significantly higher in the iliac artery in the high-fat diet group compared with those in the normal diet group at 16 weeks (1.53±0.08 vs. 1.04±0.03; P<0.05) and at 24 weeks (1.96±0.17 vs. 1.12±0.07; P<0.05). The SUVs of 18F-FDG were also significantly greater in the abdominal aorta in the high-fat diet group compared with those in the normal diet group at 16 weeks (1.35±0.08 vs. 1.02±0.02; P<0.05) and at 24 weeks (1.54±0.09 vs. 1.04±0.02; P<0.05). In addition, the SUVs of 18F-FDG in the iliac artery and abdominal aorta were significantly higher at 24 weeks compared with those at 16 weeks in the high-fat diet group (P<0.05). As determined by immunohistochemistry, the percentage of CD68-positive cells in the total number of cells per unit area in each group was 3.20±1.80% in the 24-week normal diet group, 4.70±2.02% in the 16-week high-fat diet group and 6.94±2.02% in the 24-week high-fat diet group; the percentage of CD68-positive cells in the high-fat d iet group at 24 weeks was significantly higher than that in the high-fat diet group at 16 weeks and in the normal diet group at 24 weeks (P<0.05). In conclusion, 18F-FDG PET is a noninvasive imaging tool that can continuously monitor inflammatory lesions of the arterial vessel walls in Wistar rats. Further improvement of the Wistar rat atherosclerosis model may provide data to support the early assessment of and intervention in atherosclerosis. PMID:33732343 | PMC:PMC7903450 | DOI:10.3892/etm.2021.9801 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Sevoflurane alleviates oxygen-glucose deprivation/reoxygenation-induced injury in HT22 cells through regulation of the PI3K/AKT/GSK3β signaling pathway

xlomafota13 shared this article with you from Inoreader Sevoflurane alleviates oxygen-glucose deprivation/reoxygenation-induced injury in HT22 cells through regulation of the PI3K/AKT/GSK3β signaling pathway Via Experimental and therapeutic medicine Exp Ther Med. 2021 Apr;21(4):376. doi: 10.3892/etm.2021.9807. Epub 2021 Feb 19. ABSTRACT Sevoflurane (Sev), a volatile anesthetic, has been reported to exhibit beneficial effects on different ischemia/reperfusion (I/R)-injured organs. However, the neuroprotective effect of Sev on cerebral I/R injury is poorly understood. In the present study, the effects of Sev on HT22 cells exposed to oxygen-glucose deprivation/reperfusion (OGD/R) injury are investigated. The present study demonstrated that OGD/R suppressed the cell viability and increased lactate dehydrogenase (LDH) release from the cells, and these effects were attenuated by Sev treatment. The results also demonstrated that Sev alleviated OGD/R-induced cell apoptosis via flow cytometry and caspase-3 activity determination. Biochemical analysis results revealed that Sev significantly protected against OGD/R-induced oxidative stress by reducing ROS generation and improving antioxidant defense markers. Western blot analysis demonstrated that Sev reactivated the PI3K/AKT/glycogen synthase kinase-3β (GSK3β) signaling pathway, which was inhibited by OGD/R. In addition, wortmannin, a selective PI3K inhibitor was used to investigate the underlying pathways. Notably, the neuroprotective effect of Sev on apoptosis and reactive oxygen species production was found to be suppressed by wortmannin. Collectively, these results demonstrated that Sev may protect neuronal cells against OGD/R-induced injury through the activation of the PI3K/AKT/GSK3β signaling pathway. The findings from the present study provide a novel insight into understanding the neuroprotective effect of Sev on cerebral I/R injury. PMID: 33732349 | PMC:PMC7903476 | DOI:10.3892/etm.2021.9807 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

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.