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Πέμπτη 28 Οκτωβρίου 2021

Influence of extracellular nanovesicles derived from adipose-derived stem cells on nucleus pulposus cell from patients with intervertebral disc degeneration

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Exp Ther Med. 2021 Dec;22(6):1431. doi: 10.3892/etm.2021.10866. Epub 2021 Oct 11.

ABSTRACT

An increasing number of individuals are suffering from lower back and neck pain caused by intervertebral disc degeneration each year. Although the application of mesenchymal stem cells (MSCs) has provided desirable results in the treatment of intervertebral disc degeneration, there are multiple risks associated with the directed application of MSCs. An increasing number of studies have suggested that stem cells, through the release of extracellular nanovesicles, have vital functions in tissue regeneration and repair with low risk. The present study investigated the effect of extracellular nanovesicles derived from adipose-derived stem cells (ADSCs) on nucleus pulposus (NP) cells from patients with intervertebral disc degeneration. Human NP cells were obtained from patients with intervertebral disc degeneration undergoing surgical procedures in ad dition to ADSCs from liposuction patients. ADSC-derived extracellular nanovesicles were isolated and characterized. The differentiation and biological activity of NP cells cultured with or without ADSC-derived extracellular nanovesicles were assessed and inflammatory factors and intervertebral disc degeneration-associated markers were also measured. The results indicated that extracellular nanovesicles derived from ADSCs increased the migration and proliferation of NP cells and inhibited inflammatory activity, suggesting their utility for the treatment of intervertebral disc degeneration.

PMID:34707712 | PMC:PMC8543194 | DOI:10.3892/etm.2021.10866

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Comparative study on the biological characteristics of menstrual blood- and endometrium-derived endometrial cells

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Exp Ther Med. 2021 Dec;22(6):1421. doi: 10.3892/etm.2021.10856. Epub 2021 Oct 11.

ABSTRACT

During a woman's reproductive period, the endometrial tissue is shed and regenerated every month to prepare for pregnancy or for the next cycle. The aim of the present study was to isolate, culture and characterize human endometrial cells (ECs) derived from menstrual blood (MB) and the endometrium (E). MB-derived ECs (MB-ECs) were isolated from women's MB. E-derived ECs (E-ECs) were isolated from women's endometrial tissues. The present study investigated the epithelial cell marker cytokeratin 18 (CK18) in MB-ECs and E-ECs. Cell proliferation analyses indicated that E-ECs (population doubling time, 20.85 h) grew faster than MB-ECs (population doubling time, 22.05 h; P<0.05). Cell migration ability was found to be significantly greater for MB-ECs than for E-ECs at 48 h (P<0.01). MB-ECs incubated with TGF-β1 (3 ng/ml) exhibited significantly decreased CK18 mRNA expression (P<0.01), and significantly increased vimentin (Vim) mRNA (P<0.05) and protein (P<0.01) expression at 6 and 12 h, respectively. E-EC incubation with TGF-β1 (3 ng/ml) significantly decreased CK18 mRNA expression (P<0.01) at 12 h and significantly increased Vim mRNA (P<0.01) and protein expression (P<0.05) at 6 h. The present results indicated that MB-ECs and E-ECs were biologically different, and that epithelial-mesenchymal transdifferentiation could be induced by TGF-β1 treatment.

PMID:34707703 | PMC:PMC8543186 | DOI:10.3892/etm.2021.10856

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Mechanism underlying circularRNA_014301-mediated regulation of neuronal cell inflammation and apoptosis

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Exp Ther Med. 2021 Dec;22(6):1432. doi: 10.3892/etm.2021.10867. Epub 2021 Oct 11.

ABSTRACT

Spinal cord injury (SCI) causes damage to the spinal cord owing to trauma or disease and myelinated fiber tracts that transmit sensation and motor signals to and from the brain. Circular RNAs (circRNAs) are a recently discovered class of regulatory molecules, and their roles in SCI are still unknown. circRNA_014301 was indicated to be differentially expressed in the spinal cord at the site of SCI in a rat model. To analyze the role of circRNA_014301 in SCI, we exposed rat adrenal pheochromocytoma PC12 cells were exposed to increasing concentrations of lipopolysaccharide (LPS) and to construct a PC12 cell inflammatory model. Cell Counting Kit-8 assay was used to analyze cell viability. Reverse transcription-quantitative PCR and ELISA were used to detect the expression of inflammatory factors (IL-1β, IL-6 and TNF-α). Annexin V-FITC/PI double stai ning was employed to detect cell apoptosis, and western blotting was performed to detect the expression of apoptotic proteins (Bax/Bcl-2/cleaved caspase-3) and NF-κB. The results demonstrated that LPS induced inflammation in PC12 cells as evidenced by the reduced cell proliferation and enhanced expression of inflammatory and apoptotic factors under increasing LPS concentrations. Western blotting analyses indicated that circRNA_014301 induced the expression of p-NF-κB/NF-κB, Bax and cleaved caspase-3, and decreased the expression of Bcl-2 following LPS-induced inflammation, and this apoptosis-promoting effect was relieved by small interfering-RNA-mediated knockdown of circRNA_014301. Thus, circRNA_014301 silencing alleviated apoptosis and inflammation in PC12 cells. SCI is invariably associated with spinal cord inflammation, and LPS was used to stimulate apoptosis and inflammatory injury in PC12 cells, and create a cell model of SCI. By promoting PC12 cell apoptosis under inflamma tory conditions, it was indicated that circRNA_014301 may suppress SCI. Therefore, circRNA_014301 may represent a potential target for SCI diagnosis and therapy.

PMID:34707713 | PMC:PMC8543437 | DOI:10.3892/etm.2021.10867

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MicroRNA-216a-5p in lipopolysaccharide-induced endothelial injury

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Exp Ther Med. 2021 Dec;22(6):1426. doi: 10.3892/etm.2021.10861. Epub 2021 Oct 11.

ABSTRACT

MicroRNAs (miRNAs/miRs) are a type of non-coding RNA that are closely associated with disease development and treatment. The present study aimed to investigate the role of miR-216a-5p in lipopolysaccharide (LPS)-induced endothelial injury in vitro. The EdU assay was performed to detect EdU-positive cells, while flow cytometric analysis was performed to detect apoptotic cells. Reverse transcription-quantitative PCR and western blot analyses were performed to detect the expression levels of miR-216a-5p, Toll-like receptor 4 (TLR4), MyD88 and nuclear factor (NF)-κB(p65) and phosphorylated (p)-NF-κB(p65). Furthermore, p-NF-κB(p65) nuclear expression level was detected via cellular immunofluorescence. The dual-luciferase reporter assay was performed to verify the association between miR-216a-5p and TLR4. The results demonstrated that the num ber of EdU-positive cells significantly decreased, the apoptotic rate significantly increased, and TLR4, MyD88 and NF-κB(p65) mRNA expression levels were significantly upregulated.TLR4, MyD88 and p-NF-κB(p65) protein expression levels were significantly upregulated and p-NF-κB(p65) nuclear concentration was significantly enhanced in the small interfering RNA-miR-216a-5p and LPS groups (P<0.001, respectively) compared with the negative control group. However, the addition of miR-216a-5p significantly increased the number of EdU-positive cells, significantly decreased the apoptotic rate and significantly downregulated the mRNA expression levels of TLR4, MyD88 and NF-κB(p65), as well as the protein expression levels of TLR4, MyD88 and p-NF-κB(p65). In addition, the p-NF-κB(p65) nuclear concentration was significantly decreased in the miR-216a-5p group (P<0.001, respectively) compared with the LPS group. Taken together, the results suggest that overexpression of miR-216a-5p suppresses the effects of LPS induced endothelial injury.

PMID:34707707 | PMC:PMC8543236 | DOI:10.3892/etm.2021.10861

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Irisin attenuates inflammation in a mouse model of ulcerative colitis by altering the intestinal microbiota

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Exp Ther Med. 2021 Dec;22(6):1433. doi: 10.3892/etm.2021.10868. Epub 2021 Oct 11.

ABSTRACT

Evidence has demonstrated that the gut microbiota, which consists of probiotics and pathogenic microorganisms, is involved in the initiation of ulcerative colitis (UC) via the dysregulation of intestinal microflora and normal immune interactions, which ultimately leads to intestinal mucosal dysfunction. Irisin is released from muscle cells and displays anti-inflammatory effects; however, the mechanisms underlying irisin-mediated anti-inflammatory effects in UC have not been previously reported. In the present study, mice were divided into the following four groups: i) Control; ii) irisin; iii) dextran sulfate sodium (DSS) salt; and iv) DSS + irisin. Subsequently, the effects of irisin were investigated by observing alterations in intestinal microbes. Irisin significantly reduced the degree of inflammation in UC by reversing alterations to the mac roscopic score, histological score, number of CD64+ cells and inflammatory cytokine alterations (P<0.05). Analysis of the microbial diversity in the stools of mice with active UC indicated that the five bacteria that displayed the greatest alterations in relative abundance were Alloprevotella, Bacteroides, Lachnospiraceae-UCG-001, Prebotellaceae-UCG-001 and Rikenellaceae-RCB-gut-group. Furthermore, Bactoroides were positively correlated with the histopathological score (P=0.001; R=0.977) and interleukin (IL)-23 levels (P=0.008; R=0.924). Alloprevotella (P=0.001; R=-0.943), Lachnospiraceae-UCG-001 (P=0.000; R=-0.973) and Rikenollaceae-RC8-gut-group (P=0.001; R=-0.971) were negatively correlated with the histopathological score. Furthermore, Lachnospiraceae-UCG-001 (P=0.01; R=-0.873) and Rikenollaceae-RC8-gut-group (P=0.049; R=-0.814) were negatively correlated with IL-23 levels. In summary, the results of the prese nt study suggested that irisin improved inflammation in a UC mouse model potentially via altering the gut microbiota.

PMID:34707714 | PMC:PMC8543469 | DOI:10.3892/etm.2021.10868

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Use of optical coherence tomography in orthodontics

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Exp Ther Med. 2021 Dec;22(6):1424. doi: 10.3892/etm.2021.10859. Epub 2021 Oct 11.

ABSTRACT

Optical coherence tomography (OCT) is a modern imaging method with applicability in orthodontics. In recent years, there has been an increasing trend in the use of ceramic brackets. The aim of the present study was to investigate the effects of bonding metallic and ceramic brackets on tooth enamel, using optical coherence tomography. For this purpose, 20 permanent teeth we bonded and were subsequently debonded using a side cutter or anterior bracket removal pliers. Using the OCT technique, the enamel, the amount of adhesive remaining and the bracket fragments remaining on the tooth surface were analyzed following the debonding procedure. It was demonstrated that enamel cracks were present only in the samples bonded with ceramic brackets. At the same time, it was noted that the type of pliers did not affect the incidence and extent of damage to th e enamel. The type of debonding technique (using the side cutter or the anterior removal pliers) used did not markedly affect the amount of adhesive remaining on the teeth. Thus, as demonstrated herein, by analyzing the enamel structure through the use of OCT, the quality of the processes and the materials used for manufacturing brackets can be increased.

PMID:34707705 | PMC:PMC8543239 | DOI:10.3892/etm.2021.10859

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Kidney injury molecule-1 levels are associated with therapeutic outcomes and renal tubulointerstitial injury severity in idiopathic membranous nephropathy

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Exp Ther Med. 2021 Dec;22(6):1434. doi: 10.3892/etm.2021.10869. Epub 2021 Oct 11.

ABSTRACT

Kidney injury molecule-1 (KIM-1) has an important role in chronic kidney disease development. The present study aimed to retrospectively analyze patients with idiopathic membranous nephrology (IMN) with different therapeutic outcomes to investigate the association between KIM-1 levels and therapeutic outcomes. A total of 51 patients with IMN and 20 healthy controls were included. Patients were classified into three groups: Spontaneous remission, remission with immunosuppressive therapy (IST) and nonremission with IST. Clinical and biochemical variables were collected. Urinary KIM-1 levels were measured by ELISA and renal KIM-1 expression was evaluated by immunohistochemistry. Patients with IMN were characterized as having elevated urinary and renal KIM-1 levels compared with those in the controls. Significantly increased urinary and renal KIM-1 l evels were observed in the nonremission with IST group compared with those in the spontaneous remission group, and the same trend was observed for the plasma anti-podocyte antigen phospholipase A2 receptor antibody levels. Patients with more severe tubular injury (T2 index) presented with significantly higher urinary and renal KIM-1 levels than those with the T0 index. Urinary and renal KIM-1 levels were positively correlated with blood urea nitrogen, serum creatinine, serum cystatin-C, urinary albumin/creatinine ratio, urinary β2-microglobulin and the renal interstitial fibrosis index, and they were negatively correlated with serum albumin. Furthermore, urinary KIM-1 levels were positively correlated with the renal KIM-1 levels. In conclusion, the measurement of urinary and renal KIM-1 levels may be helpful in guiding medication selection and predicting therapeutic outcomes for patients with IMN.

PMID:34707715 | PMC:PMC8543435 | DOI:10.3892/etm.2021.10869

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Adipose-derived mesenchymal stem cell exosomes inhibit transforming growth factor-β1-induced collagen synthesis in oral mucosal fibroblasts

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Exp Ther Med. 2021 Dec;22(6):1419. doi: 10.3892/etm.2021.10854. Epub 2021 Oct 11.

ABSTRACT

Oral submucosal fibrosis (OSF) is a potentially malignant oral disorder that requires the further development of advanced treatment strategies. TGF-β1 has been reported to be the main trigger for the increased collagen production and reduced activity of matrix degradation pathways in OSF. Exosomes are key mediators of paracrine signaling that have been proposed for direct use as therapeutic agents for tissue repair and regeneration. The present study aimed to investigate the effects of human adipose-derived mesenchymal stem cell (ADSC) exosomes (ADSC-Exos) on TGF-β1-treated oral fibroblasts in vitro and to unravel the potential underlying mechanism of action. Oral mucosal fibroblasts were obtained from the buccal tissues of patients without OSF during extraction of the third molar. ADSCs were obtained from three healthy female individual s during liposuction procedures. ADSC-Exos were isolated by ultracentrifugation and identified by electron microscopy, nanoparticle tracking and western blotting. Immunofluorescence and immunocytochemistry staining were performed to measure the expression levels of vimentin and α-smooth muscle actin in the fibroblasts. Reverse transcription-quantitative PCR and western blotting were used to determine the expression levels of mRNAs and proteins associated with collagen production. The p38 MAPK activator anisomycin was used to identify the underlying mechanisms of the effects of ADSC-Exos on TGF-β1-induced collagen synthesis in oral mucosal fibroblasts. The results of the present study revealed that ADSC-Exos exhibited a cup- or sphere-shaped morphology, with a mean diameter of 58.01±16.17 nm. ADSC-Exos were also found to be positive for CD63 and tumor susceptibility 101 expression. ADSC-Exos treatment reversed the TGF-β1-induced upregulation of collagen I and III protein expressi on. In addition, in the presence of TGF-β1, the expression levels of collagen type I α 1 chain and collagen type III α 1 chain mRNA were downregulated, whilst the expression levels of matrix metalloproteinase (MMP)1 and MMP3 were upregulated following ADSC-Exos treatment. The TGF-β1-induced upregulation in the phosphorylation of p38 in addition to the increased protein expression of collagens I and III were also reversed in fibroblasts following ADSC-Exos treatment. However, anisomycin treatment alleviated these ADSC-Exos-induced changes. In conclusion, findings from the present study suggest that ADSC-Exos may represent a promising strategy for OSF treatment by targeting the p38 MAPK signaling pathway.

PMID:34707701 | PMC :PMC8543178 | DOI:10.3892/etm.2021.10854

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Case 33-2021: A 68-Year-Old Man with Painful Mouth Ulcers

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A 68-year-old man was admitted with painful mouth ulcers and weight loss of 6 weeks' duration. The ulcers had worsened despite treatment with acyclovir, prednisone, and colchicine. The blood eosinophil count was increased, and the patient was positive for the HLA-B51 allele. A diagnostic procedure was performed.


Behçet's disease (BD) has been known to be strongly associated with the human leukocyte antigen (HLA) B51. This B51 association has been confirmed in many different ethnic groups between the Middle East and Japan, and it has been proposed that BD is prevalent in those ethnic groups along the old Silk Route.

Presentation of Case. Dr. Ian D. Cooley (Medicine): A 68-year-old man was admitted to this hospital because of painful mouth ulcers and weight loss. The patient had been well until 6 weeks before the current admission, when painful mouth ulcers and neck pain developed. He was evaluated at an urgent…
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Midline crossing pulmonary vein: right upper lobe dual venous drainage, with partial anomalous venous return of the right lung into a persistent left superior vena cava

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Surg Radiol Anat. 2021 Oct 28. doi: 10.1007/s00276-021-02849-9. Online ahead of print.

ABSTRACT

INTRODUCTION: We present a case of dual drainage of the right upper lobe of the lung into the left atrium and via partial anomalous venous pulmonary return (PAPVR) into a persistent left superior vena cava (SVC).

DISCUSSION: It is only in the minority of PAPVR cases where the anomalous pulmonary veins cross the midline. We provide a review of current literature on this topic and an explanatory embryological model. Knowledge of embryonic development and possible anatomic variations, including the concept of dual venous drainage of the lung, leads to better interpretation of imaging, with more accurate description of the morphology at hand. High-resolution multidetector computed tomography (MDCT) helps to delineate the exact vascular anatomy. This will enhance a better understanding of and anticipation on the patient's disease status, with more accurate planning of intervention, and possibly less complications.

PMID:34709422 | DOI:10.1007/s00276-021-02849-9

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