Vicenin 3 ameliorates ECM degradation by regulating the MAPK pathway in SW1353 chondrocytes

xlomafota13 shared this article with you from Inoreader Vicenin 3 ameliorates ECM degradation by regulating the MAPK pathway in SW1353 chondrocytes Via Experimental and therapeutic medicine Exp Ther Med. 2021 Dec;22(6):1461. doi: 10.3892/etm.2021.10896. Epub 2021 Oct 20. ABSTRACT Aberrant destruction of the articular extracellular matrix (ECM) has been considered to be one of the pathological features of osteoarthritis (OA) which results in chondrocyte changes and articular cartilage degeneration. The MAPK signaling pathway serves a key role by releasing cartilage-degrading enzymes from OA chondrocytes. However, the use of MAPK inhibitors for OA is hindered by their potential long-term toxicity. Vicenin 3 is one of the major components of the Jian-Gu injection which is effective in the clinical treatment of OA. However, its potential impact on OA remain poorly understood. Therefore, the present study aimed to assess the effects of vicenin 3 on interleukin (IL)-1β-treated SW1353 chondrocytes, which mimic the microenvironment of OA. These chondrocytes were pretreated with vicenin 3 (0, 5 and 20 µM) for 1 h and subsequentl y stimulated with IL-1β (10 ng/ml) for 24 h. Nitric oxide (NO) production was measured using the Griess reaction, whereas the production of prostaglandin E2 (PGE2), matrix metalloproteinases (MMPs), A disintegrin-like and metalloproteinase with thrombospondin motifs (ADAMTSs), collagen type II and aggrecan were measured using ELISA. The mRNA expression of MMPs and ADAMTSs were measured using reverse transcription-quantitative PCR. The protein expression levels of MAPK were measured using western blotting. Vicenin 3 was found to significantly inhibit IL-1β-induced production of NO and PGE. Increments in the expression levels of MMP-1, MMP-3, MMP-13, ADAMTS-4 and ADAMTS-5 induced by IL-1β, in addition to the IL-1β-induced degradation of collagen type II and aggrecan, were all reversed by vicenin 3 treatment. Furthermore, vicenin 3 suppressed IL-1β-stimulated MAPK activation, an effect that was similar to that exerted by SB203580, a well-known p38 MAPK inhibitor. In conclusion, vi cenin 3 may confer therapeutic potential similar to that of the p38 MAPK inhibitor for the treatment of OA. PMID:34737801 | PMC:PMC8561762 | DOI:10.3892/etm.2021.10896 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Identification of potential novel biomarkers for abdominal aortic aneurysm based on comprehensive analysis of circRNA-miRNA-mRNA networks

xlomafota13 shared this article with you from Inoreader Identification of potential novel biomarkers for abdominal aortic aneurysm based on comprehensive analysis of circRNA-miRNA-mRNA networks Via Experimental and therapeutic medicine Exp Ther Med. 2021 Dec;22(6):1468. doi: 10.3892/etm.2021.10903. Epub 2021 Oct 21. ABSTRACT Abdominal aortic aneurysm (AAA) is a life-threatening disorder and, therefore, investigation into its underlying mechanisms in light of the competing endogenous RNAs (ceRNAs) hypothesis has gradually increased. However, there is still lacking systematic analysis on AAA-associated circular RNA (circRNA)-microRNA (miRNA/miR)-messenger RNA (mRNA) interaction networks based on bioinformatics methods. The present study attempted to identify novel molecular biomarkers for AAA by profiling circRNA-miRNA-mRNA networks using three public microarray datasets (GSE7084, GSE57691 and GSE144431). A total of 135 differentially expressed genes (DEGs) and 142 differentially expressed circRNAs were detected using the limma R package with the statistical threshold of P<0.05 and |log2fold change (FC)| >1.5. In addition, 12 circRNA-miRNA-mRNA axes we re identified to construct upregulated and downregulated ceRNA networks using Cytoscape. Based on molecular complex detection algorithm, (hsa_circ_0057691/0092108/0006845/0082182)- miR-330-5p-calponin 1 (CNN1) and (hsa_circ_0061482/0011450/0008351/0004121)-miR-326-CD8a molecule (CD8A) were recognized as the center axes in ceRNA networks. Reverse transcription-quantitative PCR results verified the significant downregulation of CNN1 and upregulation of CD8A in human AAA tissues (P<0.05). In addition, four upregulated circRNA/mRNA axes, and five downregulated circRNA/mRNA axes were revealed to have possible biological functions in the pathogenesis of AAA using the Cytoscape software. Receiver operating characteristic analysis demonstrated the accuracy of these nine DEGs involved in these axes for AAA diagnosis with area under the curves >0.80. The present study revealed novel circRNA-miRNA-mRNA networks associated with AAA, especially for CNN1 and CD8A axes with the potential fun ction of 'focal adhesion' and 'immune response', respectively. Overall, the present findings may provide evidence to explore the implicated ceRNAs in the molecular mechanisms and as novel biomarkers for AAA. PMID:34737808 | PMC:PMC8561771 | DOI:10.3892/etm.2021.10903 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Mechanism and prevention strategy of a bidirectional relationship between heart failure and cancer (Review)

xlomafota13 shared this article with you from Inoreader Mechanism and prevention strategy of a bidirectional relationship between heart failure and cancer (Review) Via Experimental and therapeutic medicine Exp Ther Med. 2021 Dec;22(6):1463. doi: 10.3892/etm.2021.10898. Epub 2021 Oct 20. ABSTRACT The relationship between cancer and heart failure has been extensively studied in the last decade. These studies have focused on describing heart injury caused by certain cancer treatments, including radiotherapy, chemotherapy and targeted therapy. Previous studies have demonstrated a higher incidence of cancer in patients with heart failure. Heart failure enhances an over-activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system, and subsequently promotes cancer development. Other studies have found that heart failure and cancer both have a common pathological origin, flanked by chronic inflammation in certain organs. The present review aims to summarize and describe the recent discoveries, suggested mechanisms and relationships between heart failure and cancer. The current review provides more ideas on clinical p revention strategies according to the pathological mechanism involved. PMID:34737803 | PMC:PMC8561773 | DOI:10.3892/etm.2021.10898 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

miR-199b-5p mediates adriamycin-induced podocyte apoptosis by inhibiting the expression of RGS10

xlomafota13 shared this article with you from Inoreader miR-199b-5p mediates adriamycin-induced podocyte apoptosis by inhibiting the expression of RGS10 Via Experimental and therapeutic medicine Exp Ther Med. 2021 Dec;22(6):1469. doi: 10.3892/etm.2021.10904. Epub 2021 Oct 21. ABSTRACT Podocyte apoptosis is a key risk factor for the progression of kidney diseases. MicroRNA (miR)-199b-5p has been shown to be involved in cell apoptosis. However, the molecular mechanisms of miR-199b-5p in podocyte apoptosis remain uncertain. Thus, the present study aimed to investigate whether miR-199b-5p participates in the regulation of podocyte apoptosis and to elucidate the involved mechanisms of this process. A podocyte apoptosis model was constructed using adriamycin (ADR) in vitro. miR-199b-5p mimic and inhibitor were transfected in podocytes to change the expression level of miR-199b-5p. RNA expression was examined by reverse transcription-quantitative PCR. Western blotting was used to measure protein expression. Apoptosis was monitored via flow cytometry and detection of apoptosis-associated proteins. The results from the present s tudy demonstrated that miR-199b-5p was upregulated and that regulator of G-protein signaling 10 (RGS10) was downregulated in ADR-stimulated podocytes. Overexpression of miR-199b-5p could inhibit RGS10 expression and stimulate podocyte apoptosis, whereas miR-199b-5p knockdown restored the levels of RGS10 and ameliorated podocyte apoptosis in ADR-induced podocytes. Furthermore, the effects of miR-199b-5p overexpression could be significantly reversed by RGS10 overexpression. In addition, podocyte transfection of miR-199b-5p activated the AKT/mechanistic target of rapamycin (mTOR) signaling, which was blocked following RGS10 overexpression. Taken together, the present study demonstrated that miR-199b-5p upregulation could promote podocyte apoptosis by inhibiting the expression of RGS10 through the activation of AKT/mTOR signaling. PMID:34737809 | PMC:PMC8561778 | DOI:10.3892/etm.2021.10904 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Transient receptor potential ankyrin 1 and calcium: Interactions and association with disease (Review)

xlomafota13 shared this article with you from Inoreader Transient receptor potential ankyrin 1 and calcium: Interactions and association with disease (Review) Via Experimental and therapeutic medicine Exp Ther Med. 2021 Dec;22(6):1462. doi: 10.3892/etm.2021.10897. Epub 2021 Oct 20. ABSTRACT Calcium (Ca2+) is an essential signaling molecule in all cells. It is involved in numerous fundamental functions, including cell life and death. Abnormal regulation of Ca2+ homeostasis may cause human diseases. Usually known as a member of the transient receptor potential (TRP) family, TRP ankyrin 1 (TRPA1) is the only member of the ankyrin subfamily identified in mammals so far and widely expressed in cells and tissues. As it is involved in numerous sensory disorders such as pain and pruritus, TRPA1 is a potential target for the treatment of neuropathy. The functions of TRP family members are closely related to Ca2+. TRPA1 has a high permeability to Ca2+, sodium and potassium ions as a non-selective cation channel and the Ca2+ influx mediated by TRPA1 is involved in a variety of biological p rocesses. In the present review, research on the relationship between the TRPA1 channel and Ca2+ ions and their interaction in disease-associated processes was summarised. The therapeutic potential of the TRPA1 channel is highlighted, which is expected to become a novel direction for the prevention and treatment of health conditions such as cancer and neurodegenerative diseases. PMID:34737802 | PMC:PMC8561754 | DOI:10.3892/etm.2021.10897 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Anagliptin alleviates lipopolysaccharide-induced inflammation, apoptosis and endothelial dysfunction of lung microvascular endothelial cells

xlomafota13 shared this article with you from Inoreader Anagliptin alleviates lipopolysaccharide-induced inflammation, apoptosis and endothelial dysfunction of lung microvascular endothelial cells Via Experimental and therapeutic medicine Exp Ther Med. 2021 Dec;22(6):1472. doi: 10.3892/etm.2021.10907. Epub 2021 Oct 22. ABSTRACT It has been reported that dipeptidyl peptidase-4 (DPP4) inhibition protects against acute lung injury (ALI). Anagliptin is a novel selective inhibitor of DPP4 but its role in ALI has not been studied. The present study aimed to investigate the effects of anagliptin on lipopolysaccharide (LPS)-induced human pulmonary microvascular endothelial cell (HPMVEC) injury, as well as its underlying mechanism. HPMVECs were exposed to LPS in the presence or absence of anagliptin co-treatment. MTT assay was used to evaluate cell viability and nitric oxide (NO) production was detected using a commercial kit. DPP4 and pro-inflammatory cytokine expression levels, apoptosis and migration were assessed via reverse transcription-quantitative PCR, western blotting, TUNEL staining and wound healing assay, respectively. Western blot analysis was performed to assess ex pression levels of proteins involved in NF-κB signaling, cell apoptosis and migration, as well as high mobility group box 1 (HMGB1)/receptor for advanced glycation end products (RAGE). LPS decreased cell viability and NO production, but elevated expression of DPP4 in HPMVECs. LPS promoted pro-inflammatory cytokine expression, NF-κB activation and cell apoptosis, but inhibited cell migration and phosphorylated-AKT/endothelial NO synthase expression. Anagliptin co-treatment significantly restored all of these effects. Mechanistically, the upregulation of HMGB1/RAGE expression induced by LPS was markedly blocked by anagliptin. In conclusion, anagliptin alleviated inflammation, apoptosis and endothelial dysfunction in LPS-induced HPMVECs via modulating HMGB1/RAGE expression. These data provide a basis for use of anagliptin in ALI treatment. PMID:34737812 | PMC:PMC8561766 | DOI:10.3892/etm.2021.10907 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Cognitive Mechanisms in Pediatric Voice Therapy – An Initial Examination

xlomafota13 shared this article with you from Inoreader Cognitive Mechanisms in Pediatric Voice Therapy – An Initial Examination Via Journal of Voice Voice disorders are a common communication disorder in children. Behavioral voice therapy is recommended by both Otolaryngologists and Speech-Language Pathologists as a first-line approach for treatment of benign vocal fold lesions that affect children in large numbers. However, the role of cognitive mechanisms critical to voice therapy have not yet been explored. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.