Long non-coding RNA HOTAIRM1-1 silencing in cartilage tissue induces osteoarthritis through microRNA-125b

xlomafota13 shared this article with you from Inoreader Long non-coding RNA HOTAIRM1-1 silencing in cartilage tissue induces osteoarthritis through microRNA-125b Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):933. doi: 10.3892/etm.2021.10365. Epub 2021 Jul 1. ABSTRACT Aberrations in long noncoding RNA (lncRNA) expression have been recognized in numerous human diseases. In the present study, the of role the long noncoding RNA HOX antisense intergenic RNA myeloid 1 variant (HOTAIRM1-1) in regulating the pathological progression of osteoarthritis (OA) was investigated. The aberrant expression of HOTAIRM1-1 in OA was demonstrated, but the molecular mechanisms require further analysis. The aim of the present study was to explore the function of miR-125b in modulating chondrocyte viability and apoptosis, and to address the functional association between HOTAIRM1-1 and miR-125b as potential targets. A miR-125b inhibitor was used, which laid the foundation for the following investigation. The study confirmed that HOTAIRM1-1 and miR-125b are inversely expressed in chondrocytes. The expression of HOTAIRM1-1 was downregula ted and the expression of miR-125b was upregulated in tissues from patients with OA. HOTAIRM1-1 directly interacted with miR-125b in chondrocytes. HOTAIRM1-1 knockdown was associated with chondrocyte proliferation and extracellular matrix degradation. Furthermore, miR-125b reversed the effect of HOTAIRM1-1 on cell proliferation and apoptosis. In conclusion, the present study indicates that the loss of HOTAIRM1-1 function leads to aberrant increases in the proliferation and apoptosis of chondrocytes. miR-125b may be a potential downstream mechanism that regulates the function of HOTAIRM1-1, and this finding provides a therapeutic strategy for OA. PMID:34306202 | PMC:PMC8280714 | DOI:10.3892/etm.2021.10365 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Role of m6A in osteoporosis, arthritis and osteosarcoma (Review)

xlomafota13 shared this article with you from Inoreader Role of m6A in osteoporosis, arthritis and osteosarcoma (Review) Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):926. doi: 10.3892/etm.2021.10358. Epub 2021 Jun 30. ABSTRACT RNA modification is a type of post-transcriptional modification that regulates important cellular pathways, such as the processing and metabolism of RNA. The most abundant form of methylation modification is RNA N6-methyladenine (m6A), which plays various post-transcriptional regulatory roles in cellular biological functions, including cell differentiation, embryonic development and disease occurrence. Bones play a pivotal role in the skeletal system as they support and protect muscles and other organs, facilitate movement and ensure haematopoiesis. The development and remodelling of bones require a delicate and accurate regulation of gene expression by epigenetic mechanisms that involve modifications of histone, DNA and RNA. The present review discusses the enzymes and proteins involved in mRNA m6A methylation modification and summarises current research progress and the mechanisms of mRNA m6A methylation in common orthopaedic diseases, including osteoporosis, arthritis and osteosarcoma. PMID:34306195 | PMC:PMC8281110 | DOI:10.3892/etm.2021.10358 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

circRNA_103615 contributes to tumor progression and cisplatin resistance in NSCLC by regulating ABCB1

xlomafota13 shared this article with you from Inoreader circRNA_103615 contributes to tumor progression and cisplatin resistance in NSCLC by regulating ABCB1 Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):934. doi: 10.3892/etm.2021.10366. Epub 2021 Jul 1. ABSTRACT Lung cancer is one of the main causes of tumor lethality worldwide. Circular RNAs (circRNAs) have essential roles in tumor progression. However, in non-small cell lung carcinoma (NSCLC), the role of circRNAs remains unknown. In the present study, the expression, function and molecular mechanisms of a new circRNA, circRNA_103615, were investigated in NSCLC. Reverse transcription-quantitative PCR (RT-qPCR) was used to detect circRNA_103615 expression levels in NSCLC and normal tissues, as well as in NSCLC cell lines. MTT assay, flow cytometric assay, colony formation assay, and cell migration and invasion assays were used to examine the function of circRNA_103615 in NSCLC cells. MTT assay, colony formation assay, RT-qPCR, and western blotting were used to detect the effect of circRNA_103615 on cisplatin resistance. The results demonstrated that NSCLC cell lines and tissues had increased levels of circRNA_103615 compared with normal cells and normal tissues, respectively. Functionally, silencing of circRNA_103615 by small interfering RNA resulted in suppression of cell growth, migration, and invasion, but promotion of cell apoptosis. In addition, the cisplatin resistance of NSCLC was reversed by the silencing of circRNA_103615. Notably, ATP binding cassette subfamily Bmember 1 (ABCB1) expression was significantly decreased following circRNA_103615 knockdown, and ABCB1 overexpression reversed the effects of circRNA_103615 silencing on NSCLC cisplatin resistance. Thus, the present study indicated that circRNA_103615 may serve as a critical oncogene and potential novel biomarker in NSCLC, as well as a potential cisplatin resistance promoter, by regulating ABCB1 expression. PMID:34306203 | PMC:PMC8281253 | DOI:10.3892/etm.2021.10366 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Relationship between miRNA-433 and SPP1 in the presence of fracture and traumatic brain injury

xlomafota13 shared this article with you from Inoreader Relationship between miRNA-433 and SPP1 in the presence of fracture and traumatic brain injury Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):928. doi: 10.3892/etm.2021.10360. Epub 2021 Jun 30. ABSTRACT Limb fracture combined with traumatic brain injury (TBI) is one of the most common multiple injuries and patients often suffer from severe craniocerebral injury combined with long bone fracture of the limbs. The present study examined the expression of osteopontin (SPP1) in the tibial fracture callus and heterotopic ossification tissues in craniocerebral injury and investigated its relationship with miR-433. A total of 26 patients with tibial fracture combined with brain injury were included in the TBI group, and 26 patients with simple tibial fracture were included in the control group. The patients received immobilization treatment and callus was collected during the operation. At the time of steel plate removal tissue ossification samples from patients with heterotopic ossification were collected. Peripheral blood was collected from all patient s on the morning of the operation day. Expression of miR-433 and SPP1 mRNA was determined by reverse transcription-quantitative PCR and SPP1 protein expression was measured by western blotting. Dual luciferase reporter assay was used to identify the direct interaction between miR-433 and SPP1 mRNA. The human osteoblast line hFOB1.19 was transfected with agomiR-433 to overexpress miR-433 and expression of SPP1 was also examined. TBI enhanced the incidence of callus formation and heterotopic ossification in patients with fracture but did not alter fracture healing time. SPP1 mRNA and protein expression was elevated in patients who had tibial fracture in combination with craniocerebral injury in comparison with controls By contrast, expression of miR-433 was decreased in patients who had tibial fracture in combination with craniocerebral injury in comparison with controls. miR-433 regulated the expression of SPP1 mRNA and protein by directly binding to the 3'-untranslated region of SPP 1 mRNA. The present study suggests that SPP1 mRNA and protein levels are increased in the callus, heterotopic ossification tissues and plasma from patients with tibial fracture combined with brain injury in comparison with controls. This elevation may be due to the reduced expression of miR-433. PMID:34306197 | PMC:PMC8281207 | DOI:10.3892/etm.2021.10360 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Psoralen accelerates osteogenic differentiation of human bone marrow mesenchymal stem cells by activating the TGF-β/Smad3 pathway

xlomafota13 shared this article with you from Inoreader Psoralen accelerates osteogenic differentiation of human bone marrow mesenchymal stem cells by activating the TGF-β/Smad3 pathway Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):940. doi: 10.3892/etm.2021.10372. Epub 2021 Jul 1. ABSTRACT Psoralen, one of the active ingredients in Psoralea corylifolia, has been previously reported to regulate the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). A previous study revealed that psoralen can regulate the expression levels of microRNA-488 and runt-related transcription factor 2 (Runx2) to promote the osteogenic differentiation of BMSCs. However, the underlying signalling pathway in this process remains to be fully elucidated. BMSCs have also been confirmed to play a key role in the occurrence and development of osteoporosis, and are expected to be potential seed cells in the treatment of osteoporosis. In order to explore the potential signalling pathways of psoralen acting on BMSCs, in the present study, human BMSCs (hBMSCs) were treated with different concentrations of psoralen (0.1, 1, 10 and 100 µmol/l ) and the TGF-β receptor I (RI) inhibitor SB431542 (5 µmol/l) in vitro for 3, 7 or 14 days. Cell Counting Kit-8 and MTT assays were used to measure cell proliferation and cell viability of hBMSCs following psoralen administration. Alkaline phosphatase (ALP) activity and alizarin red S staining were used to assess the osteogenic differentiation ability of hBMSCs. Reverse transcription-quantitative PCR and western blotting were used to measure the expression of osteogenic differentiation-related genes [bone morphogenetic protein 4 (BMP4), osteopontin (OPN), Runx2 and Osterix] and proteins associated with the TGF-β/Smad3 pathway [TGF-β1, TGF-β RI, phosphorylated (p-)Smad and Smad3]. Psoralen was found to increase the proliferation and viability of hBMSCs. Although different concentrations of psoralen enhanced ALP activity and the calcified nodule content in hBMSCs, the enhancement effects were more potent at lower concentrations (0.1, 1 and 10 µmol/l). The expression of BM P4, OPN, Osterix, Runx2, TGF-β1, TGF-β RI and p-Smad3 was also promoted by psoralen at lower concentrations (0.1, 1 and 10 µmol/l). In addition, whilst SB431542 could inhibit calcium deposition and osteogenic differentiation-related gene expression in hBMSCs, psoralen effectively reversed the inhibitory effects of SB431542. In conclusion, psoralen accelerates the osteogenic differentiation of hBMSCs by activating the TGF-β/Smad3 pathway, which may be valuable for the future clinical treatment of osteoporosis. PMID:34306204 | PMC:PMC8281312 | DOI:10.3892/etm.2021.10372 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Salinomycin triggers prostate cancer cell apoptosis by inducing oxidative and endoplasmic reticulum stress via suppressing Nrf2 signaling

xlomafota13 shared this article with you from Inoreader Salinomycin triggers prostate cancer cell apoptosis by inducing oxidative and endoplasmic reticulum stress via suppressing Nrf2 signaling Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):946. doi: 10.3892/etm.2021.10378. Epub 2021 Jul 1. ABSTRACT Salinomycin is a polyether antiprotozoal antibiotic that is widely used as an animal food additive. Some antifungal, antiparasitic, antiviral and anti-inflammatory activities have been reported for salinomycin. Recently, the anti-cancer effect of salinomycin has been demonstrated in breast cancer; however, the underlying mechanism remains unknown. The present study aimed to investigate the functional roles of salinomycin in the progression of prostate cancer cells using the DU145 and PC-3 cell lines. Western blotting and reverse transcription-quantitative polymerase chain reaction were performed to detect the expression of oxidative stress and endoplasmic reticulum stress-related molecules, and flow cytometry was performed to detect the apoptosis rate of DU145 and PC-3 cells after salinomycin treatment. The results demonstrated that salinomycin inh ibited the viability and induced the apoptosis of PC-3 and DU145 cells in a dose-dependent manner. Furthermore, salinomycin increased the production of reactive oxygen species (ROS) and 8-hydroxy-2'-deoxyguanosine (8-OH-dG) and the lipid peroxidation. In addition, salinomycin induced the activation of unfolded protein response and endoplasmic reticulum stress in DU145 and PC-3 cells, as indicated by the elevated expression of binding immunoglobulin protein, activating transcription factor 4, phosphorylated eukaryotic initiation factor 2α, phosphorylated protein kinase RNA-like endoplasmic reticulum kinase and C/EBP homologous protein. In addition, salinomycin significantly downregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1, NAD(P)H quinone dehydrogenase 1 and glutamate-cysteine ligase catalytic subunit and decreased the activity of the antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase in PC-3 and DU145 ce lls. Furthermore, the Nrf2 activator, tert-butylhydroquinone, significantly reversed the therapeutic effects of salinomycin by stimulating the Nrf2 pathway and increasing the activity of antioxidant enzymes. Taken together, these findings demonstrated that salinomycin may trigger apoptosis by inducing oxidative and ER stress in prostate cancer cells via suppressing Nrf2 signaling. PMID:34306210 | PMC:PMC8281384 | DOI:10.3892/etm.2021.10378 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Cell-penetrating heme oxygenase-1 in the therapy of atopic dermatitis in mice

xlomafota13 shared this article with you from Inoreader Cell-penetrating heme oxygenase-1 in the therapy of atopic dermatitis in mice Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):941. doi: 10.3892/etm.2021.10373. Epub 2021 Jul 1. ABSTRACT Atopic dermatitis (AD), also referred to as atopic eczema, is a long-term inflammatory condition that is characterized by itchy, red, swollen and cracked skin. Accumulating evidence suggests that AD is caused by genetic factors, environmental exposure and immune system dysfunction; however, its underlying molecular mechanism remains unclear. Current treatment strategies aim to decrease the severity and frequency of flares. Heme oxygenase-1 (HO-1) is a nuclear factor erythroid 2-related factor 2 (Nrf2)-regulated gene that plays crucial roles against stress, inflammation and oxidation, and exerts cytoprotective effects. Previous studies have reported that treatment of AD induces high expression levels of HO-1 and Nrf2, indicating that HO-1 may play an important role in the treatment of AD. The present study constructed the recombinant protein, cell-p enetrating peptide-HO-1 (CPP-HO-1), which was expressed in Escherichia coli and isolated with a 6xHis-tag using HiTrap His column (1 ml). AD was established using 4-dinitrochlorobenzene (DNCB) in mice. It was observed that the CPP-HO-1 fusion protein decreased the severity of AD, inhibited scratching in mice and decreased skin inflammation. Taken together, the results of the present study suggested that the CPP-HO-1 fusion protein may play a protective role against DNCB-induced AD in mice. PMID:34306205 | PMC:PMC8281355 | DOI:10.3892/etm.2021.10373 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Guillain-Barré syndrome associated with Covid-19: A close relationship or just a coincidence? (Review)

xlomafota13 shared this article with you from Inoreader Guillain-Barré syndrome associated with Covid-19: A close relationship or just a coincidence? (Review) Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):916. doi: 10.3892/etm.2021.10348. Epub 2021 Jun 29. ABSTRACT Several neurological complications affecting the central and peripheral nervous system were described secondary to COVID-19 infection such as hyposmia, headache, nausea, impaired consciousness, psychosis, neurocognitive syndromes and even cerebrovascular accidents. The mechanism of these complications is not fully understood, but heterogenous mechanisms such as cytokine storm, secondary hypercoagulability and direct neurotropism of the virus are thought to be involved. Guillain-Barré syndrome is a heterogeneous disease that frequently follows a bacterial or viral infection. During the ongoing SARS-CoV-2 pandemic, several isolated case reports and case series have suggested an association between this viral infection and the occurrence of Guillain-Barré syndrome. The main mechanism of Guillain-Barré syndrome is probably post-viral dysregulation of the immune system generated by SARS-CoV-2. The clinical characteristics and disease evolution seem to be similar to those observed in Guillain-Barré syndrome secondary to other etiologies. The aim of the present review is to summarize the relevant literature regarding SARS-CoV-2-related Guillain-Barré syndrome. PMID:34306190 | PMC:PMC8281479 | DOI:10.3892/etm.20 21.10348 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Icariin inhibits oral squamous cell carcinoma cell proliferation and induces apoptosis via inhibiting the NF-κB and PI3K/AKT pathways

xlomafota13 shared this article with you from Inoreader Icariin inhibits oral squamous cell carcinoma cell proliferation and induces apoptosis via inhibiting the NF-κB and PI3K/AKT pathways Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):942. doi: 10.3892/etm.2021.10374. Epub 2021 Jul 1. ABSTRACT Oral squamous cell carcinoma (OSCC), one of the most common types of human cancer, has a high mortality rate and a poor prognosis due to its high rates of recurrence and metastasis. In recent years, icariin (ICA) has been reported to play an important role in a variety of malignancies, such as gastric, colorectal, pancreatic and ovarian cancer. However, its role and mechanism in OSCC remains to be elucidated. The present study aimed to investigate the effect of ICA in OSCC cells and to reveal its underlying mechanisms. The OSCC cell lines SCC9 and Cal 27 were used to explore the effect of different concentrations of ICA on the biological behavior of OSCC cells. The effect of ICA on OSCC cell proliferation and apoptosis was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide and flow cytometric assays, respectively. Sub sequently, the protein expression levels of caspase-3 and cleaved-caspase-3 were detected using western blot analysis. Additionally, the protein and mRNA expression levels of nuclear factor-κB (NF-κB) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway-related factors were determined using western blot analysis and reverse transcription-quantitative PCR, respectively. The results demonstrated that ICA inhibited OSCC cell proliferation and significantly increased the apoptosis rate in a dose-dependent manner. In addition, treatment of OSCC cells with ICA upregulated the protein expression of cleaved-caspase-3 and increased the cleaved-caspase-3/caspase-3 ratio. The protein expression levels of phosphorylated (p)-p65, p-PI3K and p-AKT were decreased in OSCC cells treated with ICA. The aforementioned findings revealed that ICA could attenuate the proliferation of OSCC cells and induce apoptosis via inhibiting the NF-κB and PI3K/AKT signaling pathways. T herefore, the current study provided a new insight into the clinical treatment of OSCC. PMID:34306206 | PMC:PMC8281471 | DOI:10.3892/etm.2021.10374 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Clinical characteristics and survival of patients with three major connective tissue diseases associated with pulmonary hypertension: A study from China

xlomafota13 shared this article with you from Inoreader Clinical characteristics and survival of patients with three major connective tissue diseases associated with pulmonary hypertension: A study from China Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):925. doi: 10.3892/etm.2021.10357. Epub 2021 Jun 30. ABSTRACT The present cross-sectional study investigated the clinical characteristics and survival of patients with three types of connective tissue disease associated with pulmonary hypertension (CTD-PH) diagnosed early by echocardiography. A total of 218 patients with CTD-PH were included in the present study. Patients with the three major types of CTD, namely systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and primary Sjögren's syndrome (pSS), were included. PH was diagnosed based on pulmonary arterial systolic pressure >35 mmHg, as measured by Doppler echocardiography. Demographic data, clinical features, laboratory results and echocardiographic parameters were collected and analyzed. The Kaplan-Meier method was used to calculate survival rates. Multivariate analysis was used to identify independent factors affecting mortality. Compared with patients with CTD with pSS (6.5%) or SLE (3.8%), those with SSc had a higher prevalance of PH (12.9%). Patients with SSc-PH had the highest rate of lung involvement (81.2%) and 42.2% of patients were classified as World Health Organization-function class III/IV at the time of diagnosis with PH. The overall survival rate among patients with CTD-PH at 1, 3 and 5 years was 81.4, 72.4 and 56.9%, respectively. Patients with SLE-PH appeared to have the most favorable prognosis and patients with SSc-PH had the poorest relative outcomes. Multivariate analysis revealed that age ≥50 years was the only independent risk factor for mortality. In conclusion, among the patients with CTDs investigated, the prevalence of PH was highest among those with SSc. Patients with SSc-PH had the highest prevalence of pulmonary involvement, the lowest survival rate and the worst prognosis. PMID:34306194 | PMC:PMC8280713 | DOI:10.3892/etm.2021.10357 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.