Regulatory role of miRNA-23a in diabetic retinopathy

xlomafota13 shared this article with you from Inoreader Regulatory role of miRNA-23a in diabetic retinopathy Via Experimental and therapeutic medicine Exp Ther Med. 2021 Dec;22(6):1477. doi: 10.3892/etm.2021.10912. Epub 2021 Oct 25. ABSTRACT The present study aimed to investigate the expression of microRNA (miRNA)-23a in blood and tear samples from diabetic retinopathy (DR) patients. Blood and tear samples were obtained from 33 patients with proliferative DR. Additionally, a rat model of DR was established. Reverse transcription-quantitative PCR was used to determine vascular endothelial growth factor (VEGF) mRNA and miRNA-23a expression levels, while ELISA and western blot analysis were performed to determine protein expression levels. Bioinformatics analysis and dual luciferase reporter assay were used to predict and validate the interaction between miRNA-23a and VEGF and cell proliferative ability was assessed with the MTT assay. In comparison to control patients VEGF mRNA and protein expression levels were significantly elevated in the blood and tear samples from patients with DR , while the expression level of miRNA-23a was significantly reduced. In blood and retinal tissues from a rat model of DR, the mRNA and protein expression levels of VEGF were significantly increased, while the miRNA-23a expression level was significantly decreased relative to controls. Dual luciferase reporter assay showed that miRNA-23a bound to the 3'-untranslated region (UTR) of VEGF. Moreover, over-expression of miRNA-23a significantly reduced the expression level of VEGF and the proliferative activity of human retinal microvascular endothelial cells. The elevated VEGF expression in the blood and tears of patients with DR may be related to the reduced miRNA-23a expression. miRNA-23a may regulate microvascular growth at the retina via VEGF and contribute to DR progression. PMID:34765018 | PMC:PMC8576621 | DOI:10.3892/etm.2021.10912 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Prognostic value of the location of submucosal uterine leiomyomas in infertility

xlomafota13 shared this article with you from Inoreader Prognostic value of the location of submucosal uterine leiomyomas in infertility Via Experimental and therapeutic medicine Exp Ther Med. 2021 Dec;22(6):1482. doi: 10.3892/etm.2021.10917. Epub 2021 Oct 25. ABSTRACT Submucosal fibroid location and size are predictive factors of impaired fertility. Submucosal fibroids cause infertility through several mechanisms including distortion of the endometrial cavity, increased uterine contractility, local inflammation and remodeling of the endometrial blood supply. This is a monocentric, retrospective, cross-sectional study, conducted in the Department of Obstetrics and Gynecology of 'Sf. Pantelimon' Clinical Emergency Hospital, analyzing patients from a 5-year period (January 2015-December 2019). In the present study, the relationship between different characteristics of the submucosal fibroids (among others, location and dimensions) and fertility (birth rates, early pregnancy loss rates) were investigated. This study identified that submucosal and intramural fibroids are risk factors for reduced birth rate compared with subserosal fibroids (P=0.02, RR=2.58, 95% CI 1.03-6.47; P=0.005, RR=1.18, 95% CI 1.02-1.35, respectively). In addition, G2 leiomyomas are risk factors for low birth rate compared with G0 and G1 fibroids (P=0.01, RR=1.95, 95% CI 1.05-3.60). Moreover, the presence of a subserosal fibroid was associated with an increased early pregnancy loss rate (P=0.01, RR=2.14, 95% CI 1.05-4.35). In conclusion, the location and degree of uterine cavity distortion are important factors that alter the normal development of a pregnancy and the birth rate. PMID:34765023 | PMC:PMC8576625 | DOI:10.3892/etm.2021.10917 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Perspectives on the diagnostic, predictive and prognostic markers of neuroendocrine neoplasms (Review)

xlomafota13 shared this article with you from Inoreader Perspectives on the diagnostic, predictive and prognostic markers of neuroendocrine neoplasms (Review) Via Experimental and therapeutic medicine Exp Ther Med. 2021 Dec;22(6):1479. doi: 10.3892/etm.2021.10914. Epub 2021 Oct 25. ABSTRACT Neuroendocrine neoplasms (NENs) are a heterogeneous group of rare tumors with different types of physiology and prognosis. Therefore, prognostic information, including morphological differentiation, grade, tumor stage and primary location, are invaluable and contribute to the formulation of treatment decisions. Biomarkers that are currently used, including chromogranin A (CgA), serotonin and neuron-specific enolase, are singular parameters that cannot be used to accurately predict variables associated with tumor growth, including proliferation, metabolic rate and metastatic potential. In addition, site-specific biomarkers, such as insulin and gastrin, cannot be applied to all types of NENs. The clinical application of broad-spectrum markers, as it is the case for CgA, remains controversial despite being widely used. Due to limitations of the curr ently available mono-analyte biomarkers, recent studies were conducted to explore novel parameters for NEN diagnosis, prognosis, therapy stratification and evaluation of treatment response. Identification of prognostic factors for predicting NEN outcome is a critical requirement for the planning of adequate clinical management. Advances in 'liquid' biopsies and genomic analysis techniques, including microRNA, circulating tumor DNA or circulating tumor cells and sophisticated biomathematical analysis techniques, such as NETest or molecular image-based biomarkers, are currently under investigation as potentially novel tools for the management of NENs in the future. Despite these recent findings yielding promising observations, further research is necessary. The present review therefore summarizes the existing knowledge and recent advancements in the exploration of biochemical markers for NENs, with focus on gastroenteropancreatic-neuroendocrine tumors. PMID:34765020 | PMC:PMC8576627 | DOI:10.3892/etm.2021.10914 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Environmental allergens house dust mite-induced asthma is associated with ferroptosis in the lungs

xlomafota13 shared this article with you from Inoreader Environmental allergens house dust mite-induced asthma is associated with ferroptosis in the lungs Via Experimental and therapeutic medicine Exp Ther Med. 2021 Dec;22(6):1483. doi: 10.3892/etm.2021.10918. Epub 2021 Oct 26. ABSTRACT Previous studies have indicated that allergens such as house dust mites (HDM) in the environment can induce allergic asthma. Ferroptosis is a newly discovered form of regulatory cell death characterized by aberrant lipid peroxidation and the accumulation of reactive oxygen species (ROS) in cells. However, whether ferroptosis participates in the pathological process of asthma remains to be elucidated. The present study used a HDM-induced mouse asthma model to determine the effect of HDM exposure on allergic asthma and its underlying mechanisms. Female BALB/c mice were intranasally exposed to HDM to induce allergic asthma. Airway hyperresponsiveness (AHR), lung inflammation, mucus secretion, IgE levels, cytokine levels and inflammatory cell counts in bronchoalveolar lavage fluid (BALF) were investigated. In addition, the morphological changes of mi tochondria, ROS levels, glutathione (GSH) levels and changes in ferroptosis pathway proteins were also determined in murine lungs. As a result, HDM exposure significantly increased AHR, inflammatory cell infiltration and mucus secretion around the airways. Furthermore, elevated IgE levels in the BALF, lung eosinophilia and a concomitant increase in IL-13 and IL-5 levels in BALF were observed. HDM inhalation increased ROS and decreased GSH levels in the lungs. HDM inhalation induced dysmorphic small mitochondria with decreased crista, as well as condensed, ruptured outer membranes. Western blotting demonstrated that the activities of glutathione peroxidase 4 and catalytic subunit solute carrier family 7 member 11 were significantly decreased, and that protein expression levels of acyl-CoA synthetase long-chain family member 4 and 15 lipoxygenase 1 were upregulated compared with mice in the normal control group. Overall, these results indicated that the AHR, airway inflammation, lipid peroxidation and ROS levels increased in HDM-induced asthma, and that HDM inhalation induced ferroptosis in the lungs, which helped to form an improved understanding of the pathogenesis of allergic asthma. PMID:34765024 | PMC:PMC8576623 | DOI:10.3892/etm.2021.10918 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Epigenetic approaches for cervical neoplasia screening (Review)

xlomafota13 shared this article with you from Inoreader Epigenetic approaches for cervical neoplasia screening (Review) Via Experimental and therapeutic medicine Exp Ther Med. 2021 Dec;22(6):1481. doi: 10.3892/etm.2021.10916. Epub 2021 Oct 25. ABSTRACT Human papillomavirus (HPV) infection is the leading cause of cervical cancer. The Papanicolaou cytology test is the usually employed type of screening for this infection; however, its sensibility is limited. Only a small percentage of women infected with high-risk HPV develop cervical cancer with an array of genetic and epigenetic modifications. Thus, it is necessary to develop rapid, reproducible and minimally invasive technologies for screening. DNA methylation has gained attention as an alternative method for molecular diagnosis and prognosis in HPV infection. The aim of the present review was to highlight the potential of DNA methylation in cervical neoplasia screening for clinical applications. It was observed that the methylation human and viral genes was correlated with high-grade lesions and cancer. Methylation biomarkers have shown a goo d capacity to discriminate between high-grade lesions with a transformative potential and cervical cancer, being able to detect these modifications at an early stage. With further research, the epigenetic profiles and subtypes of the tumors could be elaborated, which would aid in therapy selection by opening avenues in personalized precision medicine. Response to therapy could also be evaluated through such methods and the accessibility of liquid biopsies would allow a constant monitoring of the patient's status without invasive sampling techniques. PMID:34765022 | PMC:PMC8576616 | DOI:10.3892/etm.2021.10916 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Reduced miR-519d-3p levels in the synovium and synovial fluid facilitate the progression of post-traumatic osteoarthritis by targeting VEGF

xlomafota13 shared this article with you from Inoreader Reduced miR-519d-3p levels in the synovium and synovial fluid facilitate the progression of post-traumatic osteoarthritis by targeting VEGF Via Experimental and therapeutic medicine Exp Ther Med. 2021 Dec;22(6):1478. doi: 10.3892/etm.2021.10913. Epub 2021 Oct 25. ABSTRACT The present study aimed to investigate the expression and clinical significance of miR-519d-3p in patients with post-traumatic osteoarthritis (PTOA). The levels of miR-519d-3p in the synovium and synovial fluid (SF) of all subjects were detected by reverse transcription-quantitative polymerase chain reaction. The results of the present study demonstrated that the levels of miR-519d-3p in the synovium and SF of patients with PTOA were significantly lower, but that the VEGF content was significantly higher, compared with that of control group. Dual-luciferase reporter and Western blot assays demonstrated that VEGF was a target gene of miR-519d-3p. Furthermore, miR-519d-3p inhibitor-induced cell apoptosis, and cell cycle arrest could be partially reversed by silencing VEGF. Additionally, the level of miR-519d-3p in the synovium and SF of patients wi th PTOA was negatively correlated with the level of VEGF. ROC analysis demonstrated that miR-519d-3p levels in the synovium and SF could effectively differentiate patients with PTOA from healthy controls, with areas under the ROC curve of 0.928 and 0.896, respectively. In conclusion, reduction of miR-519d-3p in the synovium and SF resulted in the upregulation of VEGF in patients with PTOA, and miR-519d-3p may be a potential therapeutic target of PTOA. PMID:34765019 | PMC:PMC857 6619 | DOI:10.3892/etm.2021.10913 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Testicular injury during SARS-CoV-2 infection may be neglected: An assessment from scRNA-seq profiling and protein detection of angiotensin-converting enzyme II

xlomafota13 shared this article with you from Inoreader Testicular injury during SARS-CoV-2 infection may be neglected: An assessment from scRNA-seq profiling and protein detection of angiotensin-converting enzyme II Via Experimental and therapeutic medicine Exp Ther Med. 2021 Dec;22(6):1485. doi: 10.3892/etm.2021.10920. Epub 2021 Oct 26. ABSTRACT Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is outbreaking globally. SARS-CoV-2 invades host cells via angiotensin-converting enzyme II (ACE2) and causes multiple-organ injury. Autopsy studies indicated that the testis of patients with COVID-19 exhibited various degrees of spermatogenic cell reduction and injury, but the composition of ACE2-expressing cells and their proportion in the testes have remained to be determined. Recent clinical evidence suggested that the ratio of male sex hormones in males with COVID-19 was significantly changed. The present study aimed to explore whether SARS-CoV-2 is able to damage the male reproductive system. For this, the ACE2-expressing cell composition and proportion in male testes were analyzed using single-cell RNA sequencing (RNA-seq) datasets downloaded from the Gene Expression Omnibus (GEO) database and immunohistochemical (IHC) staining. The single-cell RNA-seq data indicated that ACE2 mRNA was highly expressed in myoid cells, Leydig cells and spermatogenic cells, accounting for 5.45, 1.24 and 0.423% of adult testicular cells. ACE2 mRNA-expressing Sertoli cells, spermatogenic cells and myoid cells accounted for 5.00, 0.56 and 0.73% of infant testicular cells. IHC demonstrated that ACE2 protein was also highly expressed in testicular tissues. In conclusion, the present results demonstrated that testicular injury may be missed by clinicians in patients with COVID-19 and male reproductive function should be closely followed up. PMID:34765026 | PMC:PMC8576622 | DOI:10.3892/etm.2021.10920 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Honokiol inhibits endoplasmic reticulum stress-associated lipopolysaccharide-induced inflammation and apoptosis in bovine endometrial epithelial cells

xlomafota13 shared this article with you from Inoreader Honokiol inhibits endoplasmic reticulum stress-associated lipopolysaccharide-induced inflammation and apoptosis in bovine endometrial epithelial cells Via Experimental and therapeutic medicine Exp Ther Med. 2021 Dec;22(6):1476. doi: 10.3892/etm.2021.10911. Epub 2021 Oct 22. ABSTRACT Honokiol (HKL) has been previously reported to exert anti-inflammatory effects in numerous diseases. However, the role of HKL in endometritis remains unclear. The present study aimed to explore and elucidate the role of HKL in a lipopolysaccharide (LPS)-induced in vitro model of endometritis. Bovine endometrial epithelial cells (bEECs) were pre-treated with HKL at doses of 1, 10 and 20 µM, followed by 1 µg/ml LPS. MTT assay was then used to detect cell viability. ELISA was utilized to measure the levels of the proinflammatory cytokines TNF-α, IL-1β and IL-6 in bEECs culture supernatants. Reverse transcription-quantitative PCR was further performed to examine the mRNA expression levels of these cytokines. Cell apoptosis was observed by TUNEL staining and the levels of Bcl-2, Bax, cleaved caspase 3 and cleaved caspase 9 were assayed by w estern blotting. Western blotting was also performed to detect the expression levels of endoplasmic reticulum (ER) stress-related proteins activating transcription factor 6, CCAAT-enhancer-binding protein homologous protein, inositol-requiring enzyme 1 and cleaved caspase 12 in bEECs. LPS treatment reduced cell viability and HKL treatment improved the viability of bEECs after LPS treatment. The LPS-induced inflammatory response and apoptosis in bEECs were also inhibited by HKL treatment. Additionally, the increased expression of ER stress-related proteins induced by LPS was reversed by HKL treatment. Following stimulation with the ER stress inducer tunicamycin, it was revealed that HKL attenuated ER stress and inhibited LPS-induced inflammatory response and apoptosis in bEECs. In summary, HKL inhibited ER stress associated with LPS-induced inflammation and apoptosis in bEECs, providing evidence that HKL can serve to be a novel agent for the treatment of endometritis. PMID:34765017 | PMC:PMC8576620 | DOI:10.3892/etm.2021.10911 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Effects of hydroxyapatite extract on rats with transient ischemia: Long-term potentiation and axon regeneration

xlomafota13 shared this article with you from Inoreader Effects of hydroxyapatite extract on rats with transient ischemia: Long-term potentiation and axon regeneration Via Experimental and therapeutic medicine Exp Ther Med. 2021 Dec;22(6):1486. doi: 10.3892/etm.2021.10921. Epub 2021 Oct 26. ABSTRACT Hydroxyapatite (HA) has been extensively used as a reconstructive and prosthetic material for osseous tissue. The present study aimed to determine whether HA extract exerted effects on central nervous system injury following transient cerebral ischemia/reperfusion in rats. Male Wistar rats were treated with HA following bilateral common carotid artery clamping (two-vessel occlusion). The results demonstrated that treatment with HA extract attenuated the inhibition of long-term potential in a rat model of transient cerebral ischemia/reperfusion. Furthermore, HA extract improved axon regeneration, which was confirmed via the immunohistochemical analysis of growth associated protein 43 and glial fibrillary acidic protein. Taken together, the results of the present study provided preliminary evidence of the protective effect of HA on neuronal damage. PMID:34765027 | PMC:PMC8576626 | DOI:10.3892/etm.2021.10921 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Heat-induced antigen retrieval in fluorescence in situ hybridization: An effective approach enhancing signal intensity in poor-quality FFPE sections

xlomafota13 shared this article with you from Inoreader Heat-induced antigen retrieval in fluorescence <em>in situ</em> hybridization: An effective approach enhancing signal intensity in poor-quality FFPE sections Via Experimental and therapeutic medicine Exp Ther Med. 2021 Dec;22(6):1480. doi: 10.3892/etm.2021.10915. Epub 2021 Oct 25. ABSTRACT Fluorescence in situ hybridization (FISH) serves as an ancillary tool for assessing chromosomal abnormalities and is important in differential diagnoses and treatment decisions. In clinical practice, pathologists encounter unsatisfactory formalin-fixed paraffin-embedded (FFPE) sections exhibiting weak fluorescence signals, mostly due to inappropriate tissue processing or preservation, leading to interpretation difficulties. For the present study, FFPE samples for which conventional FISH failed were collected. Instead of a pretreatment step using a commercial kit, heat-induced antigen retrieval (HIAR) was introduced using either citrate buffer or Tris-EDTA buffer, while the subsequent experimental workflow remained unchanged. After HIAR-assisted FISH, the hybridization efficiency and signal intensity were markedly enhanced and no difference in signal adequacy was observed when comparing the effect of the two AR solutions. The present study demonstrated that HIAR is a reliable tool for FISH, particularly for poor-quality FFPE sections yielding weak or no fluorescence signals in the conventional analysis. PMID:34765021 | PMC:PMC8576618 | DOI:10.3892/etm.2021.10915 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

LncRNA NR2F2-AS1 induces epithelial-mesenchymal transition of non-small cell lung cancer by modulating BVR/ATF-2 pathway via regulating miR-545-5p/c-Met axis

xlomafota13 shared this article with you from Inoreader LncRNA NR2F2-AS1 induces epithelial-mesenchymal transition of non-small cell lung cancer by modulating BVR/ATF-2 pathway via regulating miR-545-5p/c-Met axis Via American Journal of Cancer Research Am J Cancer Res. 2021 Oct 15;11(10):4844-4865. eCollection 2021. ABSTRACT Non-small cell lung cancer (NSCLC) is one type of the most common cancers, which results in the major death worldwide. This study focuses on the understanding of the molecular mechanism of lncRNA NR2F2-AS1 and its regulation on epithelial-mesenchymal transition (EMT) in the development of NSCLC. Expressions of lncRNA NR2F2-AS1, miR-545-5p, c-Met, biliverdin reductase (BVR), ATF-2 and EMT-related markers in NSCLC tissues and cells were measured by western blotting and RT-qPCR assays. The impact of lncRNA NR2F2-AS1 and miR-545-5p on the cell proliferation, migration, invasion and EMT were analyzed by CCK-8, colony formation, wound healing and transwell assays. The interactions among lncRNA NR2F2-AS1, miR-545-5p and c-Met predicted by bioinformatic analysis were evaluated through dual luciferase reporter assay and fluorescence in situ hybridization (FISH). After gen erating tumor xenografts, immunohistochemistry was utilized to measure the expression of Ki-67 and EMT-related proteins in vivo. Our results showed that lncRNA NR2F2-AS1, c-Met, BVR and ATF-2 were overexpressed while miR-545-5p was silenced in NSCLC tissues and cells. Silencing of lncRNA NR2F2-AS1 or upregulating miR-545-5p significantly inhibited the cell proliferation, migration, invasion and EMT process. The EMT process could be inhibited by suppressing c-Met/BVR/ATF-2 axis. The tumor xenograft experiments demonstrated that the tumor growth and EMT process were significantly inhibited by silencing lncRNA NR2F2-AS1 or overexpression of miR-545-5p in vivo. LncRNA NR2F2-AS1 promoted the NSCLC development through suppressing miR-545-5p to activate EMT process through c-Met/BVR/ATF-2 axis. Our study indicated that lncRNA NR2F2-AS1 and miR-545-5p could be used as potential therapeutic targets to improve NSCLC treatment. PMID:34765296 | PMC:PMC8569365 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.