Rapid screening of UPB1 gene variations by high resolution melting curve analysis

xlomafota13 shared this article with you from Inoreader Rapid screening of <em>UPB1</em> gene variations by high resolution melting curve analysis Via Experimental and therapeutic medicine Exp Ther Med. 2021 Apr;21(4):403. doi: 10.3892/etm.2021.9834. Epub 2021 Feb 25. ABSTRACT The present study aimed to analyze gene mutations in patients with β-ureidopropinoase deficiency and establish a rapid detection method for β-ureidopropinoase (UPB1) pathogenic variations by high resolution melting (HRM) analysis. DNA samples with known UPB1 mutations in three patients with β-ureidopropinoase deficiency were utilized to establish a rapid detection method for UPB1 pathogenic variations by HRM analysis. Further rapid screening was performed on two patients diagnosed with β-ureidopropinoase deficiency and 50 healthy control individuals. The results showed that all known UPB1 gene mutations can be analyzed by a specially designed HRM assay. Each mutation has specific HRM profiles which could be used in rapid screening. The HRM method could correctly identify all genetic mutations in two children with β- ureidopropinoase deficiency. In addition, the HRM assay also recognized four unknown mutations. To conclude, the results support future studies of applying HRM analysis as a diagnostic approach for β-ureidopropinoase deficiency and a rapid screening method for UPB1 mutation carriers. PMID:33692834 | PMC:PMC7938451 | DOI:10.3892/etm.2021.9834 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Calcium-binding and coiled-coil domain 2 promotes the proliferation and suppresses apoptosis of prostate cancer cells

xlomafota13 shared this article with you from Inoreader Calcium-binding and coiled-coil domain 2 promotes the proliferation and suppresses apoptosis of prostate cancer cells Via Experimental and therapeutic medicine Exp Ther Med. 2021 Apr;21(4):405. doi: 10.3892/etm.2021.9836. Epub 2021 Feb 25. ABSTRACT Prostate cancer (PCa) is considered to be one of the most common tumors in men. Calcium-binding and coiled-coil domain 2 (CALCOCO2) is a known important xenophagy receptor, which mediates intracellular bacterial degradation. To the best of the authors' knowledge, the present study is the first to demonstrate that CALCOCO2 functions as an oncogene in PCa. The results of the current study indicated that CALCOCO2 knockdown suppressed cell proliferation and colony formation, whereas it promoted apoptosis of PCa cells. In addition, knockdown of CALCOCO2 in PCa cells reduced cyclin-E1 and increased p53 protein expression. Bioinformatics analysis revealed that CALCOCO2 was associated with 'autophagosome assembly', 'nucleophagy' and 'nucleic acid metabolic process' biological processes and interacted with sequestosome-1, microtubule-associated proteins 1A/ 1B light chain 3 (MAP1LC3)B, γ-aminobutyric acid receptor-associated protein, IκB kinase subunit γ and MAP1LC3C. Moreover, CALCOCO2 protein levels were indicated to be significantly increased in PCa samples compared with normal prostate tissues. These results suggested that CALCOCO2 may be of value as a diagnostic and therapeutic target in PCa. PMID:33692836 | PMC:PMC7938445 | DOI:10.3892/etm.2021.9836 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Long non-coding RNA OIP5-AS1 contributes to cisplatin resistance of oral squamous cell carcinoma through the miR-27b-3p/TRIM14 axis

xlomafota13 shared this article with you from Inoreader Long non-coding RNA OIP5-AS1 contributes to cisplatin resistance of oral squamous cell carcinoma through the miR-27b-3p/TRIM14 axis Via Experimental and therapeutic medicine Exp Ther Med. 2021 Apr;21(4):408. doi: 10.3892/etm.2021.9839. Epub 2021 Feb 25. ABSTRACT Oral squamous cell carcinoma (OSCC) accounts for 90% of oral cavity cancer types, but the overall prognosis for patients with OSCC remains unfavorable. Cisplatin (DDP) is an effective drug in OSCC treatment, but DDP resistance weakens its therapeutic effect. Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) can trigger DDP resistance. The purpose of the current study was to explore the role and mechanism ofOIP5-AS1 in OSCC DDP resistance. In the present study, the expression levels of OIP5-AS1, microRNA (miR)-27b-3p and tripartite motif-containing 14 (TRIM14) were detected by reverse transcription-quantitative PCR. DDP resistance was measured using an MTT assay. Moreover, cell proliferation, migration and invasion were assessed by MTT, Transwell, and Matrigel assays. Protein expression levels of TRIM14, E-cadherin, N-cadherin and Vimentin were d etected by western blot analysis. Putative binding sites between miR-27b-3p andOIP5-AS1 or TRIM14werepredicted with starBase and verified using a dual-luciferase reporter assay. The role of OIP5-AS1 in DDP resistance of OSCC in vivo was measured using a xenograft tumor model. It was observed that OIP5-AS1 was upregulated in DDP-resistant OSCC cells, and the knockdown of OIP5-AS1 improved DDP sensitivity in DDP-resistant OSCC cells. The present study identified that miR-27b-3p was a target of OIP5-AS1. Furthermore, miR-27b-3p silencing reversed the effect of OIP5-AS1 knockdown on DDP sensitivity in DDP-resistant OSCC cells. TRIM14was shown to be a direct target of miR-27b-3p, and TRIM14 overexpression abolished the effect of miR-27b-3p on DDP sensitivity in DDP-resistant OSCC cells. The results suggested that OIP5-AS1 increased TRIM14 expression by sponging miR-27b-3p. In addition, OIP5-AS1 knockdown enhanced DDP sensitivity of OSCC in vivo. Data from the present study indicated that OIP5-AS1 may improve DDP resistance through theupregulationTRIM14 mediated bymiR-27b-3p, providing a possible therapeutic strategy for OSCC treatment. PMID:33692839 | PMC:PMC7938452 | DOI:10.3892/etm.2021.9839 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

MicroRNA-200b relieves LPS-induced inflammatory injury by targeting FUT4 in knee articular chondrocytes in vitro

xlomafota13 shared this article with you from Inoreader MicroRNA-200b relieves LPS-induced inflammatory injury by targeting FUT4 in knee articular chondrocytes <em>in vitro</em> Via Experimental and therapeutic medicine Exp Ther Med. 2021 Apr;21(4):407. doi: 10.3892/etm.2021.9838. Epub 2021 Feb 25. ABSTRACT Osteoarthritis (OA), characterized by the degeneration of articular cartilage, is a major problem in aging populations, and cartilage chondrocytes have been indicated to serve a curial role in the progression of OA. MicroRNA-200b-3p (miR-200b) was preliminarily identified to participate in OA. However, its role and mechanism of action in injured chondrocytes in OA remain unclear to date. In the present study, lipopolysaccharide (LPS)-treated cells isolated from normal knee articular cartilage were used to mimic inflammatory injury of OA chondrocytes. Cell viability, apoptosis and inflammatory responses were detected using Cell Counting Kit-8, flow cytometry and enzyme-linked immunosorbent assay, respectively. The expression levels of miR-200b and fucosyltransferase-4 (FUT4) were measured by reverse transcription-quantitative PCR and western blottin g. The association between miR-200b and FUT4 was verified using TargetScan software, dual-luciferase reporter assay and RNA immunoprecipitation. The results indicated that LPS treatment decreased cell viability of primary chondrocytes, and increased apoptosis rate and production of IL-1β, IL-6 and TNF-α. The expression level of miR-200b was downregulated, and that of FUT4 was upregulated in OA cartilage tissues and LPS-treated normal chondrocytes compared with normal cartilage tissues and chondrocytes. Overexpression of miR-200b via transfection with miR-200b mimic inhibited the apoptosis rate and reduced the levels of IL-1β, IL-6 and TNF-α in LPS-stimulated chondrocytes. However, the suppressive effect of miR-200b overexpression on the LPS-induced inflammatory injury in chondrocytes was reversed by the restoration of FUT4 levels. Notably, FUT4 was indicated to be a downstream target of miR-200b and was negatively regulated by miR-200b. Taken together, the results of the current study indicated that miR-200b protected chondrocytes from LPS-induced inflammatory injury in vitro by targeting FUT4. These findings revealed the miR-200b/FUT4 axis as a potential candidate to target the degeneration of cartilages, thereby inhibiting the progression of OA. PMID:33692838 | PMC:PMC7938448 | DOI:10.3892/e tm.2021.9838 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Allyl isothiocyanate increases MRP1 expression in cigarette smoke extract-stimulated human bronchial epithelial cells via the JNK/Nrf2 pathway

xlomafota13 shared this article with you from Inoreader Allyl isothiocyanate increases MRP1 expression in cigarette smoke extract-stimulated human bronchial epithelial cells via the JNK/Nrf2 pathway Via Experimental and therapeutic medicine Exp Ther Med. 2021 Apr;21(4):409. doi: 10.3892/etm.2021.9840. Epub 2021 Feb 25. ABSTRACT Multidrug resistance-related protein 1 (MRP1) is involved in the biological transport of several molecules with diverse structural characteristics outside of the cell. In addition to its transport activity, MRP1 exhibits multiple defense mechanisms in vivo. MRP1 is highly expressed in normal lung tissues and plays a protective role in the process of chronic obstructive pulmonary disease. In the present study, human bronchial epithelial cells (16HBE14o-cells) were stimulated by cigarette smoke extract (CSE) in vitro to simulate a smoking environment. On this basis, the mechanism of Allyl isothiocyanate (AITC) administration on the expression of MRP1 in CSE-stimulated 16HBE14o-cells was investigated. The effects of CSE on the viability of 16 HBE14o-cells were investigated by an MTT assay. The changes in the mRNA expression levels of nuc lear erythroid factor 2 (Nrf2) and MRP1 were investigated in CSE-stimulated 16HBE14o-cells using western blotting and reverse transcription quantitative PCR (RT-qPCR). Immunofluorescence analysis was used to detect Nrf2 nuclear translocation. Incubation of the cells with 5% CSE for 24 h had minor effects on cell viability and resulted in the activation of the JNK and p38MAPK signaling pathways. AITC activated the JNK pathway, inhibited the activation of the p38MAPK pathway in 16HBE14o-cells stimulated by 5% CSE and upregulated the expression levels of Nrf2 and MRP1 in a time-dependent manner. The upregulation of Nrf2, MRP1 and of Nrf2, and MRP1 mRNA expression levels in CSE-stimulated cells was inhibited by pretreatment with SP600125 (a JNK pathway inhibitor). Furthermore, the fluorescence intensity in the nucleus was significantly enhanced following AITC pretreatment and the analysis indicated nuclear translocation of Nrf2 in the cells. These results indicated that Nrf2 and MRP1 ex pression levels in CSE-stimulated cells were altered following AITC pretreatment. Thus demonstrating that the primary mechanism may be associated with activation of the JNK pathway, while the p38MAPK pathway may not be involved. PMID:33692840 | PMC:PMC7938453 | DOI:10.3892/etm.2021.9840 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Effects of dexmedetomidine on immune function, renal function and inflammatory factors of patients undergoing percutaneous nephrolithotomy under general anesthesia

xlomafota13 shared this article with you from Inoreader Effects of dexmedetomidine on immune function, renal function and inflammatory factors of patients undergoing percutaneous nephrolithotomy under general anesthesia Via Experimental and therapeutic medicine Exp Ther Med. 2021 Apr;21(4):406. doi: 10.3892/etm.2021.9837. Epub 2021 Feb 25. ABSTRACT The present study was designed to determine the effects of dexmedetomidine on immune function, renal function and inflammatory factors in patients undergoing percutaneous nephrolithotomy under general anesthesia. A total of 177 patients with kidney calculi who underwent percutaneous nephrolithotomy in The Second Affiliated Hospital of Fujian Medical University were enrolled, in which 91 patients were treated with dexmedetomidine during surgery (research group) and 86 patients were not sedated during surgery (control group). The vital signs, renal function, inflammatory factors and immune function during surgery between the two groups were compared. Patients in the research group showed improved vital signs, renal function, inflammatory factors and immune function compared with the control group (P<0.05), and also experienced a significantly shor ter hospitalization time (P<0.001). Therefore, the present results suggested that with a relatively high safety profile, use of dexmedetomidine for sedation can effectively protect renal and immune functions, and reduce the inflammatory response of patients during percutaneous nephrolithotomy. Thus, dexmedetomidine may have be potentially applied in clinical practice. PMID:33692837 | PMC:PMC7938444 | DOI:10.3892/etm.2021.9837 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Influence of periampullary diverticula on endoscopic retrograde cholangiopancreatography

xlomafota13 shared this article with you from Inoreader Influence of periampullary diverticula on endoscopic retrograde cholangiopancreatography Via Experimental and therapeutic medicine Exp Ther Med. 2021 Apr;21(4):410. doi: 10.3892/etm.2021.9841. Epub 2021 Feb 25. ABSTRACT The present study aimed to explore the influence of the presence of periampullary diverticula (PAD) on the implementation of endoscopic retrograde cholangiopancreatography (ERCP). A total of 388 patients with pancreaticobiliary disease who underwent ERCP for the first time between January 2017 and December 2018 were included and they were divided into a PAD group (n=179) and non-PAD (N-PAD) group (n=209) according to the presence or absence of PAD. A logistic regression model was used to analyze the risk factors for PAD. The prevalence of PAD in males was higher than that in females [odds ratio (OR)=2.250, 95% CI: 1.670-3.801]. The prevalence of PAD in patients with bile duct stone was 57.92% and higher than that in patients without stone (OR=4.475, 95% CI: 2.932-7.679). The morbidity of PAD in elderly patients with bile duct stone was higher than in those without stone (OR=6.728, 95% CI: 3.790-11.943). Among the elderly patients, the constituent ratio of males in the PAD group was higher than that in the N-PAD group (χ2=13.543, P<0.001). The constituent ratio of patients who underwent endoscopic sphincterotomy (EST) was lower than that in the N-PAD group (χ2=10.800, P<0.001). In conclusion, the occurrence of PAD was high in elderly males and closely related to the occurrence of bile duct stones. PMID:33692841 | PMC:PMC7938449 | DOI:10.3892/etm.2021.9841 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Systemic mastocytosis with flushing and hypotension: A case report and literature review

xlomafota13 shared this article with you from Inoreader Systemic mastocytosis with flushing and hypotension: A case report and literature review Via Experimental and therapeutic medicine Exp Ther Med. 2021 Apr;21(4):404. doi: 10.3892/etm.2021.9835. Epub 2021 Feb 25. ABSTRACT Systemic mastocytosis (SM) is a heterogeneous disease of the bone marrow, which is characterized by the abnormal proliferation and infiltration of mast cells in one or more organs, such as the skin, bone marrow, digestive tract, liver and spleen. Urticaria pigmentosa is a typical but infrequent manifestation of SM. Other clinical presentations are non-specific, varying from pruritus and hypotension to multiple organ dysfunction, which may be lethal when hemodynamic changes occur, such as the sharp decline in blood pressure observed in the present case. In patients who lack skin lesions, the diagnosis of SM is frequently challenging. The present study reported on a 58-year-old male who presented with episodic flushing and syncope. The patient demonstrated marked neutrophilia and reduced blood potassium concentrations soon after the onset of each epi sode, which was able to last several hours, ranging from once to four times a year. SM without skin lesions was suspected and confirmed after multifocal bone marrow aspiration, which revealed dense infiltrates of mast cells (≥15 mast cells), with positive toluidine blue and CD117 staining. The present case illustrates the significance of taking SM or mast cell activation syndrome into consideration when unexplained recurrent hypotension or even syncope are observed, care should be taken to exclude differential diagnoses, as some of them may have much poorer prognoses and require alternative treatments. PMID:33692835 | PMC:PMC7938450 | DOI:10.3892/etm.2021.9835 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Two birds with one stone.–Addressing depressive symptoms, emotional tension and worry improves tinnitus-related distress and affective pain perceptions in patients with chronic tinnitus

xlomafota13 shared this article with you from Inoreader Two birds with one stone.–Addressing depressive symptoms, emotional tension and worry improves tinnitus-related distress and affective pain perceptions in patients with chronic tinnitus Via Tinnitus by Benjamin Boecking, Matthias Rose, Petra Brueggemann, Birgit Mazurek Background Psychological factors link the co-occurrence of tinnitus-related distress and pain perceptions in patients with chronic tinnitus. Objective This study examines, if treatment-related changes in these factors ameliorate both tinnitus-related distress and pain perceptions in a sample of patients with chronic tinnitus. Methods N = 1238 patients with chronic tinnitus provided pre- and post-treatment ratings of tinnitus-related distress and affective or sensory pain perceptions alongside measures of depressive symptoms and perceived stress. Treatment comprised an intensive tinnitus-specific multimodal treatment program. Using serial indirect-effects analyses, we examined association patterns between baseline values and change rates of those variables that were found to respond to treatment. Results Small effect sizes emerged for changes in tinnitus-related distress, affective (but not sensory) pain perceptions, depressive symptoms, emotional tensio n and worry. At pre- or post-treatment respectively, baseline values and change rates intercorrelated. Across timepoints, (1) baseline tinnitus-related distress and affective pain perceptions were positively associated with improvements in tinnitus-related distress, affective pain perceptions and depressive symptoms. (2) Baseline depressive symptoms or emotional tension mediated positive associations between baseline tinnitus-related distress and improvement in affective pain perceptions. (3) Change in depressive symptoms mediated the effect of baseline tinnitus-related distress on change in affective pain perceptions–partly through associated change in emotional tension or worry. Mood-independent aspects of emotional tension were negatively associated with improvement in affective pain perceptions. Conclusions Depressive symptoms, emotional tension and worry emerge as key predictors of treatment response and transdiagnostic treatment targets for alleviating tinnitus-related distress and functionally associated affective pain perceptions. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Tinnitus treatment by vagus nerve stimulation: A systematic review

xlomafota13 shared this article with you from Inoreader Tinnitus treatment by vagus nerve stimulation: A systematic review Via Tinnitus by I. Stegeman, H. M. Velde, P. A. J. T. Robe, R. J. Stokroos, A. L. Smit Background Tinnitus is a phantom sensation of sound, which can have a negative impact on quality of life of those affected. No curative treatments are currently known. Neuromodulation by vagus nerve stimulation has emerged as a new treatment option for tinnitus, though till date the effectiveness remains unclear. Therefore, we aim to review the effect of vagus nerve stimulation on tinnitus distress and tinnitus symptom severity in patients with chronic tinnitus. Methods We searched Pubmed, Embase and the Cochrane Library systematically for RCTs, observational studies and case studies on the effect of VNS treatment for tinnitus on October 29, 2019. Studies including adult patients with subjective tinnitus, comparing transcutaneous or implantable VNS to placebo or no treatment or before and after application of VNS treatment on tinnitus distress and tinnitus symptom severity measured with a validated questionnaire were eligible. The risk of bias was assessed with the appropri ate tool for each type of study. Results Our search identified 9 primary studies of which 2 RCTs, 5 cohort studies and 2 case series or reports. 5 studies used transcutaneous VNS treatment and 4 used implanted VNS treatment. 6 studies combined VNS treatment with sound therapy. There was a serious risk of bias in all studies, especially on confounding. Most studies reported a small decrease in tinnitus distress or tinnitus symptom severity. Conclusion Due to methodological limitations and low reporting quality of the included studies, the effect of VNS on tinnitus remains unclear. To draw conclusions for which patient population and to what extent (t)VNS is beneficial in the treatment of tinnitus, a randomised controlled trial should be considered. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.