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Review Exp Ther Med
2021 Jan;21(1):24. doi: 10.3892/etm.2020.9456. Epub 2020 Nov 9.
Interleukin-6 signaling blockade treatment for cytokine release syndrome in COVID-19 (Review)
Jia-Jie Chen 1, Li-Na Zhang 1, Hu Hou 2, Lingqing Xu 3, Kunmei Ji 1
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PMID: 33262810 PMCID: PMC7690237 DOI: 10.3892/etm.2020.9456
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Abstract
A severe immune response in patients with coronavirus disease 2019 (COVID-19) can cause a potentially lethal unconstrained inflammatory cytokine storm, known as cytokine release syndrome (CRS). The present study provides an overview of the biology underlying CRS and how targeted inhibition of interleukin (IL)-6 signaling may improve outcomes and the survival of patients suffering from COVID-19. Preliminary clinical results have indicated that antagonism of the IL-6 receptor (IL-6R), including with the FDA-approved humanized monoclonal antibody tocilizumab, can improve the outcomes of patients with severe or critical COVID-19 while maintaining a good safety profile. The available clinical data support the expansion of clinical trials using IL-6R targeting inhibitors for severe and critical COVID-19 treatment.
Keywords: Tocilizumab; clinical trials; coronavirus disease 2019; cytokine release syndrome; interleukin-6 signaling.
Copyright: © Chen et al.
39 references1 figure
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Review Exp Ther Med
2021 Jan;21(1):33. doi: 10.3892/etm.2020.9465. Epub 2020 Nov 11.
Towards a more effective strategy for COVID-19 prevention (Review)
Anna K Szkaradkiewicz-Karpińska 1, Andrzej Szkaradkiewicz 2
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PMID: 33262819 PMCID: PMC7690340 DOI: 10.3892/etm.2020.9465
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Abstract
At the end of 2019, a new disease, similar to severe acute respiratory syndrome (SARS) associated with SARS-CoV was reported in Wuhan, China. It was quickly discovered that the etiological factor of the new disease (COVID-19) was a previously unknown SARS coronavirus 2 (SARS-CoV-2). The global spread of of COVID-19 has lead to the declaration of a pandemic status in 2019-2020 as declared by the World Health Organization and Public Health Emergency of International Concern. SARS-CoV-2 characterizes with high epidemic potential and is effectively disseminated between humans. SARS-CoV and SARS-CoV-2 are closely related pathogens. Their prime route of distribution is air-droplet transmission. Combating infectious diseases disseminated by inhalation is very difficult, and mainly relies on the use of vaccines. However, despite the lack of an effective anti-SARS-CoV vaccine and specific antiviral drugs, the strict sanitary procedures proved to be sufficient to stop the SARS epidemic in June 2003. However, epidemic research has indicated that SARS-CoV-2 is transmitted in humans significantly more effectively than SARS-CoV; therefore, the COVID-19 pandemic continues to expand. This indicates that the so far anti-epidemic activities to control COVID-19 are insufficient. In the current review, the possibility of using interferon α (IFN-α) as a preventive agent of COVID-19 is discussed. The current data concerning anti-COVID-19 vaccines and specific drugs against SARS-CoV-2 are also discussed. The aim of the current review is to contribute to the introduction of a more efficient strategy in the protection of the human population against COVID-19.
Keywords: COVID-19; SARS coronavirus 2; antivirals drugs; immunity; interferon; pandemic; public health; vaccines.
Copyright: © Szkaradkiewicz-Karpińska et al.
70 references
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3
Review Exp Ther Med
2021 Jan;21(1):35. doi: 10.3892/etm.2020.9467. Epub 2020 Nov 11.
Investigational drugs with dual activity against HBV and HIV (Review)
Shiyu Sun 1 2 3 4, Qing Yang 1 2 3 4, Yunjian Sheng 1 2 3 4, Yi Fu 4 5, Changfeng Sun 1 2 3 4, Cunliang Deng 1 2 3
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PMID: 33262821 PMCID: PMC7690342 DOI: 10.3892/etm.2020.9467
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Abstract
Chronic hepatitis B (CHB) and acquired immunodeficiency syndrome (AIDS) are global public health problems that pose a significant health burden. Human immunodeficiency virus (HIV) and hepatitis B virus (HBV) coinfection is common, as these viruses have similar transmission routes, such as blood transmission, sexual transmission and mother-to-child transmission. Coinfection frequently leads to accelerated disease progression. For individuals coinfected with HIV/HBV, combination antiretroviral therapy containing dual anti-HBV drugs is recommended. Certain studies have also indicated the benefits of antiretroviral drugs with anti-HBV activity in patients with coinfection. A total of four Food and Drug Administration-approved HIV drugs also have anti-HBV activity; namely, emtricitabine, lamivudine, tenofovir disoproxil fumarate and tenofovir alafenamide, which are all nucleoside reverse transcriptase inhibitors. However, various issues, including drug resistance and side effects, limit t heir application. Therefore, it is necessary to develop more drugs with dual activity against HBV and HIV. The present review outlines the mechanisms, safety and efficacy of certain drugs that have been investigated for this purpose.
Keywords: HIV; antiviral; coinfection; dual activity drug; hepatitis B virus; review.
Copyright: © Sun et al.
134 references
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Review Exp Ther Med
2021 Jan;21(1):44. doi: 10.3892/etm.2020.9475. Epub 2020 Nov 17.
Roles and regulatory mechanisms of miR-30b in cancer, cardiovascular disease, and metabolic disorders (Review)
Qing Zhang 1, Shousheng Liu 2 3, Jie Zhang 1, Xuefeng Ma 1, Mengzhen Dong 1, Baokai Sun 1, Yongning Xin 1 3 4
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PMID: 33273973 PMCID: PMC7706387 DOI: 10.3892/etm.2020.9475
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Abstract
MicroRNAs (miRNAs) are non-coding RNAs 21-23 nucleotides in length that regulate gene expression, and thereby modulate signaling pathways and protein synthesis in both physiological and pathogenic processes. miR-30b inhibits cell proliferation, migration, invasion and epithelial-mesenchymal transformation in multiple types of cancer. In addition to its role in several types of neoplasias, miR-30b has been shown to exhibit essential roles in cardiovascular and metabolic diseases. In the present review, an overview of the biological functions of miR-30b and its role in the pathogenesis of neoplastic, cardiovascular and metabolic diseases is provided. miR-30b is a potential candidate for clinical development as a diagnostic and prognostic biomarker, therapeutic agent and drug target. However, further research is required to elucidate its role in health and disease and to harness its potential clinical utility.
Keywords: biomarker; cardiovascular diseases; metabolism; miRNA-30b; tumor.
Copyright: © Zhang et al.
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5
Exp Ther Med
2021 Jan;21(1):48. doi: 10.3892/etm.2020.9479. Epub 2020 Nov 18.
Identification of adhesion-associated DNA methylation patterns in the peripheral nervous system
Shanhuai Zuo 1, Guidong Shi 2 3, Jianchao Fan 2 3, Baoyou Fan 2 3, Xiaolei Zhang 2 3, Shen Liu 2 3, Yan Hao 2 3, Zhijian Wei 2 3, Xianhu Zhou 2 3, Shiqing Feng 2 3
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PMID: 33273976 PMCID: PMC7706384 DOI: 10.3892/etm.2020.9479
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Abstract
Schwann cells are unique glial cells in the peripheral nervous system. These cells provide a range of cytokines and nutritional factors to maintain axons and support axonal regeneration. However, little is known concerning adhesion-associated epigenetic changes that occur in Schwann cells after peripheral nerve injury (PNI). In the present study, adhesion-associated DNA methylation biomarkers were assessed between normal and injury peripheral nerve. Specifically, normal Schwann cells (NSCs) and activated Schwann cells (ASCs) were obtained from adult Wistar rats. After the Schwann cells were identified, proliferation and adhesion assays were used to assess differences between NSCs and ASCs. Methylated DNA immunoprecipitation-sequencing and bioinformatics analysis were used to identify and analyze the differentially methylated genes. Reverse transcription-quantitative PCR was performed to assess the expression levels of adhesion-associated genes. In the present study, the proliferation and adhesion assays demonstrated that ASCs had a more robust proliferative activity and adhesion compared with NSCs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to identify methylation-associated biological processes and signaling pathways. Protein-protein interaction network analysis revealed that Fyn, Efna1, Jak2, Vav3, Flt4, Epha7, Crk, Kitlg, Ctnnb1 and Ptpn11 were potential markers for Schwann cell adhesion. The expression levels of several adhesion-associated genes, such as vinculin, BCAR1 scaffold protein, collagen type XVIII α1 chain and integrin subunit β6, in ASCs were altered compared with those in NSCs. The current study analyzed adhesion-associated DNA methylation patterns of Schwann cells and identified candidate genes that may potentially regulate Schwann cell adhesion in Wistar rats before and after PNI.
Keywords: DNA methylation; Gene Ontology; Kyoto Encyclopedia of Genes and Genomes; Schwann cells; bioinformatics; cell adhesion; nerve regeneration; peripheral nerve injuries; protein-protein interaction network.
Copyright: © Zuo et al.
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Exp Ther Med
2021 Jan;21(1):25. doi: 10.3892/etm.2020.9457. Epub 2020 Nov 9.
Fisetin ameliorates atherosclerosis by regulating PCSK9 and LOX-1 in apoE -/- mice
Li Yan 1, Qingling Jia 1, Hui Cao 1, Chuan Chen 1, Sanli Xing 1, Yan Huang 1, Dingzhu Shen 1
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PMID: 33262811 PMCID: PMC7690243 DOI: 10.3892/etm.2020.9457
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Abstract
The purpose of the current study was to investigate the mechanism by which fisetin improves atherosclerosis (AS) by regulating lipid metabolism and senescence in apolipoprotein E-deficient (apoE-/-) mice. An AS model was established by feeding apoE-/- mice a high-fat diet. Mice were randomly divided into the model group (n=18), the fisetin group (n=18) and the atorvastatin group (n=18). The control group (n=18) was composed of wild-type C57BL/6 mice of the same age and genetic background. The fisetin and atorvastatin groups were respectively treated with aqueous solutions of fisetin (12.5 mg/kg) and atorvastatin (2 mg/kg) via oral gavage daily for 12 weeks. The pathological morphology, lipid accumulation, collagen deposition of the aortic sinus were observed, serum lipids, superoxide dismutase (SOD) and malondialdehyde (MDA) levels and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were measured in the peripheral blood serum. Additionally, the expressi ons of proprotein convertase subtilisin/kexin type 9 (PCSK9), lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), tumor suppressor protein p53 (p53), cyclin-dependent kinase inhibitor 1A (p21) and multiple tumor suppressor-1 (p16) were analyzed in the aorta. The results of the current study indicated that compared with the control group, a large area of AS plaque in the aortic sinus that contained a large amount of red-stained lipids and decreased collagen fiber content were found in the model group, which exhibited higher total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), oxidized low-density lipoprotein (ox-LDL) and MDA levels; higher ALT and AST activities, lower high-density lipoprotein cholesterol (HDL-C) and SOD levels and increased expression levels of PCSK9, LOX-1, p53, p21 and p16. Fisetin is a phytochemical and bioflavonoid that serves a potential role in chronic diseases including AS, obesit y, diabetes and cancer due to its wide biological activities, such as regulating lipid metabolism and anti-aging, anti-oxidation and anti-inflammatory. Atorvastatin is recognized as a first-line treatment drug for AS; therefore it was used as a positive control in the current study. Following fisetin and atorvastatin treatment, both the AS plaque and the lipid accumulation in the aortic sinus were significantly reduced, and the expressions of PCSK9, LOX-1 and aging markers, including p53, p21 and p16 were downregulated.
Keywords: atherosclerosis; fisetin; lectin-like oxidized low-density lipoprotein receptor-1; lipid metabolism; proprotein convertase subtilisin/kexin type 9.
Copyright: © Yan et al.
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7
Exp Ther Med
2021 Jan;21(1):36. doi: 10.3892/etm.2020.9468. Epub 2020 Nov 11.
MicroRNA-219-5p participates in cyanotic congenital heart disease progression by regulating cardiomyocyte apoptosis
Chuanxian Hu 1, Su Huang 1, Fafu Wu 1, Hui Ding 1
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PMID: 33262822 PMCID: PMC7690344 DOI: 10.3892/etm.2020.9468
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Abstract
MicroRNAs (miRs) play important roles in the protection against and development of congenital heart disease (CHD). However, the role and potential mechanisms of miR-219-5p in cyanotic CHD remains unclear. Reverse transcription-quantitative PCR (RT-qPCR) was used to measure miR-219-5p levels in cyanotic CHD and hypoxia-induced H9C2 cells. Dual luciferase reporter gene assay was used to confirm whether liver receptor homolog-1 (LRH-1) was a direct target of miR-219-5p. miR-219-5p inhibitor and LRH-1-small interfering RNA were transfected into H9C2 cells under hypoxic conditions to investigate the role of miR-219-5p in hypoxia-induced H9C2 cells. Subsequently, cell viability was detected using an MTT assay and cell apoptosis was detected using flow cytometry. In addition, RT-qPCR and western blotting assays were performed to detect the mRNA and protein expression of LRH-1, cyclin D1 and β-catenin, respectively. The data showed that miR-219-5p expression was higher in patients with cyan otic CHD compared with patients with acyanotic CHD gradually increased in H9C2 cells with prolonged hypoxia time. Dual luciferase reporter assay results showed that LRH-1 was a direct target gene of miR-219-5p. Inhibition of miR-219-5p reversed hypoxia-induced cell viability reduction and attenuated hypoxia-induced cell apoptosis. In addition, hypoxia induction inhibited the expression of LRH-1, cyclin D1 and β-catenin, which was reversed by miR-219-5p inhibitor. However, LRH-1 downregulation reversed the miR-219-5p inhibitor enhanced cell viability, decreased cell apoptosis and increased expression of LRH-1, cyclin D1 and β-catenin in hypoxia-treated cardiomyocytes. The present results demonstrated that downregulation of miR-219-5p promoted the expression of the LRH-1/Wnt/β-catenin signaling pathway-associated components, reduced cardiomyocyte apoptosis and increased cell growth under hypoxic conditions. miR-219-5p may be a potential therapeutic target for cyanotic CHD therapy.< br />
Keywords: apoptosis; congenital heart disease; liver receptor homolog-1/Wnt/β-catenin signaling pathway; microRNA-219-5p.
Copyright: © Hu et al.
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8
Exp Ther Med
2021 Jan;21(1):28. doi: 10.3892/etm.2020.9460. Epub 2020 Nov 10.
Shikonin reduces hepatic fibrosis by inducing apoptosis and inhibiting autophagy via the platelet-activating factor-mitogen-activated protein kinase axis
Min Song 1, Heng Zhang 1, Zhitao Chen 1, Jing Yang 1, Jie Li 1, Sue Shao 1, Jing Liu 1
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PMID: 33262814 PMCID: PMC7690239 DOI: 10.3892/etm.2020.9460
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Abstract
Liver fibrosis is a tissue repair process that occurs following various types of chronic liver injury and can develop into liver cirrhosis, portal hypertension or liver cancer without effective treatment. Shikonin has anti-inflammatory, antiviral and antitumor properties. Furthermore, shikonin has an additional effect of antagonizing tissue and organ fibrosis. The aim of the present study was to evaluate the mechanisms of action underlying shikonin against liver fibrosis. Cell viability was assessed using the Cell Counting Kit-8 and EdU incorporation assays. Protein and mRNA expression levels were measured via western blotting and immunofluorescence assays, respectively. Apoptosis was examined via flow cytometry and autophagy via transmission electron microscopy. Compared with the control group, shikonin did not significantly alter LX-2 cell viability at 0.2 µmol/ml, which was used as the intervention concentration. However, shikonin significantly inhibited fibrosis, as indicated by a decrease in the expression of α-smooth muscle actin and collagen-I in the TGF-β + shikonin group compared with the TGF-β group. The results indicated that shikonin potentially inhibited fibrosis via promoting cell apoptosis and inhibiting autophagy. Additionally, the results of the present study indicated that shikonin downregulated the expression levels of platelet-activating factor (PAF) in TGF-β-treated cells, which subsequently activated the MAPK signaling pathway, leading to enhanced cell apoptosis and reduced autophagy. Collectively, the present study indicated that shikonin promoted cell apoptosis and suppressed autophagy via the PAF-MAPK axis in LX-2 cells, thus blocking the development of fibrosis. The results of the present study may provide a potential therapeutic strategy for liver fibrosis.
Keywords: autophagy; cell apoptosis; liver fibrosis; platelet-activating factor-MAPK signaling pathway.
Copyright © 2020, Spandidos Publications.
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9
Exp Ther Med
2021 Jan;21(1):52. doi: 10.3892/etm.2020.9484. Epub 2020 Nov 19.
Klotho gene improves oxidative stress injury after myocardial infarction
Zhuofan Xu 1, Shaoxin Zheng 2, Xiaoqian Feng 1, Chengzhe Cai 1, Xianqu Ye 1, Pingfang Liu 1
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PMID: 33273980 PMCID: PMC7706392 DOI: 10.3892/etm.2020.9484
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Abstract
The aim of the present study was to investigate the effects and mechanisms of the Klotho gene in oxidative stress injury after myocardial infarction. Sprague-Dawley rats were divided into five groups (sham, model, pDC316, LY294002, and pDC316-Klotho). Subsequently, the superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) concentrations were measured in myocardial tissues. Additionally, pathological differences among the groups were evaluated using hematoxylin and eosin and Masson's trichrome staining. Apoptosis was assayed by terminal deoxynucleotidyl transferase 2'-deoxyuridine-5'-triphosphate nick end-labeling assay, evaluated Klotho protein expression by immunohistochemical assay, and assessed Nrf 2 and ARE protein expressions using western blotting assay. As compared with in the sham group, the SOD, MDA, and GSH concentrations were significantly deteriorated (P<0.001, respectively); cardiomyocyte apoptosis index values were significantly increased (P<0.001); K lotho protein expression was significantly depressed; and Nrf-2 and ARE protein expressions were significantly (P<0.001, respectively) in the model and pDC316 groups. However, with Klotho supplementation by pDC316 transfection, as compared with in the model group, the SOD, MDA, and GSH concentrations were significantly improved (P<0.001, respectively); the cardiomyocyte apoptosis index values were significantly suppressed (P<0.001); and the pathology was improved. Further, the Klotho protein expression of the pDC316-Klotho group was significantly upregulated and the Nrf-2 and ARE proteins expressions of the LY294002 and pDC316-Klotho groups were significantly suppressed. Klotho overexpression improved findings of oxidative stress injury after myocardial infarction.
Keywords: ARE; Klotho; Nrf-2; myocardial infarction; oxidative stress.
Copyright: © Xu et al.
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10
Exp Ther Med
2021 Jan;21(1):23. doi: 10.3892/etm.2020.9455. Epub 2020 Nov 9.
Exposure to radiofrequency radiation increases the risk of breast cancer: A systematic review and meta-analysis
Ya-Wen Shih 1, Anthony Paul O'Brien 2, Chin-Sheng Hung 3 4, Kee-Hsin Chen 5 6 7 8, Wen-Hsuan Hou 8 9 10 11, Hsiu-Ting Tsai 1 5
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PMID: 33262809 PMCID: PMC7690245 DOI: 10.3892/etm.2020.9455
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Abstract
The present systematic review and meta-analysis investigated the association between exposure to radiofrequency radiation and the risk of breast cancer. The published studies that were available in PubMed, Embase, Cochrane Library, Ovid MEDLINE, CINAHL Plus, Web of Science, Airiti Library, Networked Digital Library of Theses and Dissertations and ProQuest until May 2020 were investigated. A total of eight studies (four case-control and four cohort studies) were eligible for quantitative analysis. A significant association between radiofrequency radiation exposure and breast cancer risk was detected [pooled relative risk (RR)=1.189; 95% confidence interval (CI), 1.056-1.339]. Subgroup analyses indicated that radiofrequency radiation exposure significantly increased the risk of breast cancer susceptibility among subjects aged ≥50 years (RR=2.179; 95% CI, 1.260-3.770). Pooled estimates revealed that the use of electrical appliances, which emit radiofrequency radiation, such as mobile phones and computers, significantly increased breast cancer development (RR=2.057; 95% CI, 1.272-3.327), while occupational radiofrequency exposure and transmitters did not increase breast cancer development (RR=1.274; 95% CI, 0.956-1.697; RR=1.133; 95% CI, 0.987-1.300, respectively). It was concluded that radiofrequency radiation exposure significantly increased the risk of breast cancer, especially in women aged ≥50 years and in individuals who used electric appliances, such as mobile phones and computers. In accordance with Preferred Reporting Items for Systematic Reviews and Meta-analysis, an evaluation protocol was prepared and registered with the PROSPERO database (registration no. CRD42018087283).
Keywords: breast cancer; meta-analysis; radiofrequency radiation; systematic review.
Copyright: © Shih et al.
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11
Exp Ther Med
2021 Jan;21(1):27. doi: 10.3892/etm.2020.9459. Epub 2020 Nov 9.
Investigation of the relationship between chronic montelukast treatment, asthma and depression-like behavior in mice
Banu Cahide Tel 1, Gokcen Telli 1, Sevgen Onder 2, Emirhan Nemutlu 3, Turgut Emrah Bozkurt 1
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PMID: 33262813 PMCID: PMC7690246 DOI: 10.3892/etm.2020.9459
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Abstract
In 2008, the Food and Drug Administration of the US issued a warning about the neuropsychiatric side effects of montelukast. Previous clinical studies on montelukast have reported conflicting results and, to the best of our knowledge, no experimental studies concerning these side effects had been conducted. In the current study, the effect of montelukast on depression-like behavior in an ovalbumin (OVA)-induced mouse model was investigated. A total of 3 OVA challenges were applied at 2 week intervals for the persistence of asthma. Depression-like behavior was assessed using forced swim tests following each challenge and locomotor activities were evaluated using open field tests. At the end of the current study, plasma montelukast concentrations were measured and the development of asthma and effect of montelukast treatment were histopathologically examined. Inflammation scores that were increased in the OVA mice following all challenges were indicated to be reduced by montelukast tre atment. The immobility time of mice increased beginning with the first challenge and this was also reduced by montelukast treatment. Montelukast administration to the control mice did not alter immobility times. Moreover, motor activity of the OVA and montelukast-treated mice were not altered. The results indicated there was no association between chronic montelukast treatment and depression. Furthermore, the chronic administration of montelukast to non-asthmatic mice did not increase immobility. However, depressive behavior increased at all time points in the OVA mice. These results indicated that chronic montelukast treatment is not associated with depression-like behavior and confirmed the association between asthma and depression. Further studies are required to provide an improved understanding of the neuropsychiatric side effects of montelukast.
Keywords: asthma; depression; forced swim test; montelukast; neuropsychiatric side-effects; ovalbumin.
Copyright: © Tel et al.
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12
Exp Ther Med
2021 Jan;21(1):55. doi: 10.3892/etm.2020.9487. Epub 2020 Nov 19.
Clinical efficacy of duodenoscopy combined with laparoscopy in the treatment of patients with severe acute pancreatitis and pancreatic pseudocyst, and the effects on IL-6 and CRP
Lianhua Zheng 1, Shasha Huang 2, Fengji Liu 3, Juan Yang 3
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PMID: 33273983 PMCID: PMC7706390 DOI: 10.3892/etm.2020.9487
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Abstract
The study aimed to investigate the clinical efficacy of duodenoscopy combined with laparoscopy in the treatment of patients with severe acute pancreatitis (SAP) and pancreatic pseudocyst (PP), and its effects on serum inflammatory factors. Altogether 94 patients complicated with SAP and PP who were admitted to Weifang People's Hospital (Weifang, China) from September 2015 to December 2018 were included. Based on the different operation methods, 49 patients who underwent traditional laparotomy under laparoscopic surgery were included in group A, and 45 patients who underwent duodenoscopy and laparoscopy under duodenoscope to treat the drainage of nipple and pancreatic pseudocysts were included in group B. The expression levels of related serum indexes and serum stress indexes before and at 48 h after surgery, the postoperative nausea, vomiting and abdominal pain scores, as well as the clinical efficacy, perioperative related indexes, recovery and complications were compared between th e two groups. The prognostic factors in both groups were assessed via Logistic univariate and multivariate analyses. C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-β (IL-β), endotoxin and nuclear factor κB (NF-κB) were significantly lower in group B than those in group A (P<0.001). Upregulating cortisol and norepinephrine in group B was lower than that in group A (P<0.001). The total effective rate in group B was higher than that in group A (P<0.05). The perioperative related indexes, recovery, and postoperative complications in group B were better than those in group A (P<0.05). Scores of abdominal pain, nausea and vomiting in group B were markedly lower than those in group A (P<0.001). Multivariate Logistic regression analysis showed that CRP, TNF-α, IL-6, IL-β and surgical methods were independent risk factors for the prognosis of patients with SAP and PP. In conclusion, the combined treatment with duodenoscopy and laparoscopi c surgery has little inflammatory and stress reaction, and it is highly safe, worthy to be popularized.
Keywords: CRP; IL-6; TNF-α; duodenoscopy; laparoscopy; severe acute pancreatitis complicated with pancreatic pseudocyst.
Copyright © 2020, Spandidos Publications.
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13
Exp Ther Med
2021 Jan;21(1):47. doi: 10.3892/etm.2020.9478. Epub 2020 Nov 18.
Effects of various catheter fix sites on catheter-associated lower urinary tract symptoms
Likun Zhu 1 2, Rui Jiang 1 2, Xiangjun Kong 1 2, Xinwei Wang 1 2, Lijun Pei 1 2, Qingfu Deng 1 2, Xu Li 1 2
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PMID: 33273975 PMCID: PMC7706396 DOI: 10.3892/etm.2020.9478
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Abstract
The present study aimed to compare the effects of various catheter fix sites on catheter-associated lower urinary tract symptoms (CALUTS) in 450 patients who underwent surgical removal of upper urinary calculi 24 h earlier. All patients had 16 French Foley catheters inserted and the balloons were filled. In group A, the catheters were fixed on the top one-third of the thigh. In group B, the catheters were fixed on the abdominal wall. Patients in whom the catheters were neither fixed on the thigh nor abdominal wall were designated as controls. There were 150 patients in each group. CALUTS, such as frequency, urgency, burning during micturition, odynuria, bladder pain and other symptoms, including urethral discharge, a red and swollen external urethral orifice, catheter traction or blockage and catheter-associated discomfort were recorded. Patients in group A compared with the control group had a significantly lower incidence of frequency, urgency, odynuria, urethral discharge, cathete r traction and catheter-associated discomfort (P<0.05). Patients in group B were observed to have a significantly lower incidence of urgency, urethral discharge, catheter traction and catheter-associated discomfort compared with the control group (P<0.05), but a higher incidence of odynuria, urethral pain, urethral discharge and a red and swollen external urethral orifice compared with group A (P<0.05). An additional catheter fixation site for bedridden patients was necessary and an additional fix site on the thigh was preferred to the abdominal wall, which may further reduce catheter-associated lower urinary tract symptoms.
Keywords: abdominal wall; additional fixation; catheter-associated lower urinary tract symptoms; thigh.
Copyright © 2020, Spandidos Publications.
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14
Exp Ther Med
2021 Jan;21(1):50. doi: 10.3892/etm.2020.9482. Epub 2020 Nov 19.
Effect of fluoxetine on the MAPK-ERK1/2 signaling pathway and expression of associated factors in human conjunctival epithelial cells in culture
Ting Cao 1, Yanning Yang 1, Bin Chen 1, Xiaoxiong Wang 1
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PMID: 33273978 PMCID: PMC7706400 DOI: 10.3892/etm.2020.9482
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Abstract
The aim of the present study was to evaluate the effect of fluoxetine on activation of the mitogen-activated protein kinase (MAPK) signaling pathway and the expression of apoptosis-associated factors in human conjunctival epithelial cells (HConEpiCs) in culture. HConEpiCs were isolated, cultured and characterized by immunostaining. HConEpiC cells at passage 3-4 were cultured with fluoxetine at different dosages (0, 1, 2.5, 5, 10, 20 and 40 µM) and proliferation rates were determined using a Cell Counting Kit-8 assay. Subsequently, Transwell assays were performed to evaluate the effect of fluoxetine (5 µM) on the invasion and migration capacities of HConEpiCs. ERK1/2 and phosphorylated (p-)ERK1/2 levels were also evaluated in control and fluoxetine-treated groups of HConEpiCs via immunostaining. Finally, western blot assays were performed to evaluate the intracellular protein levels of ERK, p-ERK, Bcl-2, Bax and matrix metalloproteinases (MMPs) in HConEpiCs. It was identified that, as the fluoxetine concentration increased, proliferation rates of HConEpiCs gradually decreased and 5 µΜ fluoxetine was selected for further evaluation. The results of Transwell assays indicated that fluoxetine treatment significantly repressed cell migration and invasion. Immunostaining suggested that there was no significant difference in fluorescence intensity of ERK1/2 between the control and fluoxetine-treated groups, while p-ERK1/2 was significantly enhanced in the fluoxetine-treated group. This result indicated that fluoxetine promoted ERK1/2 activation without affecting its expression. Similarly, western blot analysis revealed no significant difference in ERK1/2 and MMP levels between fluoxetine-treated and control groups, but p-ERK1/2 and Bax were upregulated and Bcl-2 was decreased in the fluoxetine-treated group. In conclusion, fluoxetine induces apoptosis of HConEpiCs in culture via activating the MAPK-ERK1/2 signaling pathway.
Keywords: dry eye disease; fluoxetine; mitogen-activated protein kinase.
Copyright: © Cao et al.
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15
Exp Ther Med
2021 Jan;21(1):31. doi: 10.3892/etm.2020.9463. Epub 2020 Nov 11.
Androgen receptor gene mutations in 258 Han Chinese patients with polycystic ovary syndrome
Lifeng Tian 1 2 3, Yang Zou 3 4, Jun Tan 2 3, Yaoqing Wang 1, Jia Chen 1, Leizhen Xia 2, Lixian Xu 3, Ge Chen 3 4, Qiongfang Wu 2 3, Ouping Huang 1 3 5
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PMID: 33262817 PMCID: PMC7690241 DOI: 10.3892/etm.2020.9463
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Abstract
Polycystic ovary syndrome (PCOS) affects 8-13% of reproductive-age females worldwide and mutations or aberrant expression of androgen receptor (AR) may cause the onset of this disease. In the present study, 258 samples from Han Chinese patients with PCOS were analyzed for the presence of AR mutations via sequencing of all coding exons of the AR gene. A total of five heterozygous missense mutations, namely p.V3M, p.Q72R, p.S158L, p.S176R and p.G396R, were identified in five of the patients. Among these, p.S158L was a novel mutation that, to the best of our knowledge, has not been reported previously. Although the remaining four mutations have been reported previously, they existed at low frequencies or were absent in the control subjects and in the Exome Aggregation Consortium database. The results of evolutionary conservation and in silico analysis revealed that the p.V3M, p.S158L and p.S176R mutations were pathogenic, whereas the p.Q72R and p.G396R mutations were benign. Compared wi th the patients with PCOS without AR mutations or with benign AR mutations, markedly lower estrogen levels on the day of human chorionic gonadotropin injection were observed in the three patients with PCOS with potentially pathogenic mutations. In addition, patients with PCOS with pathogenic mutations had lower numbers of oocytes; however, the difference was not statistically significant. Of note, these observations should be interpreted with caution due to the relatively small sample size in the present study. Therefore, a larger number of samples should be collected to validate the results of the present study in future studies. In summary, the present study identified three potential pathogenic mutations in 258 Han Chinese patients with PCOS and these mutations may have an implication in the pathogenesis of PCOS.
Keywords: Han Chinese; androgen receptor; polycystic ovary syndrome; rare variant.
Copyright: © Tian et al.
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16
Exp Ther Med
2021 Jan;21(1):39. doi: 10.3892/etm.2020.9471. Epub 2020 Nov 17.
Role of the stromal cell derived factor-1 in the biological functions of endothelial progenitor cells and its underlying mechanisms
Yanping Cun 1, Bo Diao 2, Zhimin Zhang 1, Gang Wang 2, Jing Yu 2, Lianting Ma 3, Zhiguo Rao 1
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PMID: 33273969 PMCID: PMC7706408 DOI: 10.3892/etm.2020.9471
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Abstract
Stromal cell derived factor-1 (SDF-1) is a chemokine that plays a critical role in the homing of stem and progenitor cells, including endothelial progenitor cells (EPCs). However, little research has been undertaken to evaluate the roles of SDF-1 in the biological functions of EPCs and related signaling pathways. The present study aimed to investigate the biological functions of EPCs in response to SDF-1, as well as the underlying mechanisms. The effects of SDF-1 treatment on EPC proliferation, migration and tube formation were assessed by performing MTS, Transwell and in vitro tube formation assays, respectively. The phosphorylation status of Akt and ERK was evaluated by western blotting. The present results indicated that SDF-1 treatment enhanced EPC proliferation, migration and tube formation compared with the control group. Furthermore, SDF-1-induced EPC proliferation was significantly reduced following treatment with a C-X-C Motif Chemokine Receptor 4 antagonist (AMD3100), a PI3 K inhibitor (LY294002) and the mitogen-activated protein kinase kinase inhibitor (MEK; PD98059). SDF-1-induced migration and angiogenesis were significantly suppressed by the PI3K inhibitor, but not the MEK inhibitor. Moreover, SDF-1 significantly increased the protein expression levels of phosphorylated (p)-Akt and p-ERK; however, SDF-1-induced effects on protein expression were suppressed by AMD3100, LY294002 and PD98059. Thus, SDF-1-induced EPC proliferation was mediated by activation of the Akt and ERK signaling pathways, whereas SDF-1-mediated EPC migration and tube formation only involved activation of the Akt signaling pathway.
Keywords: Akt signaling pathway; ERK signaling pathway; biological functions; endothelial progenitor cells; stromal cell derived factor-1.
Copyright: © Cun et al.
63 references5 figures
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17
Exp Ther Med
2021 Jan;21(1):26. doi: 10.3892/etm.2020.9458. Epub 2020 Nov 9.
Assessment of acute pancreatitis severity via determination of serum levels of hsa-miR-126-5p and IL-6
Ying-Jie Chen 1, Tian-Lai Lin 2, Zhe Cai 3, Chang-Hu Yan 1, Sen-Ren Gou 1, Yao-Dong Zhuang 1
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PMID: 33262812 PMCID: PMC7690249 DOI: 10.3892/etm.2020.9458
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Abstract
Early assessment of acute pancreatitis (AP) severity is key to its treatment. The present study aimed to explore the role of microRNAs (miRNAs/miRs) combined with inflammatory factors in determining AP severity. For this, serum pro-inflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6, IL-8 and IL-10)] and miRNAs [Homo sapiens (hsa)-miR-548d-5p, hsa-miR-126-5p and hsa-miR-130b-5p] were detected in patients with mild AP (MAP), severe AP (SAP) and recurrent AP (RAP). High expression of IL-10, TNF-α, hsa-miR-126-5p, hsa-miR-548d-5p and hsa-miR-130b-5p was able to distinguish SAP from MAP and RAP (P<0.05). Multifactorial binary logistic regression analysis indicated that IL-1/IL-6 combined with hsa-miR-126-5p/hsa-miR-548d-5p had a significant influence on AP and AP severity (P<0.05). Receiver operating characteristic analysis revealed that IL-1 combined with hsa-miR-126-5p [area under the curve (AUC), 0.926; sensitivity, 90.0%; specificity, 86.7%, P<0.001] and IL-6 combined with hsa-miR-126-5p (AUC, 0.952; sensitivity, 93.3%; specificity, 90.0%; P<0.001) were able to better distinguish MAP from SAP than IL-1/IL-6 combined with hsa-miR-548d-5p, lipase, and amylase. IL-1 or IL-6 combined with hsa-miR-548d-5p (AUC, 0.924; sensitivity, 83.3%; specificity, 93.3%; P<0.001) were able to better distinguish SAP from RAP than IL-1/IL-6 combined with hsa-miR-126-5p, lipase, and amylase. IL-1 combined with hsa-miR-126-5p (AUC, 0.926; sensitivity, 90.0%; specificity, 86.7%; P<0.001) and IL-6 combined with hsa-miR-126-5p (AUC, 0.952; sensitivity, 93.3%; specificity, 90.0%; P<0.001) were able to better differentiate between MAP and RAP than IL-1/IL-6 combined with hsa-miR-548d-5p, lipase, and amylase. These results demonstrated that the combined detection of serum IL-6 and hsa-miR-126-5p may be useful for the early prediction of AP classification.
Keywords: acute pancreatitis; inflammatory cytokines; microRNA; predictors; receiver operating characteristic curve.
Copyright: © Chen et al.
37 references4 figures
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18
Exp Ther Med
2021 Jan;21(1):32. doi: 10.3892/etm.2020.9464. Epub 2020 Nov 11.
Transrectal ultrasound-guided seminal vesicle catheterization with continuous antibiotic infusion for the treatment of refractory hematospermia
Ren Wang 1, Lei Chen 1, Xiaojun Bai 1, Tingting Li 1, Dan Wu 2, Jinjin Chen 2
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PMID: 33262818 PMCID: PMC7690242 DOI: 10.3892/etm.2020.9464
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Abstract
The aim of the present study was to describe transrectal ultrasound (TRUS)-guided seminal vesicle catheterizations with continuous antibiotic infusion in patients with persistent hematospermia. A retrospective record review of 45 patients with refractory hematospermia treated with TRUS-guided seminal vesicle catheterization between 2010 and 2017 was performed. Seminal vesicle puncture and catheterization was performed under TRUS guidance for all patients. Antibiotic irrigation was used to rinse the seminal vesicle until the outflow fluid was clear. The trocar sleeve was left in situ and fixed on the skin of the perineum at the end of the procedure. All patients underwent a 24-h continuous infusion of antibiotic solution through the catheter. The patients were followed up to 3 years for the presence of hematospermia. The duration of refractory hematospermia was between 6 months and 9 years. A total of 14 patients exhibited consecutive hematospermia, while the remaining patients exhibi ted intermittent episodes. On TRUS, 15 cases of ejaculatory duct cyst, 7 cases of ejaculatory duct expansion, 3 cases of ejaculatory duct stones, 6 cases of seminal vesicle expansion, 8 cases of seminal vesicle stones and 5 cases of seminal vesicle wall or ejaculation wall calcification were diagnosed. A total of 41 patients completed the scheduled treatment plan; however, the catheter was dissociated on the 3rd or 4th day of catheterization in 4 patients. After a 1-3 year follow-up, hematospermia was not observed in 42 patients (93.33%) with recurrence in the remaining 3 patients. In conclusion, TRUS-guided seminal vesicle catheterization with continuous antibiotic infusion appeared to be a safe and effective method for the treatment of hematospermia.
Keywords: catheterization; hematospermia; transrectal ultrasound; treatment.
Copyright: © Wang et al.
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19
Exp Ther Med
2021 Jan;21(1):40. doi: 10.3892/etm.2020.9472. Epub 2020 Nov 17.
Giant aneurysm of the bilateral vertebrobasilar junction treated by pipeline and coils: A case report and literature review
Chun-Lei Zhang 1, Zhong-Hua Shi 1, Zhi-Zhong Yan 1, Chun-Long Ding 1, Jia-Ming Cao 1, Yu-Hai Wang 1, Peng Zhang 2
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PMID: 33273970 PMCID: PMC7706383 DOI: 10.3892/etm.2020.9472
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Abstract
Giant aneurysm of the posterior circulation is associated with a higher risk of rupture compared with that of the anterior circulation. Furthermore, surgical clipping and interventional embolization for giant aneurysm of the posterior circulation are more difficult and complex to perform. The present study reported on the case of a 26-year-old female who exhibited a giant spherical aneurysm of the vertebrobasilar junction (VBJ) with a maximum diameter of ~35 mm that caused cervical discomfort. In addition, the patient experienced symptoms including left-sided walking and hoarseness caused by the compression of the brainstem and the posterior cranial nerves. The risks associated with performing surgery in this area are high and the prognosis is mainly poor. The patient of the present study was treated using the Pipeline Flex device with coil embolization. As a giant aneurysm of the VBJ simultaneously affects the bilateral vertebral arteries (VAs) and basilar artery, it is a unique con dition and the treatment strategy must be personalized. Based on an analysis of the hemodynamic influence on the aneurysm in the present case, the Pipeline was placed through the left VA, the coils were packed through the right VA, and finally, the right VA was proximally occluded. At 7 months after embolization, the patient's modified Rankin scale score was 1 point. Upon analysis of the hemodynamic influence on the aneurysm of the VBJ, the VA with the larger shear force on the wall of the aneurysm was selected for occlusion to simplify the treatment of the aneurysm and to maximize the probability to achieve recovery.
Keywords: endovascular treatment; giant aneurysm; pipeline embolization device; vertebrobasilar junction.
Copyright: © Zhang et al.
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20
Exp Ther Med
2021 Jan;21(1):42. doi: 10.3892/etm.2020.9474. Epub 2020 Nov 17.
Diagnostic accuracy of true fast imaging with steady-state precession, MR pulmonary angiography and volume-interpolated body examination for pulmonary embolism compared with CT pulmonary angiography
Qing Fu 1 2, Qiguang Cheng 1 2, Xiangchuang Kong 1 2, Hui Ma 1 2, Ziqiao Lei 1 2
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PMID: 33273972 PMCID: PMC7706389 DOI: 10.3892/etm.2020.9474
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Abstract
The diagnostic performance of magnetic resonance (MR) sequences for displaying different levels of pulmonary artery involvement in pulmonary embolism (PE) has rarely been reported but is essential for critically ill and emergency patients. The aim of the present study was to analyze the diagnostic accuracy of true fast imaging with steady-state precession (true FISP), MR pulmonary angiography (MRPA) and volume-interpolated body examination (VIBE) for PE detection in comparison to CT pulmonary angiography (CTPA), which is the reference standard. A total of 21 patients with confirmed deep venous thrombosis suspected of having PE were enrolled. Emboli were evaluated on per-patient and per-vessel bases. The evidence of PE on a per-vessel basis was classified into central, lobar and segmental levels, and 27 vessel segments per patient were analyzed for a total of 567 vessel segments in all patients. The sensitivity, specificity, positive predictive value (PPV) and negative predictive valu e (NPV) were calculated. Receiver operating characteristic curves were drawn to compare differences in sequences. A total of 158 pulmonary vessels were involved with emboli on CTPA, 58 of which were identified by true FISP, 63 by MRPA and 94 by VIBE. On per-patient and per-vessel bases, the sensitivity was 81.3 and 36.7%, respectively, for true FISP, 82.4 and 56.3%, respectively, for MRPA, and 94.4 and 68.1%, respectively, for VIBE; the specificity was 80.0 and 99.8%, respectively, for true FISP, 100 and 99.2%, respectively, for MRPA, and 100 and 99.2%, respectively, for VIBE. The respective PPV was 92.9 and 98.3% for true FISP, 100 and 95.5% for MRPA, 100 and 96.9% for VIBE. The NPV was 57.1 and 80.3%, respectively, for true FISP, 50.0 and 88.2%, respectively, for MRPA, and 75.0 and 89.8%, respectively, for VIBE. In conclusion, enhanced VIBE surpassed the other two sequences in revealing PE, particularly in segmental analysis, which is essential for emergency patients who have cont raindications for receiving iodinated contrast and those who have concerns about the ionizing radiation.
Keywords: CT angiography; MR angiography; MRI; pulmonary embolism; volume-interpolated body examination.
Copyright: © Fu et al.
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