Page 1
Select search result to email or save
1
Exp Ther Med
. 2020 Jul;20(1):409-417. doi: 10.3892/etm.2020.8698. Epub 2020 Apr 29.
IL-17 Aggravates Renal Injury by Promoting Podocyte Injury in Children With Primary Nephrotic Syndrome
Shubo Zhai 1, Baichao Sun 1, Yan Zhang 1, Lengyue Zhao 1, Li Zhang 1
Affiliations expand
PMID: 32537005 PMCID: PMC7282090 DOI: 10.3892/etm.2020.8698
Free PMC article
Abstract
Primary nephrotic syndrome (PNS) is the most common chronic kidney disease in childhood, where podocyte injury is a key factor in the occurrence of kidney disease. In the present study, the expression of IL-17 in renal tissues of patients with PNS and its relationship with podocyte injury were examined. Reverse transcription-quantitative PCR (RT-qPCR), western blot analysis and immunochemistry were used to measure the expression of IL-17 in renal biopsies of patients with ONS, including 9 patients with minimal change nephrotic syndrome (MCNS), 15 patients with mesangial proliferative glomerulonephritis (MsPGN) and 9 patients with focal segmental glomerulosclerosis (FSGS), in addition to 15 normal kidney tissues. IL-17 was found to be highly expressed in the renal tissues from patients with PNS, with the highest expression levels found in tissues from patients with FSGS and the lowest in those from MCNS. A negative correlation was observed between the levels of IL-17 mRNA and PCX mRNA in renal tissues, whereas a positive correlation between IL-17 mRNA levels and the number of urinary podocytes in patients with PNS was found. In vitro, IL-17 induced podocyte apoptosis and reduced the expression of markers associated with podocytes, including Wilm's tumor 1, nephrin, synaptopodin and podocalyxin, whilst increasing the levels of Fas, Fas ligand (FasL), active-caspase-8, active-caspase-3 and phosphorylated-p65. However, treatment with helenalin, a NF-κB inhibitor, decreased p65 phosphorylation, attenuated IL-17-induced podocyte apoptosis and suppressed the IL-17-activated Fas/FasL/caspase-8/caspase-3 apoptotic pathway. Taken together, these observations suggest that IL-17 was highly expressed in renal tissues from patients with PNS, where it induced podocyte apoptosis by activating the Fas/FasL/caspase-8/caspase-3 apoptotic pathway in a NF-κB-dependent manner.

Keywords: children; interleukin-17; podocyte; primary nephrotic syndrome.

Copyright: © Zhai et al.

51 references5 figures
full-text links
Proceed to details Cite
 Share
2
Exp Ther Med
. 2020 Jul;20(1):599-606. doi: 10.3892/etm.2020.8699. Epub 2020 Apr 29.
Assessment of the Sedative Effects of Dexmedetomidine and Propofol Treatment in Patients Undergoing Mechanical Ventilation in the ICU and Relationship Between Treatment and Occurrence of Ventilator-Associated Pneumonia and Detection of Pathogenic Bacteria
Hongjie Dou 1, Fangbao Hu 1, Wen Wang 1, Lin Ling 1, Deqiang Wang 1, Fenlian Liu 1
Affiliations expand
PMID: 32537018 PMCID: PMC7282099 DOI: 10.3892/etm.2020.8699
Free PMC article
Abstract
The present study aimed to investigate the sedative effects of dexmedetomidine combined with propofol in patients undergoing mechanical ventilation in the intensive care unit (ICU), and to reveal the risk factors of ventilator-associated pneumonia (VAP). A retrospective analysis of 322 patients who had been subject to mechanical ventilation in the ICU ward was performed. Subjects were divided into two groups: A group treated with dexmedetomidine and propofol (combined group) and a group treated with dexmedetomidine alone (monotherapy group). Clinical data, sedative effects, the number of VAP patients and the distribution of VAP pathogens were assessed. Multivariate analysis and receiver operating characteristic (ROC) curves were used to predict VAP. Significant differences in the sedative effects between the two groups were observed (P<0.001). The incidence of VAP was significantly higher in the monotherapy group compared with the combined group (P<0.05). Multivariate logistic regression analysis demonstrated that age, acute physiology chronic health evaluation score, consciousness, invasive operations, recovery time, extubation time and sedation regimen were independent risk factors for VAP in the ICU during mechanical ventilation. ROC curves indicated that the areas under the curve for age, acute physiology chronic health score, consciousness, invasive operations, recovery time, extubation time and sedation regimen were 0.934, 0.870, 0.632, 0.677, 0.865, 0.950 and 0.603, respectively. In summary, dexmedetomidine combined with propofol can shorten the recovery and extubation times of mechanical ventilation patients in the ICU. Different sedation schemes are also independent risk factors for VAP during mechanical ventilation in the ICU.

Keywords: dexmedetomidine; intensive care unit; mechanical ventilation; propofol; ventilator-associated pneumonia.

Copyright © 2020, Spandidos Publications.

1 figure
full-text links
Proceed to details Cite
 Share
3
Review Exp Ther Med
. 2020 Jul;20(1):163-172. doi: 10.3892/etm.2020.8731. Epub 2020 May 8.
Role of the Lysyl Oxidase Family in Organ Development (Review)
Shanzun Wei 1 2, Liang Gao 1 2, Changjing Wu 1, Feng Qin 1, Jiuhong Yuan 1 2
Affiliations expand
PMID: 32536990 PMCID: PMC7282176 DOI: 10.3892/etm.2020.8731
Free PMC article
Abstract
Lysyl oxidase proteins (LOXs) are amine oxidases, which are mainly located in smooth muscle cells and fibroblasts and serve an important role in the formation of the extracellular matrix (ECM) in a copper-dependent manner. Owing to the ability of LOX proteins to modulate crosslinking between collagens and to promote the deposition of other fibers, they serve crucially in organogenesis and the subsequent organ development, as well as disease initiation and progression. In addition, ECM formation significantly influences organ morphological formation in both cancer- and non-tumor-related diseases, in addition to cellular epigenetic transformation and migration, under the influence of LOXs. A number of different signaling pathways regulate the LOXs expression and their enzymatic activation. The tissue remodeling and transformation process shares some resemblance between oncogenesis and embryogenesis. Additionally the roles that LOXs serve appeared to be stressed during oncogenesis and tumor metastasis. It has also been indicated LOXs have a noteworthy role in non-tumor diseases. Nonetheless, the role of LOXs in systemic or local organ development and disease control remains unknown. In the present study, the essential roles that LOXs play in embryogenesis were unveiled partially, whereas the role of LOXs in organ or systematic development requires further investigations. The present review aimed to discuss the roles of members of the LOX family in the context of the remodeling of organogenesis and organ development. In addition, the consequences of the malfunction of these proteins related to the development of abnormalities and resulting diseases is discussed.

Keywords: collagen crosslinking; development; extracellular matrix remodeling; lysyl oxidase; organogenesis.

Copyright: © Wei et al.

101 references1 figure
supplementary info
Publication typesexpand
full-text links
Proceed to details Cite
 Share
4
Review Exp Ther Med
. 2020 Jul;20(1):151-158. doi: 10.3892/etm.2020.8704. Epub 2020 Apr 30.
IgY - Turning the Page Toward Passive Immunization in COVID-19 Infection (Review)
Carolina Constantin 1 2, Monica Neagu 1 2 3, Teodora Diana Supeanu 4, Viorica Chiurciu 4, Demetrios A Spandidos 5
Affiliations expand
PMID: 32536989 PMCID: PMC7282020 DOI: 10.3892/etm.2020.8704
Free PMC article
Abstract
The world is facing one of the major outbreaks of viral infection of the modern history, however, as vaccine development workflow is still tedious and can not control the infection spreading, researchers are turning to passive immunization as a good and quick alternative to treat and contain the spreading. Within passive immunization domain, raising specific immunoglobulin (Ig)Y against acute respiratory tract infection has been developing for more than 20 years. Far from being an obsolete chapter we will revise the IgY-technology as a new frontier for research and clinic. A wide range of IgY applications has been effectively confirmed in both human and animal health. The molecular particularities of IgY give them functional advantages recommending them as good candidates in this endeavor. Obtaining specific IgY is sustained by reliable and nature friendly methodology as an alternative for mammalian antibodies. The aria of application is continuously enlarging from bacterial and viral infections to tumor biology. Specific anti-viral IgY were previously tested in several designs, thus its worth pointing out that in the actual COVID-19 pandemic context, respiratory infections need an enlarged arsenal of therapeutic approaches and clearly the roles of IgY should be exploited in depth.

Keywords: COVID-19; IgY; acute respiratory infection; immunoglobulin.

Copyright: © Constantin et al.

90 references1 figure
supplementary info
Publication typesexpand
full-text links
Proceed to details Cite
 Share
5
Exp Ther Med
. 2020 Jul;20(1):418-426. doi: 10.3892/etm.2020.8719. Epub 2020 May 6.
Expression and Role of miR-338-3p in Peripheral Blood and Placenta of Patients With Pregnancy-Induced Hypertension
Jun Li 1, Yan Wu 2, Hui Liu 1
Affiliations expand
PMID: 32537006 PMCID: PMC7282187 DOI: 10.3892/etm.2020.8719
Free PMC article
Abstract
The present study aimed to investigate the role of miR-338-3p in pregnancy-induced hypertension (PIH), and its effects on human trophoblast cells in vitro. Quantitative real-time PCR was used to detect miR-338-3p expression. Human trophoblast HTR8/SVneo cells were transfected with miR-338-3p mimics. Effects of miR-338-3p on cell proliferation, invasion and metastasis, and anoikis resistance were detected by CCK-8 assay, Transwell chamber assay, flow cytometry and western blot analysis, respectively. Bioinformatics analysis was performed to predict the target of miR-338-3p, and the results were confirmed by dual luciferase reporter assay. The expression level of miR-338-3p was significantly upregulated in the peripheral blood and placenta of PIH patients. CCK-8 assay showed that miR-338-3p mimics inhibited the proliferation of HTR8/SVneo cells at indicated time points. Flow cytometry showed that miR-338-3p transfection significantly increased the Ki-67 expression in the HTR8/SVneo cells, indicating enhanced cell proliferation. Transwell chamber assay and western blot analysis showed that the invasion and metastatic abilities of the HTR8/SVneo cells were significantly decreased in the miR-338-3p transfection group, as well as expression levels of MMP-2 and MMP-9. Bioinformatics analysis and dual luciferase reporter assay indicated that AKT3 is a target gene of miR-338-3p. Our results suggest that miR-338-3p is significantly increased in the peripheral blood and placenta of PIH patients, which is correlated with the disease development. miR-338-3p inhibits proliferation, invasion and metastasis, and apoptosis resistance of human trophoblast cells by targeting AKT3.

Keywords: AKT3; miR-338-3p; peripheral blood; placenta; pregnancy-induced hypertension.

Copyright: © Li et al.

34 references6 figures
full-text links
Proceed to details Cite
 Share
6
Exp Ther Med
. 2020 Jul;20(1):195-204. doi: 10.3892/etm.2020.8694. Epub 2020 Apr 29.
Association Between Nod-like Receptor Protein 3 Inflammasome and Gouty Nephropathy
Yan-Zi Zhang 1, Xiao-Lu Sui 1, Yun-Peng Xu 1, Feng-Juan Gu 1, Ai-Sha Zhang 1, Ji-Hong Chen 1
Affiliations expand
PMID: 32536991 PMCID: PMC7281944 DOI: 10.3892/etm.2020.8694
Free PMC article
Abstract
Crystalized deposits of monosodium urate activate the Nod-like receptor protein 3 (NLRP3) inflammasome, resulting in kidney damage. The present study investigated whether the NLRP3 inflammasome is associated with the progression of hyperuricaemia and gouty nephropathy. Adult male patients were recruited at the Affiliated Baoan Hospital of Shenzhen and divided into three groups of 15 patients each: The control group, the hyperuricaemia group and the gouty nephropathy group. General characteristics and organ function indicators were also measured for each patient. NLRP3, apoptosis-associated speck like protein (ASC) and caspase-1 mRNA and protein expressions in peripheral blood mononuclear cells were detected. The expression of certain downstream inflammatory factors, including interleukin (IL)-1β and IL-18 were also assessed in plasma. The results demonstrated that the concentration of uric acid and creatinine were increased in the hyperuricaemia and gouty nephropathy groups compared with the control group. NLRP3, ASC and caspase-1 mRNA and protein expression, and IL-1β and IL-18 expression were increased in the hyperuricaemia and gouty nephropathy groups compared with the control group. In addition, ASC and caspase-1 mRNA and protein expression, and IL-1β expression were higher in the gouty nephropathy group compared with the hyperuricaemia group. In conclusion, the present results supported the hypothesis that the NLRP3 inflammasome signalling pathway is associated with gouty nephropathy leading to initiation of the inflammatory response and causing renal damage.

Keywords: Nod-like receptor protein 3 inflammasome; gouty nephropathy; hyperuricaemia.

Copyright: © Zhang et al.

40 references5 figures
full-text links
Proceed to details Cite
 Share
7
Exp Ther Med
. 2020 Jul;20(1):630-636. doi: 10.3892/etm.2020.8720. Epub 2020 May 6.
Sulfated Modification, Characterization and Monosaccharide Composition Analysis of Undaria pinnatifida Polysaccharides and Anti-Tumor Activity
Fu-Ling Wang 1 2, Yu-Bin Ji 1 2, Bo Yang 1 2
Affiliations expand
PMID: 32537020 PMCID: PMC7282060 DOI: 10.3892/etm.2020.8720
Free PMC article
Abstract
Undaria pinnatifida (U. pinnatifida) polysaccharides (UPPS) are considered to be the major bioactive components of U. pinnatifida. The aim of the present study was to investigate the separation, sulfated modification, characterization and monosaccharide composition of UPPS. The optimal processing conditions were as follows: Distilled water-to-solid ratio, 50 ml/g; extraction time, 300 min; and extraction temperature, 90˚C. The major polysaccharide fraction of U. pinnatifida (UPPS-B1) was purified via DEAE-52 and Sephadex G-200 column chromatography. The chlorosulfonic acid-pyridine method was applied for sulfation modification. UPPS-B1 and sulfated (S)-UPPS-B1 were characterized via chemical analysis, ultraviolet-visible and Fourier-transformed infrared spectroscopy, gas chromatography and high-performance liquid chromatography. The total sugar content of UPPS-B1 and S-UPPS-B1 was 79.78 and 77.28%, respectively. The sulfate radical content of UPPS-B1 and S-UPPS-B1 was 8.53 and 29.12%, whilst the content of uronic acid was 9.29 and 7.98%, respectively. The average molecular weight of UPPS-B1 and S-UPPS-B1 was determined to be 37 and 110 kD, respectively. UPPS-B1 was considered to be a heteropolysaccharide composed of xylose, mannose, glucose and galactose at a ratio of 7.9:8.7:12.0:9.8. In addition, S-UPPS-B1 was a heteropolysaccharide composed of xylose, mannose, glucose and galactose at a ratio of 1.0:9.7:6.4:1.6. The results of the tumor growth inhibition experiment demonstrated that UPPS-B1 exhibited anti-tumor activity in vivo, which was improved following sulfation to yield S-UPPS-B1.

Keywords: Undaria pinnatifida; antitumor activity; characterization; monosaccharide composition; polysaccharides; sulfated modification.

Copyright © 2020, Spandidos Publications.

5 figures
full-text links
Proceed to details Cite
 Share
8
Exp Ther Med
. 2020 Jul;20(1):315-324. doi: 10.3892/etm.2020.8697. Epub 2020 Apr 29.
Clinical Significance of HDAC1, -2 and -3 Expression Levels in Esophageal Squamous Cell Carcinoma
Huiwu Li 1, Hui Li 2, Yibulayin Waresijiang 3, Yan Chen 4, Ying Li 4, Liang Yu 1, Yike Li 5, Ling Liu 4
Affiliations expand
PMID: 32536999 PMCID: PMC7282189 DOI: 10.3892/etm.2020.8697
Free PMC article
Abstract
The present study analyzed the expression of the histone deacetylase (HDAC) 1, 2 and 3 in primary esophageal squamous cell carcinoma (ESCC) samples and how their levels correlate with clinicopathological parameters. ESCC patients (n=88) in the present study had received no previous treatment before undergoing surgical excision. The mRNA expression of HDAC1, -2 and -3 were detected by semi-quantified PCR in ESCC samples and distal normal samples. The relationship of HDAC1, -2 and -3 expression with clinicopathological parameters was analyzed by χ2 test. The correlation among these HDACs was analyzed by Pearson's correlation test. Compared with distal normal tissues, ESCC samples had higher expression of HDAC1, but not HDAC2 or HDAC3 (P<0.05). The expression of HDACs was different between Kazak and Han ethnicities. The expression of HDAC2 was correlated with invasion depth (P<0.05), but not with sex, age, metastasis, or the degree of tumor differentiation (P>0.05). There was no association between HDAC1 or HDAC3 and clinicopathological parameters (P>0.05). For the Kazak and Han ethnicities, HDAC1 expression was present in male patients, patients with well/moderate differentiated ESCC and T3 and T4 ESCC (P<0.01). HDAC1 in patients aged <60 was associated with ethnicity (P<0.05). HDAC2 expression was different in positive LN metastasis, well/moderate differentiation and T3 and T4 ESCC (P<0.01). HDAC3 expression in male patients, patients with negative LN metastasis and well/moderate differentiation ESCC was associated with ethnicity (P<0.05). Additionally, the expression levels of HDAC1, -2 and -3 did not correlate with each other. Thus, HDAC1 expression may be used as a risk factor for ESCC and HDAC2 levels may be used to predict invasion depth. The expression of HDAC1, -2 and -3 has ethnic differences.

Keywords: esophageal squamous cell carcinoma; histone deacetylase 1; histone deacetylase 2; histone deacetylase 3.

Copyright: © Li et al.

54 references2 figures
full-text links
Proceed to details Cite
 Share
9
Exp Ther Med
. 2020 Jul;20(1):543-549. doi: 10.3892/etm.2020.8728. Epub 2020 May 7.
Virological Investigation of Genetic Variation of Enterovirus Type 71 in Hand, Foot and Mouth Disease
Yang Wang 1, Yi Li 1, Yuling Yang 2, Chuanmei Peng 1, Xiaoye Fu 1, Xin Gu 1, Hui Gao 1
Affiliations expand
PMID: 32537012 PMCID: PMC7281934 DOI: 10.3892/etm.2020.8728
Free PMC article
Abstract
The aim of the present study was to analyze the sequence of the VP1 gene in enterovirus 71 (EV71) isolates and to explore their genetic evolution, so as to provide a scientific basis for the clinical prevention and treatment of hand, foot and mouth disease. The fecal samples of 590 patients with suspected hand, foot and mouth disease treated at Yan'an Hospital (Kunming, China) between January 2015 and December 2016 were collected and EV71 nucleic acid was detected by fluorescence PCR. The viral RNA of EV71-positive samples was extracted, the VP1 gene was amplified by PCR and the products were sequenced. The VP1 gene sequence was analyzed using DNAMAN and MEGA (version 4.0) software and homologous modeling was performed using Pymol software. A total of 50 EV71-positive samples were identified and the detection rate was 8.47% (50/590 cases). All of the 50 EV71 strains were of the C4 subtype. The genetic distance between the strains detected in the present study and EV71 strains detected in Beijing, Anhui and Malaysia was 0.01-0.03, while that between the strains detected in the present study and Australian strains was 2.11. Homologous modeling indicated that the amino acid sequence of the VP1 gene of the detected strains had a H144Y mutation. There was no significant genetic variation in the EV71 strain within the 2-year period. In conclusion, the EV71 strains detected in the present study was similar to that detected in Beijing, Anhui and Malaysia but different to that from Australia. A point mutation was present in the amino acid sequence of the VP1 gene.

Keywords: enterovirus 71; foot and mouth disease; hand; homology modeling; phylogenetic tree; viral envelope protein 1.

Copyright: © Wang et al.

26 references4 figures
full-text links
Proceed to details Cite
 Share
10
Exp Ther Med
. 2020 Jul;20(1):427-435. doi: 10.3892/etm.2020.8722. Epub 2020 May 6.
Bioinformatics Analysis Reveals Meaningful Markers and Outcome Predictors in HBV-associated Hepatocellular Carcinoma
Lijie Zhang 1, Joyman Makamure 1, Dan Zhao 1, Yiming Liu 1, Xiaopeng Guo 1, Chuansheng Zheng 1, Bin Liang 1
Affiliations expand
PMID: 32537007 PMCID: PMC7281962 DOI: 10.3892/etm.2020.8722
Free PMC article
Abstract
Hepatocellular carcinoma (HCC) is the most common type of malignant neoplasm of the liver with high morbidity and mortality. Extensive research into the pathology of HCC has been performed; however, the molecular mechanisms underlying the development of hepatitis B virus-associated HCC have remained elusive. Thus, the present study aimed to identify critical genes and pathways associated with the development and progression of HCC. The expression profiles of the GSE121248 dataset were downloaded from the Gene Expression Omnibus database and the differentially expressed genes (DEGs) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) analyses were performed by using the Database for Annotation, Visualization and Integrated Discovery. Subsequently, protein-protein interaction (PPI) networks were constructed for detecting hub genes. In the present study, 1,153 DEGs (777 upregulated and 376 downregulated genes) were identified and the PPI network yielded 15 hub genes. GO analysis revealed that the DEGs were primarily enriched in 'protein binding', 'cytoplasm' and 'extracellular exosome'. KEGG analysis indicated that DEGs were accumulated in 'metabolic pathways', 'chemical carcinogenesis' and 'fatty acid degradation'. After constructing the PPI network, cyclin-dependent kinase 1, cyclin B1, cyclin A2, mitotic arrest deficient 2 like 1, cyclin B2, DNA topoisomerase IIα, budding uninhibited by benzimidazoles (BUB)1, TTK protein kinase, non-SMC condensin I complex subunit G, NDC80 kinetochore complex component, aurora kinase A, kinesin family member 11, cell division cycle 20, BUB1B and abnormal spindle microtubule assembly were identified as hub genes based on the high degree of connectivity by using Cytoscape software. In addition, overall survival (OS) and disease-free survival (DFS) analyses were performed using the Gene Expression Profiling Interactive Analysis online database, which revealed that the increased expression of all hub genes were associated with poorer OS and DFS outcomes. Receiver operating characteristic curves were constructed using GraphPad prism 7.0 software. The results confirmed that 15 hub genes were able to distinguish HCC form normal tissues. Furthermore, the expression levels of three key genes were analyzed in tumor and normal samples of the Human Protein Atlas database. The present results may provide further insight into the underlying mechanisms of HCC and potential therapeutic targets for the treatment of this disease.

Keywords: bioinformatics analysis; biomarker; differentially expressed genes; hepatitis B virus; hepatocellular carcinoma.

Copyright: © Zhang et al.

49 references6 figures
full-text links
Proceed to details Cite
 Share
11
Exp Ther Med
. 2020 Jul;20(1):269-274. doi: 10.3892/etm.2020.8710. Epub 2020 Apr 30.
Changes in MMP-2, MMP-9, Inflammation, Blood Coagulation and Intestinal Mucosal Permeability in Patients With Active Ulcerative Colitis
Xuesong Bai 1, Guang Bai 1, Lidong Tang 1, Lin Liu 1, Yufeng Li 1, Wei Jiang 1
Affiliations expand
PMID: 32536995 PMCID: PMC7282134 DOI: 10.3892/etm.2020.8710
Free PMC article
Abstract
Changes in matrix metalloproteinase (MMP)-2, MMP-9, inflammation, blood coagulation factors and intestinal mucosal permeability in patients with active ulcerative colitis (UC) were investigated. A total of 50 active UC patients treated in our hospital from January 2016 to December 2018 were selected as the UC group, whereas 50 normal subjects receiving physical examination were selected as the control group. Venous blood was drawn to detect the content of early predictors, C-reactive protein (CRP), follistatin-like protein 1 (FSTL1) and D-dimer in serum. The disease activity index (DAI) score was recorded in both groups, the levels of MMP-2 and MMP-9 were determined, and the inflammatory factors interleukin (IL)-1, IL-6 and tumor necrosis factor (TNF)-α were also detected. Moreover, the blood coagulation factors, platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen level were detected, the content of lactulose (L) and mannitol (M) in the urine after oral administration of L and M test liquid was determined via high-performance liquid chromatography in both groups, and the L/M ratio was calculated. In UC group, the content of CRP, FSTL1 and D-dimer was significantly higher than that in the control group (P<0.05). The DAI score was significantly higher (P<0.05), the content of MMP-2 and MMP-9 was remarkably raised (P<0.05), the platelet count, PT, APTT and fibrinogen level were all obviously increased (P<0.05), and the L/M ratio was notably lower (P<0.05) in the UC group than in the control group. In patients with active UC, MMP-2, MMP-9 and inflammatory factors were significantly increased, and there were changes in the blood coagulation factors and intestinal mucosal permeability, which further promote the occurrence and development of UC.

Keywords: MMP-2; MMP-9; active phase; blood coagulation factors; inflammatory factors; intestinal mucosal permeability; ulcerative colitis patients.

Copyright: © Bai et al.

26 references3 figures
full-text links
Proceed to details Cite
 Share
12
Exp Ther Med
. 2020 Jul;20(1):275-282. doi: 10.3892/etm.2020.8696. Epub 2020 Apr 29.
Protective Effect of Puerarin Against Burn-Induced Heart Injury in Rats
Junling Liu 1, Jianyun Liu 1, Mingming Bai 1, Hui Wang 1
Affiliations expand
PMID: 32536996 PMCID: PMC7282049 DOI: 10.3892/etm.2020.8696
Free PMC article
Abstract
The present study evaluated the potential protective effects of puerarin and its associated mechanism on burn-induced myocardial damage. A total of 40 healthy adult Wistar rats were randomly divided into four groups: i) Sham; ii) burn; iii) burn + puerarin; and iv) puerarin. Serum levels of interleukin (IL)-1β, tumor necrosis factor-α (TNF-α) and IL-6 were measured using ELISA. Myeloperoxidase (MPO) activity and malondialdehyde (MDA) levels were determined in myocardial homogenates using a commercial assay kit. TUNEL staining and western blot analysis of cleaved and pro-caspase-3 were also performed to assess apoptosis. Activation of p38-MAPK, ERK, JNK and AKT were measured using western blot analysis. Left ventricular systolic pressure, maximum rates of increase/decrease in left ventricular pressure, creatine kinase MB activity and cardiac troponin T levels were found to be altered in the burn group 12 h after burn, which were reversed by puerarin treatment. Injection of puerarin following burn injury also reduced heart water content. Serum levels of IL-1β, TNF-α and IL-6 were significantly higher in the burn group compared with those in the sham group. Puerarin treatment reduced serum levels of IL-1β, TNF-α and IL-6, in addition to reducing MPO activity and MDA levels in myocardial tissues. Puerarin inhibited the activation of caspase-3, p38, ERK and JNK following severe burn, but elevated Akt activation following severe burn. In conclusion, puerarin improved cardiac function in rats following severe burn injury, which may be due to reduced myocardial injury, inhibition of cardiomyocyte apoptosis and reduced oxidative inflammatory stress; the MAPK and AKT signaling pathways are proposed to the underlying mechanism of these findings.

Keywords: burns; cardiac dysfunction; inflammation; myocardial injury; p38-MAPK; puerarin.

Copyright: © Liu et al.

56 references4 figures
full-text links
Proceed to details Cite
 Share
13
Exp Ther Med
. 2020 Jul;20(1):550-560. doi: 10.3892/etm.2020.8733. Epub 2020 May 8.
Rosuvastatin Protects Against Endothelial Cell Apoptosis in vitro and Alleviates Atherosclerosis in ApoE -/- Mice by Suppressing Endoplasmic Reticulum Stress
Jianan Geng 1, Huali Xu 1, Wenwen Fu 1, Xiaofeng Yu 1, Guoliang Xu 2, Hongyan Cao 2, Guangzhu Lin 2, Dayun Sui 1
Affiliations expand
PMID: 32537013 PMCID: PMC7282009 DOI: 10.3892/etm.2020.8733
Free PMC article
Abstract
The development of abnormal lipid-induced atherosclerosis is initiated with endothelial cell apoptosis. Vascular endothelial cells possess highly developed endoplasmic reticulum (ER), which is involved in lipid metabolism, indicating that ER stress may contribute chiefly to the induction of endothelial cell apoptosis. Based on its ability to reduce cholesterol levels, rosuvastatin may play an endothelial and vascular protective role by regulating ER stress. In the present study, the involvement of the inhibition of the ER stress-induced endothelial injury was investigated in combination with the lipid lowering effects of rosuvastatin. This compound can be used to inhibit cholesterol synthesis in atherosclerosis. Rosuvastatin decreased the apoptotic rates of human umbilical vascular endothelial cells (HUVECs) that had been stimulated with ox-low density lipoprotein (LDL) in vitro and repressed the mRNA levels of CHOP, sXBP1 and caspase-12, and decreased caspase-12 activity, as well as the content of glucose-regulated protein 78 (GRP78), phosphorylated (p)-protein kinase RNA-like ER kinase (PERK), p-inositol-requiring protein 1α (IRE1α) and p-eIF2α proteins. In addition, ApoE-/- mice were fed with atherogenic chow for 8 weeks for atherosclerosis induction and rosuvastatin was provided by intragastric administration for an additional 4 weeks. Subsequently, the atherosclerotic plaque formation in the aorta was evaluated by Oil Red O and hematoxylin and eosin staining, and the serum LDL, high-density lipoprotein, total cholesterol (TC) and triacylglycerol (TG) levels were measured. In addition, the induction of apoptosis of endothelial cells and the expression levels of GRP78, p-PERK, p-IRE1α and p-eIF2α were assessed in the aorta. Rosuvastatin repressed atherosclerotic plaque formation and endothelial apoptosis in the aorta and decreased LDL and TG levels in the serum, as determined by in vivo results. Furthermore, it downregulated the expression levels of protein chaperone GRP78, p-PERK, p-IRE1α and p-eIF2α in the aortic intima. The data indicated that rosuvastatin could protect HUVECs from ER stress-induced apoptosis triggered by oxidized LDL. It could also inhibit atherosclerosis formation in ApoE-/- mice aorta by regulating the PERK/eIF2α/C/EBPα-homologous protein and IRE1α/sXBP1 signaling pathways. Taken collectively, the present study demonstrated the preventive and therapeutic effects of rosuvastatin in protecting from the development of endothelial cell dysfunction diseases.

Keywords: atherosclerosis; endoplasmic reticulum stress; endothelial cell apoptosis; rosuvastatin.

Copyright: © Geng et al.

38 references7 figures
full-text links
Proceed to details Cite
 Share
14
Exp Ther Med
. 2020 Jul;20(1):591-598. doi: 10.3892/etm.2020.8725. Epub 2020 May 7.
Loganin Attenuates Intestinal Injury in Severely Burned Rats by Regulating the Toll-Like Receptor 4/NF-κB Signaling Pathway
Hailing Wen 1, Liang Xing 2, Kui Sun 1, Changshuan Xiao 1, Xiangxi Meng 1, Jingzhe Yang 1
Affiliations expand
PMID: 32537017 PMCID: PMC7281942 DOI: 10.3892/etm.2020.8725
Free PMC article
Abstract
Severe burns may lead to intestinal inflammation and oxidative stress, resulting in intestinal barrier damage and gut dysfunction. Loganin, an iridoid glycoside compound, has been isolated from Cornus officinalis Sieb. et Zucc; however, its role in the treatment of burn injury is yet to be fully elucidated. Therefore, the present study examined the effect of loganin administration on burn-induced intestinal inflammation and oxidative stress after severe burns in male Sprague-Dawley rats. Histological injury was assessed by hematoxylin and eosin staining. Furthermore, cytokine expression in intestinal tissues was measured by ELISA and reverse transcription-quantitative PCR. Antioxidative activities were assessed by determining the levels of reactive oxygen species (ROS), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA). Apoptosis was detected by flow cytometry. Apoptosis-related proteins, toll-like receptor 4 (TLR4) protein and NF-κB translocation were examined by western blotting. Immunohistochemical staining was used to observe TLR4 and NF-κB p65 expression in intestinal tissues. The present study suggested that loganin administration significantly reduced burn injury-induced intestinal histological changes, tumor necrosis factor-α, interleukin (IL)-6 and IL-1β production and oxidative stress, evidenced by decreased ROS levels and MDA content (P<0.05). Furthermore, loganin increased SOD, CAT and GSH-Px levels and intestinal epithelial cell apoptosis. Loganin treatment also significantly inhibited activation of the TLR4/NF-κB signaling pathway in the intestine of severely burned rats (P<0.05). In conclusion, loganin reduced burns-induced intestinal inflammation and oxidative stress, potentially by regulating the TLR4/NF-κB signaling pathway.

Keywords: TLR4/NF-κB signaling pathway; burns; intestinal inflammation; loganin; oxidative stress.

Copyright © 2020, Spandidos Publications.

5 figures
full-text links
Proceed to details Cite
 Share
15
Exp Ther Med
. 2020 Jul;20(1):454-460. doi: 10.3892/etm.2020.8730. Epub 2020 May 7.
Combination of Sufentanil, Dexmedetomidine and Ropivacaine to Improve Epidural Labor Analgesia Effect: A Randomized Controlled Trial
Gehui Li 1, Yuci Xiao 1, Xiaofei Qi 1, Hao Wang 2, Xiaoguang Wang 1, Jing Sun 1, Yong Li 1, Yuantao Li 1
Affiliations expand
PMID: 32537010 PMCID: PMC7282115 DOI: 10.3892/etm.2020.8730
Free PMC article
Abstract
Opioids and α2-agonists have been used as epidural adjuvants in local anesthetics for a long time, but the effect of the combination of opioids and α2-agonists as epidural adjuvants is not completely understood. In the present study, the combination of dexmedetomidine (Dex) and sufentanil as adjuvants to ropivacaine for epidural labor analgesia was investigated. A total of 108 parturient women receiving labor epidural analgesia were randomly divided into three groups: i) Group RD received 0.1% ropivacaine + 0.5 µg/ml Dex; ii) Group RS received 0.1% ropivacaine + 0.5 µg/ml sufentanil; and iv) Group RDS received 0.1% ropivacaine + 0.25 µg/ml Dex + 0.25 µg/ml sufentanil. Patients received a 10 ml loading dose followed by a maintenance by patient controlled epidural analgesia. The visual analog scale scores, onset time, local anesthetic requirements, motor blockage and adverse effects were recorded. Group RDS displayed an improved labor analgesia effect compared with Groups RD and RS. Group RDS displayed a shorter onset time compared with Groups RD and RS, and a reduced local anesthetic requirement compared with Group RS. The motor blockage in Groups RDS and RS was significantly lower compared with Group RD, and the incidence of pruritus in Groups RDS and RD was lower compared with Group RS. In conclusion, the combined use of 0.25 µg/ml Dex and 0.25 µg/ml sufentanil as adjuvants to 0.1% ropivacaine for epidural labor analgesia displayed an improved analgesia effect compared with the use of either 0.5 µg/ml sufentanil or 0.5 µg/ml Dex alone. The present study was registered with the Chinese Clinical Trial Registry Center on 23 February, 2018 (registration no. ChiCTR-IOR-1800014943).

Keywords: anesthesia; dexmedetomidine; epidural; labor pain; sufentanil.

Copyright: © Li et al.

39 references2 figures
full-text links
Proceed to details Cite
 Share
16
Exp Ther Med
. 2020 Jul;20(1):561-571. doi: 10.3892/etm.2020.8693. Epub 2020 Apr 29.
Cardiovascular Magnetic Resonance Clarifies Arrhythmogenicity in Asymptomatic Young Athletes With Ventricular Arrhythmias Undergoing Pre-Participation Evaluation
George Markousis-Mavrogenis 1, Aikaterini Giannakopoulou 2, Nikolaos Andreou 2, George Papadopoulos 2, Vasiliki Vartela 1, Genovefa Kolovou 1, Flora Bacopoulou 3, Konstantinos Tsarouhas 3 4, Christina Kanaka-Gantenbein 3, Demetrios A Spandidos 5, Sophie I Mavrogeni 1 3
Affiliations expand
PMID: 32537014 PMCID: PMC7282016 DOI: 10.3892/etm.2020.8693
Free PMC article
Abstract
Pre-participation sports examination (PPE) is a frequent reason for consultation. However, the exact role of cardiovascular magnetic resonance (CMR) in PPE remains undefined. The additive value of CMR in adolescent athletes with ventricular rhythm disturbances (VRDs) was investigated. We prospectively recruited and evaluated with CMR 50 consecutive, asymptomatic young athletes referred to our tertiary center after identification of VRDs on electrocardiogram (ECG) with otherwise normal standard PPE and echocardiography, and 20 age- and sex-matched healthy volunteer athletes who underwent the same evaluations. The primary outcome was case-control status and the secondary outcome was the discrimination between athletes with VRDs with and without non-sustained ventricular tachycardia (VT). CMR identified arrhythmogenic substrates in all athletes with VRDs. The predominant condition was myocarditis and arrhythmogenic right ventricular cardiomyopathy in patients with and without VT, respectively. Based on penalized regression analysis, late gadolinium enhancement (LGE), early gadolinium enhancement (EGE), extracellular volume fraction (ECV), and T2-mapping, best distinguished between case-control status. The aforementioned indices predicted case-control status independent of age and sex: EGE [Odds ratio (95% confidence interval): 6.89 (2.19-21.62) per 0.5-unit, P<0.001], LGE (perfect prediction), ECV [1.66 (1.25-2.22), P<0.001] and T2 mapping [1.40 (1.13-1.72), P=0.002], among other independent CMR-derived predictors. Only indexed ventricular volumes independently discriminated between VRD patients with and without VT. In this study, asymptomatic young athletes with VRDs and normal PPE/echocardiography were optimally discriminated from healthy control athletes by CMR-derived indices, and CMR allowed for the identification of arrhythmogenic substrates in all cases.

Keywords: athlete; cardiovascular magnetic resonance; penalized regression; pre-participation sports evaluation; sudden cardiac death; ventricular arrhythmia.

Copyright: © Markousis-Mavrogenis et al.

40 references
full-text links
Proceed to details Cite
 Share
17
Exp Ther Med
. 2020 Jul;20(1):359-366. doi: 10.3892/etm.2020.8708. Epub 2020 Apr 30.
Molecular Hydrogen Improves Type 2 Diabetes Through Inhibiting Oxidative Stress
Yi Ming 1, Qi-Hang Ma 1, Xin-Li Han 2, Hong-Yan Li 1
Affiliations expand
PMID: 32537002 PMCID: PMC7291681 DOI: 10.3892/etm.2020.8708
Free PMC article
Abstract
The aim of the present study was to investigate the potential therapeutic effects of molecular hydrogen on type 2 diabetes mellitus (T2DM) in rats. Following maintenance on a high-fat diet for 4 weeks, a T2DM model was established using an injection of 30 mg/kg streptozotocin via the caudal vein into Sprague-Dawley rats. On day 0 and Day 80, the blood samples were obtained from each rat for the measurement of biochemical indicators including blood lipids, fasting blood glucose, hepatic glycogen, fasting serum insulin, insulin sensitivity index, insulin resistance index, serum superoxide dismutase (SOD) and serum malondialdehyde (MDA) using an automatic biochemical analyzer. The kidneys and pancreas tissues were harvested for HE staining and Western blot assay of toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), phosphorylated (p)-p65, p65, p-IκB and IκB. The results showed that in rats with T2DM, molecular hydrogen treatment decreased fasting blood glucose levels, increased hepatic glycogen synthesis and improved insulin sensitivity. Treatment with molecular hydrogen also increased the production of SOD whilst decreasing the production of MDA. In addition, molecular hydrogen alleviated the pathological changes exhibited by pancreatic islets and kidney during T2DM. Mechanistically, molecular hydrogen decreased TLR4 and MyD88 expression levels whilst also decreasing p65 and NF-κB inhibitor phosphorylation. In conclusion, molecular hydrogen exerted therapeutic effects against T2DM by improving hyperglycemia and inhibiting oxidative stress through mechanisms that are associated with the TLR4/MyD88/NF-κB signaling pathway.

Keywords: hyperglycemia; molecular hydrogen; oxidative stress; type 2 diabetes.

Copyright: © Ming et al.

33 references4 figures
full-text links
Proceed to details Cite
 Share
18
Exp Ther Med
. 2020 Jul;20(1):351-358. doi: 10.3892/etm.2020.8709. Epub 2020 Apr 30.
Efficacy of Recombinant Human Soluble Thrombomodulin for Acute Exacerbation of Idiopathic Pulmonary Fibrosis: A Systematic Review and Meta-Analysis
Baojun Wang 1, Ting Li 2
Affiliations expand
PMID: 32537001 PMCID: PMC7282169 DOI: 10.3892/etm.2020.8709
Free PMC article
Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing lung disease of unknown etiology. Recombinant human soluble thrombomodulin (rhTM) is used for the management of acute exacerbation (AE) of IPF. The present review aimed to summarize the evidence and perform a meta-analysis of the efficacy and safety of rhTM in the management of AE-IPF. An electronic search of titles and abstracts published until 31st August 2019 was performed in the PubMed, Biomed Central, Scopus and Embase databases. Studies comparing rhTM-treated and control subjects with AE-IPF and assessing mortality and adverse events were included. Six studies met the inclusion criteria. A total of 145 patients received rhTM, while 146 patients served as controls. The meta-analysis indicated that rhTM resulted in a reduction in 28-day [odds ratio (OR), 0.25; 95% CI, 0.08-0.77; P=0.02; I2=0%] and 90-day mortality (OR, 0.29; 95% CI, 0.17-0.49; P<0.00001; I2=0%) compared with the controls. Adverse events were pooled and no difference was determined between rhTM and control groups (OR, 1.07; 95% CI, 0.45-2.51; P=0.88; I2=0%). It was indicated that administration of rhTM may reduce the short-term mortality in patients with AE-IPF; however, the quality of evidence was not high. The drug appears to be safe without any enhanced risk of adverse events, although high-quality randomized controlled trials with a large sample size are required to further support its use in the treatment of IPF.

Keywords: acute exacerbation; adverse events; pulmonary fibrosis; survival; thrombomodulin.

Copyright: © Wang et al.

32 references4 figures
full-text links
Proceed to details Cite
 Share
19
Exp Ther Med
. 2020 Jul;20(1):293-300. doi: 10.3892/etm.2020.8690. Epub 2020 Apr 27.
A Mid-Pregnancy Risk Prediction Model for Gestational Diabetes Mellitus Based on the Maternal Status in Combination With Ultrasound and Serological Findings
Ya-Zhong Zhang 1, Lei Zhou 1, Luobing Tian 1, Xin Li 2, Guyue Zhang 1, Jiang-Yuan Qin 1, Dan-Dan Zhang 1, Hui Fang 1
Affiliations expand
PMID: 32536997 PMCID: PMC7282073 DOI: 10.3892/etm.2020.8690
Free PMC article
Abstract
Although previous studies have proposed predictive models of gestational diabetes mellitus (GDM) based on maternal status, they do not always provide reliable results. The present study aimed to create a novel model that included ultrasound data of maternal fat distribution and serum inflammatory factors. The clinical data of 1,158 pregnant women treated at Tangshan Gongren Hospital and eight other flagship hospitals in Tangshan, including the First Hospital of Tangshan Gongren Hospital group, Ninth Hospital of Tangshan Gongren Hospital group, Tangshan Gongren Hospital group rehabilitation hospital, Tangshan railway central hospital, Tangshan Gongren Hospital group Fengnan hospital, Tangshan Gongren Hospital group Qianan Yanshan hospital, Tangshan Gongren Hospital group Qianxi Kangli hospital and Tangshan Gongren Hospital group Jidong Sub-hospital, were analyzed following the division of subjects into GDM and non-GDM groups according to their diagnostic results at 24-28 weeks of pregnancy. Univariate analysis was performed to investigate the significance of the maternal clinical parameters for GDM diagnosis and a GDM prediction model was established using stepwise regression analysis. The predictive value of the model was evaluated using a Homer-Lemeshow goodness-of-fit test and a receiver operating characteristic curve (ROC). The model demonstrated that age, pre-pregnancy body mass index, a family history of diabetes mellitus, polycystic ovary syndrome, a history of GDM, high systolic pressures, glycosylated hemoglobin levels, triglyceride levels, total cholesterol levels, low-density lipoprotein cholesterol levels, serum hypersensitive C-reactive protein, increased subcutaneous fat thickness and visceral fat thickness were all correlated with an increased GDM risk (all P<0.01). The area under the curve value was 0.911 (95% CI, 0.893-0.930). Overall, the results indicated that the current model, which included ultrasound and serological data, may be a more effective predictor of GDM compared with other single predictor models. In conclusion, the present study developed a tool to determine the risk of GDM in pregnant women during the second trimester. This prediction model, based on various risk factors, demonstrated a high predictive value for the GDM occurrence in pregnant women in China and may prove useful in guiding future clinical practice.

Keywords: gestational diabetes mellitus; risk factors; risk prediction model.

Copyright: © Zhang et al.

43 references2 figures
full-text links
Proceed to details Cite
 Share
20
Exp Ther Med
. 2020 Jul;20(1):436-446. doi: 10.3892/etm.2020.8726. Epub 2020 May 7.
Expression of Eukaryotic Translation Initiation Factor 3 Subunit B in Liver Cancer and Its Prognostic Significance
Qing Yue 1, Lingyu Meng 2, Baoxing Jia 2, Wei Han 2
Affiliations expand
PMID: 32537008 PMCID: PMC7282191 DOI: 10.3892/etm.2020.8726
Free PMC article
Abstract
Liver cancer is one of the major malignancies with the worst prognosis among all solid tumor types. It is therefore ponderable to explore prognostic biomarkers and therapeutic targets for liver cancer. Eukaryotic translation initiation factor 3 subunit B (EIF3B) is closely linked to the transcription initiation of cancer-associated genes. In the present study, EIF3B was indicated to be a potential prognostic biomarker of liver cancer. The mRNA expression level of EIF3B in liver cancer was assessed by analyzing the Cancer Genome Atlas dataset. χ2 and Fisher's exact tests were used to assess the association of EIF3B expression with clinical parameters. Receiver-operating characteristic curve analysis was used for evaluating the diagnostic value of EIF3B. Overall and relapse-free survival were assessed using Kaplan-Meier curves to determine the association between EIF3B expression and survival. Univariate and multivariate Cox regression analysis were performed to identify the factors affecting overall/relapse-free survival. Gene set enrichment analysis (GSEA) was used to identify signaling pathways associated with EIF3B in liver cancer. It was revealed that EIF3B was highly expressed in liver cancer tissues and it had a promising diagnostic ability. Furthermore, the survival analysis indicated that patients with high EIF3B expression generally had shorter overall as well as relapse-free survival. Univariate and multivariate Cox analysis suggested that high EIF3B mRNA expression may serve as an independent biomarker for the prognostication of patients with liver cancer. GSEA suggested that MYC-V1 (HALLMARK_MYC_TARGETS_V1 geneset; P=0.009), MYC-V2 (HALLMARK_MYC_TARGETS_V2 geneset; P=0.004) and DNA repair pathways (HALLMARK_DNA_REPAIR geneset; P<0.001) were differentially enriched in high EIF3B expression and low EIF3B expression groups. In conclusion, high EIF3B expression was indicated to be an independent prognostic biomarker for patients with liver cancer.

Keywords: The Cancer Genome Atlas; biomarker; eukaryotic translation initiation factor 3 subunit B; liver cancer; prognosis.

Copyright: © Yue et al.

43 references5 figures
full-text links
Proceed to details Cite
 Share
21
Exp Ther Med
. 2020 Jul;20(1):395-400. doi: 10.3892/etm.2020.8724. Epub 2020 May 7.
Treatment of a Giant Complicated Distal Posterior Inferior Cerebellar Artery Aneurysm: A Case Report and Literature Review
Jun Zhu 1, Lin Yin 2, Yanjun Che 1, Zhao Liu 1, Xin Qi 1, Ke Zhou 1, Bao Zheng 1, Enyu Pan 1, Junhui Chen 3 4
Affiliations expand
PMID: 32537003 PMCID: PMC7281963 DOI: 10.3892/etm.2020.8724
Free PMC article
Abstract
Giant intracranial aneurysms, especially giant aneurysms of the distal posterior inferior cerebellar artery (PICA), remain the most difficult and challenging cerebrovascular lesions for neurosurgeons to treat. The morbidity and mortality rates of microsurgical clipping are relatively high, and endovascular embolization is also associated with many complications. In the present report, the case of a 46-year-old female patient who presented with headache and dizziness for 3 years, which was aggravated and combined with limb weakness for 1 day, is presented. A CT scan showed a lesion occupying the fourth ventricle, with slight bleeding. A MR scan also revealed a lesion occupying the fourth ventricle and compressing the brainstem, and there was distortion of the cisterns around the brainstem. CT angiography examination showed a giant irregular aneurysm located in the PICA. After evaluation, the PICA aneurysm was removed, and the PICA was clipped via a microsurgical technique without ischemia or neurological sequelae. Long-term follow-up demonstrated that the symptoms of headache and dizziness disappeared without relapse. Based on a review of the literature, this method may represent an alternative strategy for the treatment of giant PICA aneurysms, especially for aneurysms not suitable for direct clipping or endovascular embolization.

Keywords: clipping; giant aneurysm; posterior inferior cerebellar artery.

Copyright: © Zhu et al.

24 references7 figures
full-text links
Proceed to details Cite
 Share
22
Exp Ther Med
. 2020 Jul;20(1):530-542. doi: 10.3892/etm.2020.8711. Epub 2020 May 4.
gga-microRNA-375 Negatively Regulates the Cell Cycle and Proliferation by Targeting Yes-associated Protein 1 in DF-1 Cells
Xinheng Zhang 1 2 3, Zhihong Liao 1 3, Yu Wu 1 3, Yiming Yan 1 3, Sheng Chen 1 3, Shaoli Lin 4, Feng Chen 1 2 3, Qingmei Xie 1 2 3
Affiliations expand
PMID: 32537011 PMCID: PMC7281959 DOI: 10.3892/etm.2020.8711
Free PMC article
Abstract
MicroRNAs (miRNAs/miRs) serve a key role in regulating the cell cycle and inducing tumorigenesis. Subgroup J of the avian leukosis virus (ALV-J) belongs to the family Retroviridae, subfamily Orthoretrovirinae and genus Alpharetrovirus that causes tumors in susceptible chickens. gga-miR-375 is downregulated and Yes-associated protein 1 (YAP1) is upregulated in ALV-J-induced tumors in the livers of chickens, and it has been further identified that YAP1 is the direct target gene of gga-miR-375. In the present study, it was found that ALV-J infection promoted the cell cycle and proliferation in DF-1 cells. As the cell cycle and cell proliferation are closely associated with tumorigenesis, further experiments were performed to determine whether gga-miR-375 and YAP1 were involved in these cellular processes. It was demonstrated that gga-miR-375 significantly inhibited the cell cycle by inhibiting G1 to S/G2 stage transition and decreasing cell proliferation, while YAP1 significantly promoted the cell cycle and proliferation. Furthermore, these cellular processes in DF-1 cells were affected by gga-miR-375 through the targeting of YAP1. Collectively, the present results suggested that gga-miR-375, downregulated by ALV-J infection, negatively regulated the cell cycle and proliferation via the targeting of YAP1.

Keywords: Yes-associated protein 1; avian leukosis virus; cell cycle; cell proliferation; gga-microRNA-375.

Copyright: © Zhang et al.

54 references6 figures
full-text links
Proceed to details Cite
 Share
23
Exp Ther Med
. 2020 Jul;20(1):343-350. doi: 10.3892/etm.2020.8706. Epub 2020 Apr 30.
Downregulation of DEC1 by RNA Interference Attenuates ischemia/reperfusion-induced Myocardial Inflammation by Inhibiting the TLR4/NF-κB Signaling Pathway
Weipan Xu 1, Kai Zhang 1, Yi Zhang 1, Shanxue Ma 1, Daoqun Jin 1
Affiliations expand
PMID: 32537000 PMCID: PMC7282085 DOI: 10.3892/etm.2020.8706
Free PMC article
Abstract
Inflammation has been implicated in the pathogenesis of myocardial ischemia/reperfusion (I/R) injury (MIRI). Previous studies have confirmed that deleted in esophageal cancer 1 (DEC1) is an important transcription factor in inflammation. However, the role of DEC1 in MIRI remains unclear. The present study aimed to determine whether the downregulation of DEC1 by RNA interference alleviated inflammation to protect against MIRI. Adult Sprague-Dawley rats (n=48) were randomly divided into four groups: Sham; I/R; adenovirus expressing green fluorescent protein control (Ad-G-Control); and DEC1-targeting RNA interference (Ad-G-DEC1) groups. Following gene delivery 4 days later, the rat myocardial I/R model was established and myocardial enzymes [creatine kinase (CK) and lactate dehydrogenase (LDH)] were detected. Hematoxylin and eosin (H&E) staining was performed to evaluate the myocardial damage and the infarct area was assessed using Evans Blue/triphenyltetrazolium chloride staining. The inflammatory mediators interleukin (IL)-β and tumor necrosis factor (TNF)-α were also detected using ELISA kits to assess the inflammatory response. Finally, western blotting and reverse transcription-quantitative PCR were used to analyze the expression levels of associated proteins and mRNAs. Ad-G-DEC1 RNA interference markedly decreased DEC1 expression levels. In addition, following the downregulation of DEC1 expression, the infarct size, CK, LDH, Toll-like receptor (TLR)4, NF-κB, IL-β and TNF-α levels were all significantly decreased. In conclusion, the results of the present study suggested that the downregulation of DEC1 may decrease the inflammation by suppressing the TLR4/NF-κB signaling pathway, which may represent a therapeutic target for MIRI.

Keywords: RNA interference; Toll-like receptor 4/NF-κB; deleted in esophageal cancer 1; inflammation; myocardial ischemia/reperfusion injury.

Copyright: © Xu et al.

34 references6 figures
full-text links
Proceed to details Cite
 Share
24
Exp Ther Med
. 2020 Jul;20(1):581-590. doi: 10.3892/etm.2020.8718. Epub 2020 May 6.
Baicalin Alleviates TNBS-induced Colitis by Inhibiting PI3K/AKT Pathway Activation
Lei Zhu 1, Hong Shen 1, Pei-Qing Gu 1, Ya-Jun Liu 1, Lu Zhang 1, Jia-Fei Cheng 1
Affiliations expand
PMID: 32537016 PMCID: PMC7281943 DOI: 10.3892/etm.2020.8718
Free PMC article
Abstract
Inflammatory bowel diseases (IBDs) are chronic immunological disorders of the intestinal tract characterized by persistent inflammation. Baicalin, a type of flavonoid, has exhibited a wide range of pharmacological activities, including immunomodulation and anti-inflammation. However, little is known about the therapeutic role of baicalin in IBD. The aim of the present study was to ascertain whether baicalin could be a therapeutic drug of IBD and investigate its specific mechanisms. In the present study, the results revealed that baicalin not only significantly alleviated TNBS-induced colitis by reducing the release of IL-6, TNF-α and IL-1β and increasing the level of IL-10, but promoted the expression of tight-junction proteins ZO-1 and β-catenin, which may have been achieved by blockage of the PI3K/AKT signaling pathway. In vitro, the results demonstrated that baicalin clearly inhibited the release of TNF-α, IL-6 and IL-1β and promoted the expression of IL-10 in LPS-induced HT-29 cells, and significantly decreased LPS-induced HT-29 cell apoptosis by blockage of the PI3K/AKT signaling pathway. In conclusion, the present research revealed for the first time that baicalin acted as a therapeutic drug in IBD by suppression of the PI3K/AKT signaling pathway.

Keywords: LPS; PI3K/AKT; TNBS; baicalin; inflammatory bowel diseases.

Copyright © 2020, Spandidos Publications.

5 figures
full-text links
Proceed to details Cite
 Share
25
Exp Ther Med
. 2020 Jul;20(1):447-453. doi: 10.3892/etm.2020.8729. Epub 2020 May 7.
Identifying Compositional and Structural Changes in the Nucleus Pulposus From Patients With Lumbar Disc Herniation Using Raman Spectroscopy
Xuehui Wang 1 2, Jianfang Meng 3, Tongxing Zhang 4, William Weijia Lv 5, Zhao Liang 6, Qian Shi 1, Zhaoyang Li 3, Tao Zhang 2
Affiliations expand
PMID: 32537009 PMCID: PMC7281961 DOI: 10.3892/etm.2020.8729
Free PMC article
Abstract
Lower back pain (LBP) is one of the most common musculoskeletal complaints worldwide. Intervertebral disc degeneration (IDD) is considered to be a significant contributor to LBP; however, the mechanisms underlying IDD remain to be fully elucidated. One of the major features of IDD is the decreased content of type II collagen and proteoglycans in the nucleus pulposus (NP). The present study aimed to investigate the biochemical mechanisms of IDD at the microscopic level using Raman spectroscopy. Raman spectroscopy, based on inelastic scattering of light, is an emerging optical technique that may measure the chemical composition of complex biological samples, including biofluids, cells and tissues. In the present study, 30 NP tissue samples from 30 patients who were diagnosed with lumbar disc herniation and received spinal fusion surgery to relieve LBP were obtained and analyzed. Routine pre-operative 3.0T, T2-weighed MRI was used to classify the cases according to Pfirrmann grades and the T2 signal intensity value of the NP was measured. Subsequently, all NP samples were scanned and analyzed using a Laser MicroRaman Spectrometer at room temperature. The Raman spectral results demonstrated that the relative content of proteoglycans, expressed as the relative intensity ratio of two peaks (I1064/I1004), was significantly inversely correlated with the Pfirrmann grade (ρ=-0.6462; P<0.0001), whereas the content of collagen (amide I) was significantly positively correlated with the Pfirrmann grade (ρ=0.5141; P<0.01). In conclusion, the higher relative intensity of the ratio of two peaks (I1670/I1640; Amide I) represented a higher fractional content of disordered collagen, which suggested that the defective collagen structure may lead to NP abnormalities.

Keywords: Raman spectroscopy; lumbar disc herniation; magnetic resonance imaging; nucleus pulposus.

Copyright: © Wang et al.

36 references3 figures
full-text links
Proceed to details Cite
 Share
26
Exp Ther Med
. 2020 Jul;20(1):211-218. doi: 10.3892/etm.2020.8721. Epub 2020 May 6.
Value of S100A12 in Predicting In-Stent Restenosis in Patients With Coronary Drug-Eluting Stent Implantation
Hengyi Liang 1, Yuqi Cui 1 2, Haoran Bu 1, Hang Liu 3, Pengcheng Yan 1, Lianqun Cui 1, Liming Chen 1
Affiliations expand
PMID: 32536993 PMCID: PMC7282035 DOI: 10.3892/etm.2020.8721
Free PMC article
Abstract
In-stent restenosis (ISR) after drug-eluting stent (DES) placement has recently emerged as a major concern for cardiologists. Identification of biomarkers to predict ISR may be invaluable for tailored management strategies. The present study aimed to evaluate the prognostic utility of circulating S100 calcium-binding protein A12 (S100A12) for ISR. Out of 2,443 patients with DES-based percutaneous coronary intervention (PCI) and follow-up angiography at ~1 year after DES-based PCI, 258 patients were diagnosed with ISR and 258 patients without ISR were randomly selected as controls. Serum S100A12 levels were determined in the two subsets on admission. The association between ISR and the circulating levels of S100A12 was determined by constructing two multivariate stepwise logistic regression models. In addition, S100A12 was assessed for its ability to predict ISR using receiver operating characteristic (ROC) curve analysis. The serum levels of S100A12 at baseline were significantly elevated in patients in the ISR group compared with those in the non-ISR group (P<0.001). In the multivariate logistic regression analysis, after adjusting for conventional cardiovascular risk factors, laboratory parameters and medication after the procedure, the S100A12 level was revealed to be independently associated with ISR. When a cut-off for serum S100A12 levels of 34.75 ng/ml was used, the ROC curve was able to predict ISR with 72.8% sensitivity and 79.1% specificity, and the area under the ROC curve was 0.796 (95% CI: 0.757 to 0.834, P<0.001). Furthermore, addition of S100A12 to established risk factors significantly improved the predictive power of reference models for ISR. S100A12 may serve as an independent marker to predict ISR in patients undergoing coronary DES implantation.

Keywords: S100 calcium-binding protein A12; drug-eluting stent; in-stent restenosis; inflammation; percutaneous coronary intervention.

Copyright: © Liang et al.

34 references4 figures
full-text links
Proceed to details Cite
 Share
27
Exp Ther Med
. 2020 Jul;20(1):301-308. doi: 10.3892/etm.2020.8695. Epub 2020 Apr 29.
Effectiveness of Digital PCR for MYD88 L265P Detection in Vitreous Fluid for Primary Central Nervous System Lymphoma Diagnosis
Kun Chen 1, Yanchun Ma 1, Tianling Ding 2, Xinju Zhang 3, Bobin Chen 2, Ming Guan 1 3
Affiliations expand
PMID: 32536998 PMCID: PMC7282034 DOI: 10.3892/etm.2020.8695
Free PMC article
Abstract
Primary central nervous system lymphoma (PCNSL) is a rare type of primary extranodal lymphoma (PEL). MYD88L265P mutation has been observed in up to 75% of PCNSL cases, however, the validity and sensitivity of digital PCR in detecting this mutation remains to be elucidated. A total of 44 PCNSL patients, 15 diffuse large B-cell lymphoma not otherwise specified (DLBCL-NOS) patients and 13 other PEL patients were enrolled in the present study. The abilities of reverse transcription quantitative PCR (RT-qPCR) and droplet digital PCR (ddPCR) to detect the MYD88L265P mutation in cerebral spinal fluid (CSF) samples were compared. The results suggested that ddPCR showed superior mutation detection sensitivity when compared with RT-qPCR (58 vs. 15%; P<0.05). The MYD88L265P mutation was significantly associated with increased MYD88 protein overexpression in PCNSL brain tissue samples (P<0.05). Analysis of MYD88L265P mutation status in CSF and vitreous fluid samples using ddPCR may be a promising technique for minimally invasive confirmation of PCNSL diagnosis.

Keywords: MYD88L265P mutation; central nervous system lymphoma; cerebrospinal fluid; ddPCR; vitreous aspirates.

Copyright: © Chen et al.

48 references4 figures
full-text links
Proceed to details Cite
 Share
28
Exp Ther Med
. 2020 Jul;20(1):572-580. doi: 10.3892/etm.2020.8727. Epub 2020 May 7.
MicroRNA-513a-3p Regulates Colorectal Cancer Cell Metabolism via Targeting Hexokinase 2
Chen Li 1, Zhijin Yu 2, Jinpeng Ye 1
Affiliations expand
PMID: 32537015 PMCID: PMC7282190 DOI: 10.3892/etm.2020.8727
Free PMC article
Abstract
Disruption of cell metabolism is a hallmark of cancer cells. Accumulating evidence suggests that microRNAs (miRNAs/miRs) are involved in almost all physiological and pathological processes. The aberrant expression of miRNAs induces metabolic reprogramming in cancer cells and thus, promotes proliferation. In the current study, miR-513a-3p was identified as a significantly downregulated miRNA in colorectal cancer cells and tumors. Overexpression of miR-513a-3p in colorectal cancer cells inhibited proliferation and glycolysis. A well-documented metabolic regulator, hexokinase 2 (HK2), was predicted and validated HK2to be a target gene of miR-513a-3p in colorectal cancer cells. In addition, overexpression of HK2 reversed the miR-513a-3p mimic-induced inhibition of proliferation. The association between HK2 and miR-513a-3p was further observed in tumors collected from patients with colorectal cancer. The findings suggest that miR-513a-5p may inhibit glycolysis in colorectal cancer cells via repressing HK2 expression, indicating that miR-513a-5p may be a tumor suppressor in colorectal cancer.

Keywords: colorectal cancer; hexokinase 2; microRNA-513a-3p.

Copyright © 2020, Spandidos Publications.

7 figures
full-text links
Proceed to details Cite
 Share
29
Exp Ther Med
. 2020 Jul;20(1):623-629. doi: 10.3892/etm.2020.8717. Epub 2020 May 6.
Biallelic Mutations in Carbamoyl Phosphate Synthetase 1 Induced Hyperammonemia in a Neonate: A Case Report
Jun Xu 1, Aimin Zhang 1, Furong Huang 1
Affiliations expand
PMID: 32537019 PMCID: PMC7282193 DOI: 10.3892/etm.2020.8717
Free PMC article
Abstract
The aim of the present report was to describe the clinical presentation, diagnosis, and treatment of a case of carbamoyl phosphate synthetase 1 (CPS1) deficiency in a neonate, specifically, a 3 day-old female who visited Hunan Provincial People's Hospital due to anorexia and lethargy for 1 day. Physical and laboratory examination, and MRI were undertaken. Whole exome sequencing (WES) was applied for molecular etiology identification. Sanger sequencing was utilized to validate the variants detected by WES. Structural modeling was conducted for pathogenic analysis. Clinical examination revealed increased intracranial pressure, hyperammonemia, reduced citrulline, and increased glutamic acid levels. WES identified compound heterozygosity of c.713G>C, p.Arg238Pro and c.2339G>A, p.Arg780His in CPS1 (NCBI reference sequence, NM_001875.4) as candidate pathogenic variants. Sanger sequencing validated these variants. Structural modeling further confirmed the pathogenesis of these mutations. In conclusion, CPS1 deficiency in neonates is a serious condition that may be misdiagnosed due to severe infection. WES can be a helpful tool in facilitating the diagnosis of this disease.

Keywords: carbamoyl phosphate synthetase 1; hyperammonemia; urea cycle disorders.

Copyright © 2020, Spandidos Publications.

3 figures
full-text links
Proceed to details Cite
 Share
30
Exp Ther Med
. 2020 Jul;20(1):219-226. doi: 10.3892/etm.2020.8716. Epub 2020 May 5.
Comparison of Rapamycin and Methylprednisolone for Treating Inflammatory Muscle Disease in a Murine Model of Experimental Autoimmune Myositis
Juan Kang 1, Dongyun Feng 1, Feng Yang 1, Xiaojia Tian 1, Wenjuan Han 1, Hongge Jia 1 2
Affiliations expand
PMID: 32536994 PMCID: PMC7291653 DOI: 10.3892/etm.2020.8716
Free PMC article
Abstract
Idiopathic inflammatory myopathies (IIMs) are a group of autoimmune inflammatory muscle diseases. Rapamycin has been shown to ameliorate inflammation and improve muscle function in a mouse model of experimental autoimmune myositis (EAM). In the present study, the therapeutic effect of rapamycin was compared with methylprednisolone (MP) on EAM. Mice were injected with myosin for 10 days to induce EAM and were subsequently treated with rapamycin (1.5 mg/kg), MP (40 mg/kg) or placebo (DMSO) for 14 days. The rapamycin-treated group exhibited significantly decreased severe inflammation and improved muscle strength compared with the MP-treated group. The plasma transforming growth factor-β (TGF-β) concentration in the rapamycin-treated group was significantly higher compared with the placebo group. However, both treatment groups exhibited significantly lower plasma interleukin-10 levels compared with the placebo group. Moreover, splenic regulatory T cell frequency in both the rapamycin- and MP-treated animals was significantly lower than that in the animals of the placebo group. Rapamycin showed better immune suppressive effects than MP in this model of EAM, and these effects were likely to be mediated by the TGF-β signaling pathway.

Keywords: EAM; IIMs; TGF-β; Treg cells; rapamycin.

Copyright: © Kang et al.

49 references4 figures
full-text links
Proceed to details Cite
 Share
31
Editorial Exp Ther Med
. 2020 Jul;20(1):9-11. doi: 10.3892/etm.2020.8712. Epub 2020 May 4.
Tackling Key Immunological and Immuno-Dermatological Pathways and Their Link to Treatment Options
Daniel Boda 1 2
Affiliations expand
PMID: 32536987 PMCID: PMC7282104 DOI: 10.3892/etm.2020.8712
Free PMC article
Abstract
No abstract available
Keywords: hidradenitis suppurativa; irritable bowel syndrome; psoriasis; pyoderma gangrenosum; skin immunology.

21 references
supplementary info
Publication typesexpand
full-text links
Proceed to details Cite
 Share
32
Exp Ther Med
. 2020 Jul;20(1):147-150. doi: 10.3892/etm.2020.8692. Epub 2020 Apr 28.
[Comment] Treatment Strategies to Fight the New Coronavirus SARS-CoV-2: A Challenge for a Rubik's Cube Solver
Eliza Tsitoura 1, Eleni Bibaki 1, Maria Bolaki 1, Eirini Vasarmidi 1, Athina Trachalaki 2, Emmanouil K Symvoulakis 3, Demetrios A Spandidos 4, Katerina M Antoniou 1
Affiliations expand
PMID: 32536988 PMCID: PMC7282080 DOI: 10.3892/etm.2020.8692
Free PMC article
Abstract
SARS-coronavirus-2 (SARS-CoV-2), the etiologic agent of the new lung disease COVID-19 is closely related to SARS-CoV, and together with MERS-CoV are three new human coronaviruses that emerged in the last 20 years. The COVID-19 outbreak is a rapidly evolving situation with higher transmissibility and infectivity compared with SARS and MERS. Clinical presentations range from asymptomatic or mild symptoms to severe illness. The prevalent cause of mortality is pneumonia that progresses to ARDS. The ongoing pandemic has already resulted in more than 135,000 deaths and an unprecedented burden on national health systems worldwide. Pending the availability of a vaccine, there is a critical need to identify effective treatments and a number of clinical trials have been implemented worldwide. Trials are based on repurposed drugs that are already approved for other infections, have acceptable safety profiles or have performed well in animal studies against the other two deadly coronaviruses. Supportive care remains the mainstay of therapy at present, as it is still unclear how well these data can be extrapolated to SARS-CoV-2. Most of those emerging re-introduced drugs are administered to patients in the context of clinical trials. In this review, we summarize the strategies currently employed in the treatment of COVID-19.

Keywords: COVID-19; SARS-CoV-2; chloroquine; favipiravir; remdesivir; stem cell therapy; tocilizumab.

Copyright: © Tsitoura et al.

36 references
full-text links
Proceed to details Cite
 Share
33
Exp Ther Med
. 2020 Jul;20(1):205-210. doi: 10.3892/etm.2020.8707. Epub 2020 Apr 30.
Interleukin-22 Regulates Gastric Cancer Cell Proliferation Through Regulation of the JNK Signaling Pathway
Hao Dong 1, Fengming Zhu 2, Shilu Jin 3, Jing Tian 4
Affiliations expand
PMID: 32536992 PMCID: PMC7282062 DOI: 10.3892/etm.2020.8707
Free PMC article
Abstract
Inflammation is considered as one of the major hallmarks of cancer and is associated with gastric cancer. Interleukin-22 (IL-22), a member of the IL-10 family, serves an important role in inflammatory diseases and tumors. The aim of the present study was to examine the effects of IL-22 on the proliferation of gastric cancer cells (AGS cells) in vitro and explore the associated molecular mechanism. The results of a Cell Counting kit-8 assay using AGS cells transfected with an IL-22-plasmid indicated that IL-22 could promote AGS cell viability. However, when IL-22 was knocked down by IL-22-short hairpin (sh)RNA, the viability of AGS cells was significantly impaired. Western blotting results indicated that IL-22 decreased the activation of the mitogen-activated protein kinase (MAPK) signaling pathway. Furthermore, IL-22-shRNA transfection increased the activation of MAPK, as evidenced by the upregulated phosphorylation of ERK and JNK. Taken together, the results of the present study suggest that IL-22 regulated the viability of gastric cancer cells through the JNK signaling pathway, suggesting a therapeutic approach for gastric cancer via targeting IL-22.

Keywords: JNK; cell viability; gastric cancer; inflammation; interleukin-22; mitogen-activated protein kinase.

Copyright: © Dong et al.

36 references4 figures
full-text links
Proceed to details Cite
 Share
34
Exp Ther Med
. 2020 Jul;20(1):637-645. doi: 10.3892/etm.2020.8723. Epub 2020 May 6.
Promoter Hypermethylation influences the Suppressive Role of Long Non-Coding RNA MEG3 in the Development of Multiple Myeloma
Wenjun Yu 1 2, Qinglin Shi 2, Chao Wu 2, Xuxing Shen 2, Lijuan Chen 2, Jiaren Xu 1
Affiliations expand
PMID: 32537021 PMCID: PMC7281984 DOI: 10.3892/etm.2020.8723
Free PMC article
Abstract
Methylation is a fundamental regulator of gene transcription. Long non-coding RNA maternally expressed 3 (MEG3) inhibits cell proliferation in various types of cancer. However, the molecular mechanisms of MEG3 methylation in the regulation of multiple myeloma (MM) are unknown. In the present study, MEG3 upregulation was negatively associated with the International Staging System (ISS) status of the bone marrow samples of 39 patients with MM. MEG3 overexpression in an MM cell line resulted in elevated p53 expression. Furthermore, the results of methylation-specific PCR revealed that the abnormal methylation status of the MEG3 promoter region was present in eight of the 39 bone marrow samples collected. Treatment of the MM cell line with the DNA methylation inhibitor 5-Aza-2'-deoxycytidine (5-Aza-CdR) resulted in tumor cell proliferation inhibition, apoptosis induction and G0/G1 cell cycle arrest. Furthermore, 5-Aza-CdR decreased aberrant hypermethylation of the MEG3 promoter and increased the expression of MEG3. However, 5-Aza-CdR exerted no effect on p53 expression. To the best of our knowledge, the present study is the first to report that the demethylation reagent 5-Aza-CdR may serve as a therapeutic agent in MM by upregulating MEG3 expression. However, the mechanism of action was independent of p53 expression.

Keywords: long non-coding RNA; maternally expressed 3; multiple myeloma; promoter hypermethylation.

Copyright © 2020, Spandidos Publications.

5 figures
full-text links
Proceed to details Cite
 Share
35
Exp Ther Med
. 2020 Jul;20(1):401-408. doi: 10.3892/etm.2020.8732. Epub 2020 May 8.
Initial Dosage Optimization of Ciclosporin in Pediatric Chinese Patients Who Underwent Bone Marrow Transplants Based on Population Pharmacokinetics
Xiao Chen 1, Xin Yu 1, Dong-Dong Wang 1, Hong Xu 2, Zhiping Li 1
Affiliations expand
PMID: 32537004 PMCID: PMC7282146 DOI: 10.3892/etm.2020.8732
Free PMC article
Abstract
Bone marrow transplants (BMT) are an established therapeutic strategy for patients with severe aplastic anemia, acute lymphoblastic leukemia, acute myeloid leukemia or chronic myeloid leukemia. However, the successful application of BMT is limited by graft-vs.-host disease (GVHD). Ciclosporin has been widely used for treating GVHD in pediatric patients who underwent BMT. The present study aimed to optimize the dosage of ciclosporin for safety and effectiveness based on population pharmacokinetics. A non-linear mixed-effects model was used to analyze the clinical data of pediatric patients who underwent BMT between September 2016 and September 2019 at the Children's Hospital of Fudan University. Monte Carlo simulations were used to identify the optimal dose of ciclosporin. The final population pharmacokinetic model indicated that body weight and days post-transplant influenced the clearance of ciclosporin in pediatric patients who underwent BMT. The present study indicated that the optimal initial dose of ciclosporin for pediatric patients weighing 5-30 kg who underwent BMT was 6 mg/kg/day split into 2 doses.

Keywords: bone marrow transplantation; ciclosporin; initial dosage optimization; pediatric; population pharmacokinetics.

Copyright: © Chen et al.

60 references4 figures
full-text links
Proceed to details Cite
 Share