Asia Pacific Academy of Science Pte. Ltd.
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Silencing of MALAT1 Reduces Lipopolysaccharide-Induced Glomerular Endothelial Cell Damage via Mediating MiR-126-5p Expression
No full textBackground: The involvement of long non-coding RNA (lncRNA) metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in inflammation-related kidney damage has been widely demonstrated. However, the mechanisms by which MALAT1 regulate glomerular endothelial cells in sepsis remain undefined, which is the subject in this study. Methods: MALAT1-targeted gene was predicted, and verified through Starbase and dual-luciferase reporter experiment. ShMALAT1 and miR-126-5p inhibitors were transfected into lipopolysaccharide (LPS)-induced human renal glomerular endothelial cells (HRGECs) and murine glomerular endothelial cells (MGECs). The viability, reactive oxygen species (ROS) content, apoptosis and expressions of inflammatory cytokines of HRGECs and MGECs were examined by cell counting kit-8, immunofluorescence assay, flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. Expressions of vascular cellular adhesion molecule 1 (VCAM1), inter-cellular adhesion molecule-1 (ICAM-1), monocyte-chemoattractant protein-1 (MCP-1), Nuclear P65 and Cytoplasmic P65 were analyzed by Western blotting. Results: MALAT1 silencing promoted viability and Cytoplasmic P65 expression, but inhibited ROS content, apoptosis, inflammatory cytokine (TNF-α (tumor necrosis factor-alpha) and IL-6 (interleukin 6)) levels, and VCAM1, ICAM-1, MCP-1 and Nuclear P65 expressions in LPS-induced HRGECs and MGECs. MiR-126-5p had a targeted binding relationship with MALAT1 in HRGECs, and MALAT1 silencing increased miR-126-5p expression. MiR-126-5p inhibitor had the opposite effect to MALAT1 silencing, and reversed the effect of MALAT1 silencing on viability, apoptosis and inflammatory cytokines in LPS-induced HRGECs and MGECs. Moreover, miR-126-5p inhibitor increased VCAM1, ICAM-1, MCP-1 and Nuclear P65 expressions, but reduced that of Cytoplasmic P65 in LPS-induced HRGECs and MGECs, and partially offset the effect of shMALAT1 on the above protein expressions. Conclusions: MALAT1 silencing reduces LPS-induced glomerular endothelial cell damage by promoting miR-126-5p expression
Alkbh5 Relieves Trigeminal Neuralgia by Regulating p-ERK Expression
No full textObjective: To establish the action and mechanism of action of Alkbh5 on trigeminal neuralgia (TN). Methods: Infraorbital nerve-chronic compression injury (ION-CCI) rat model was established, and the expression of Alkbh5 (Alk B homolog 5) in the trigeminal ganglion of rats was detected. The study was divided into six groups, namely, the sham group, the experimental group, the injection group of Alkbh5 overexpressing adeno-associated virus (M+OE-A), the injection group of Alkbh5 overexpressing control virus (M+OE-NC (overexpressing control virus)), the injection group of Alkbh5 interfering control virus (M+sh-NC), and the injection group of Alkbh5 interfering adeno-associated virus (M+sh-A). Each group included six rats, and the mechanical pain threshold of rats in each group was detected. Western blot was used to detect the expression of ERK (extracellular signal-regulated kinase). Results: The relative expression level of Alkbh5 and the mechanical pain threshold of rats in the experimental group were significantly lower than those in the sham group 4 d, 7 d and 14 d after modeling (p < 0.05). The relative expression level of Alkbh5 in the M+OE-A group was significantly higher than that in the M+OE-NC group. The mechanical pain thresholds on days 4, 7 and 14 of modeling in the M+OE-A group were significantly higher than those in the M+OE-NC group (p < 0.05). The relative expression level of Alkbh5 in the M+sh-A group was significantly lower than that in the M+sh-NC group. The mechanical pain thresholds of the M+sh-A group were significantly lower than those of the M+sh-NC group 14 d after modeling (p < 0.05). The protein expression levels of p-ERK in the experimental group and M+OE-NC group were significantly higher than that in the sham group, and the protein expression levels of phosphorylated extracellular regulated protein kinases (p-ERK) in M+OE-A group were lower than those in the experimental group and M+OE-NC group (p < 0.05). The protein expression levels of p-ERK in the experimental group and M-sh-NC group were higher than that in the sham group, and the protein expression levels of p-ERK in the M+sh-A group were higher than those in the experimental group and M-sh-NC group (p < 0.05). Conclusions: Alkbh5 can alleviate the mechanical hyperalgesia of the trigeminal neuralgia rat model, by negatively regulating the expression of p-ERK
Research on Protective Mechanism of Antioxidant Sodium TanshinoneⅡA Sulfonate on Erectile Function in Hyperlipidemia Rats
No full textObjective: Sodium tanshinone ⅡA sulfonate (STS) is recognized to be beneficial to oxidative stress (OS). However, it is unclear whether it protects erectile function by antioxidative stress and maintains the contractile phenotype of cavernosal smooth muscle cells (CCSMCs) in hyperlipidemia-induced erectile dysfunction (ED) rats. Therefore, this research aimed to assess the protective effect and the mechanism of STS on cavernous smooth muscle cells in hyperlipidemia-related ED. Methods: This study assessed erectile function using the intracavernous pressure (ICP)/mean arterial pressure (MAP) ratio. The phenotypic and oxidative-related markers were determined using western blot and immunohistochemistry assays. Sprague-Dawley rats were grouped as a normal control (NC) and four hyperlipidemia groups, including hyperlipidemia rats (HR), hyperlipidemia with saline (HR+NS), hyperlipidemia with 300 mg/kg N-acetylcysteine (HR+NAC), and hyperlipidemia rats with 10 mg/kg sodium tanshinone ⅡA sulfonate (HR+STS). After 4 months, all rats were sacrificed for serum biochemistry, OS markers, and penile histologic examinations after ICP and MAP tests. Results: The ICP/MAP ratio was significantly higher in HR+STS and HR+NAC groups than in HR and HR+NS groups (p < 0.05). Compared to the other hyperlipidemia rats, STS treatment markedly increased the expression of phenotypic proteins alpha-smooth muscle actin (α-SMA), smooth muscle myosin heavy chain (SMMHC), calponin, and Myocardin and decreased the osteopontin (OPN) expression in the penis (p < 0.05). Furthermore, we demonstrated that STS increased SOD and GSH expression while reducing MDA expression in serum and corpus cavernosum tissues compared with the HR group. Conclusions: STS treatment protected the erectile function by reducing the OS and maintaining the contractile phenotype in the CCSMCs of the hyperlipidemia-induced ED rats
Preliminary Validation of Pictorial Representation of Illness and Self Measure-Revised 2 (PRISM-R2): An Effective Tool for Assessing Suffering of Patients with Spinal Cord Injury in Mainland China
No full textObjectives: Patients with spinal cord injury (SCI) often have different degrees of psychological distress, which is related to the injury’s suddenness and the associated high level of disability. The Pictorial Representation of Illness and Self Measure-Revised 2 (PRISM-R2) has been developed as a visual measure for assessing patients suffering from SCI. This study aimed to validate the effectiveness of PRISM-R2 in assessing the suffering of patients with SCI in Mainland China. Setting: Data were collected from hospitalized individuals with SCI at the Shanghai Yangzhi Rehabilitation Hospital (School of Medicine, Tongji University). Methods: The evaluation tools include: (1) The Pictorial Representation of Illness and Self Measure-Revised 2 (PRISM-R2), (2) the World Health Organization Quality of Life Short Form Survey (WHOQOL-BREF), (3) the Multidimensional Body-Self Relations Questionnaire (MBSRQ), (4) the Patient Health Questionnaire-9 (PHQ-9), (5) the Social Support Rating Scale (SSRS), (6) the Numerical Rating Scale (NRS) and (7) the Modified Barthel Index (MBI). The validity of the PRISM-R2 content was also tested by content analysis. Results: The Self Illness Separation (SIS) and the Illness Perception Measure (IPM) showed a strong correlation (r = –0.54;p < 0.05). Qualitative data indicated that the interpretation of the PRISM-R2 task is not only consistent among patients, but it is consistent with that expected from existing literature on suffering. As expected, PRISM-R2 showed strong correlations with psychological variables (notably depression and social support, and appearance orientation) and also correlated with WHOQOL-BREF subscale scores. Conclusions: PRISM-R2 effectively reflects the perception of psychological variables and suffering in SCI patients and it may be beneficial in evaluating or guiding the intervention for people with SCI
MiR-182-5p Regulates Chondrocyte Inflammation and Oxidative Stress to Promote Osteoarthritis through Targeting the SIRT1/Nrf2 Signaling Pathway
No full textBackground: The possible molecular mechanism and the influence of microRNA-182-5p (miR-182-5p) in the oxidative stress and inflammatory response in osteoarthritis (OA) were expected to be explored in this study. Methods: Interleukin-1β (IL-1β)-induced human chondrocytes (CHON)-001 cell line was utilized to construct in vitro OA models. Real-time quantitative polymerase chain reaction (qRT-PCR) was executed for measuring silent information regulation of transcription 1 (SIRT1) and miR-182-5p expression in clinical cartilage tissue and CHON-001 cells; enzyme-linked immuno sorbent assay (ELISA), biochemical assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to measure the levels of inflammatory factors, the levels of oxidative stress substances, and the proliferation rate in CHON-001 cells, respectively. Further, the targeting association of this miRNA with SIRT1 was identified via dual-luciferase reporter assay, and the expression of nuclear factor erythroid 2-associated factor 2 (Nrf2) signaling pathway-related protein in chondrocytes was checked via western blot. Results: Firstly, the OA model was successfully built via the stimulation of IL-1β in CHON-001 cells. The expression of that miRNA was observed to be high in IL-1β-induced chondrocyte samples and cartilage tissues of OA patients. Knocking down miR-182-5p triggered the Nrf2 signaling pathway in the chondrocytes and increased the cell proliferation, inhibited inflammation and oxidative stress. Furthermore, the dual-luciferase reporter assay and bioinfomatics analysis hinted that SIRT1 acted as a target gene of that miRNA. Besides, low SIRT1 expression was exhibited in OA tissues and the chondrocytes, and a negative association existed between SIRT1 expression and miR-182-5p expression. Knocking down SIRT1 counteracted the protective effects of miR-182-5p knockdown and the activation of Nrf2 pathway in the CHON-001 cells. Conclusions: Knocking miR-182-5p down in human chondrocytes prevented IL-1β-stimulated oxidative stress injury and cell inflammation by targetedly controlling SIRT1/Nrf2 signaling pathway, implying the potential of this miRNA serving as a target for treating OA
MicroRNA-19b-1 Up-Regulation Promotes Cell Invasion and Metastasis in Renal Cell Carcinoma
No full textBackground: Renal cell carcinoma (RCC) is a prevalent malignancy in humans of all ages worldwide. However, no identifiable risk factors have been identified in most patients, and the pathogenic mechanisms and molecular pathways of known risk factors remain unclear. Therefore, this study aimed to analyze the differentially expressed microRNAs (miRNAs) of RCC by bioinformatics and to explore their mechanism of action on RCC by in vitro experiments. Methods: ACHN and 786-O cells underwent transfection with the miR-19b-1 mimic, its inhibitor, and its negative controls. The miR-19b-1 expression level in the miRNA expression profile of RCC was analyzed using bioinformatics. The application of quantitative real-time polymerase chain reaction (qRT-PCR) was employed to examine the expression of miR-19b-1 and its transfection efficacy in RCC tissues and cells. The association between this RNA expression and survival prognosis in RCC patients was determined using the Kaplan-Meier survival curve. Transwell assay was employed to evaluate the effects of miR-19b-1 overexpression or knockout on the invasion and metastasis of ACHN and 786-O cells. Results: The expression level of miR-19b-1 was significantly elevated in RCC compared to controls (p < 0.05). The Kaplan-Meier survival curve analysis revealed that increased miR-19b-1 expression was associated with reduced overall survival in clear cell RCC (ccRCC) patients (Logrank p = 0.00047). Moreover, overexpression of this RNA promoted invasion and metastasis of ACHN and 786-O cells (p < 0.05). Conclusions: The significant upregulation of miR-19b-1 correlates strongly with poor prognosis in RCC patients and plays a crucial role in the invasion and metastasis of RCC. This suggests that miR-19b-1 may serve as a viable therapeutic target for RCC
A Study on the Correlation between Recurrent Spontaneous Abortion and the Expression Levels of Serum Interleukin-2 and Heme Oxygenase-1
No full textObjective: The present study aims to explore (1) the changes in the expression of serum interleukin-2 (IL-2) and heme oxygenase-1 (HO-1) in patients with recurrent spontaneous abortion (RSA) and (2) the correlation between IL-2 and HO-1. Method: A total of 45 patients with RSA who (1) were admitted to the Obstetrics and Gynecology Department of the Affiliated Hospital of Inner Mongolia Medical University between June 2018 and December 2020 and (2) met the inclusion criteria were selected as the study subjects and assigned to the observation group. A total of 45 women with normal and early pregnancy were selected from the same hospital as the study subjects and assigned to the normal control group. The expression levels of serum IL-2 and HO-1 in the observation group (before and after successful fetal preservation treatment) and in the control group were detected using the enzyme-linked immunosorbent assay double antibody sandwich method and spectrophotometry. The correlation between the serum IL-2 and HO-1 expression levels in patients with RSA was analyzed. Results: The serum IL-2 expression level before treatment was significantly higher (p < 0.05) and the serum HO-1 expression level was significantly lower (p < 0.05) in the observation group than in the normal control group. In the observation group, the serum IL-2 expression level decreased (p < 0.05) and the HO-1 expression level increased (p < 0.05) after successful fetal preservation treatment. The results of Pearson’s linear correlation analysis showed that the serum IL-2 and HO-1 expression levels were significantly negatively correlated with RSA before and after treatment (r: –0.698 and –0.625, respectively;p < 0.05). The area under curve (AUC) of IL-2 and HO-1 in predicting RSA risk is 0.765 and 0.792 respectively. Conclusions: Serum IL-2 and HO-1 may be involved in maternal and fetal pregnancy immune response and placental nourishment;Furthermore, they are related with the occurrence and development of RSA. Therefore, maternal serum IL-2 and HO-1 expression levels could be served as potential markers for the clinical evaluation of RSA prevention and treatment
Application Value of Serum Cyclophilin A Combined with Double Low Dose Technique and Echocardiography in the Diagnosis of Acute Myocardial Infarction
No full textBackground: Cyclophilin A (CyPA) is one of the important members of cyclophilin family and is well known for its biological function. It mediates macrophages to express matrix metalloproteinase (MMPS) through ERK1/2 and IkB/NF-kB pathways and provides a basis for inflammatory cell infiltration and migration. This study aims to analyze the value of CyPA combined with double low dose technique and echocardiography in the diagnosis of acute myocardial infarction (AMI). Methods: The clinical data of 63 patients with AMI admitted to Zibo Central Hospital from March 2021 to March 2022 were selected as the lesion group (LG) for retrospective analysis. In contrast, 57 healthy people who underwent physical examination in Zibo Central Hospital during the same period were selected as the control group (CG). In total, 120 research subjects were included in this study. All patients in both groups received double low dose of coronary CT angiography (CCTA) and echocardiography examination. The enzyme-linked immunosorbent assay (ELIZA) was adopted to detect serum CyPA level, and the receiver operating characteristic (ROC) curve was used to analyze the application value of serum CyPA. The double low dose of CCTA combined with echocardiography was used for the diagnosis of AMI. Results: The LG had remarkably lower left ventricular ejection fraction (LVEF) levels and higher serum CyPA, left ventricular end diastolic diameter (LVEDD), and Gensini scores than the CG (p < 0.001). Results of logistic regression analysis showed that serum CyPA, LVEF, Gensini scores, and LVEDD were independent risk factors of AMI. The area under the curve of ROC (AUC) value and Youden indexes of the combined diagnosis of the three were higher than those of each single diagnosis. Conclusions: Serum CyPA combined with double low dose technique and echocardiography had higher clinical values in the diagnosis of AMI, which provides the basis for using it for clinical treatment program
Key Potential Long Non-Coding RNAs Related to Plaque Instability in Patients with Carotid Artery Stenosis Analyzed by RNA Sequencing
No full textAim: We aimed to characterize the profiles of long non-coding RNA (lncRNA) and mRNA associated with plaque instability in carotid artery stenosis (CAS). Methods: Three stable and three unstable plaque tissues were collected for RNA sequencing to filtrate differential expressed lncRNAs (DE-lncRNAs) and mRNAs (DE-mRNAs). Identified genes were then used for functional analyses, and six DE-lncRNAs as well as six inflammation-related DE-mRNAs were verified using RT-qPCR (reverse transcription quantitative polymerase chain reaction). Results: Using sequencing, we identified 920 DE-mRNAs (639 upregulated and 281 downregulated mRNAs) and 178 DE-lncRNAs (128 upregulated and 50 downregulated lncRNAs) in unstable plaques. According to functional analysis, these identified genes were obviously enriched in “signal transduction”, “phagocytosis”, “PI3K-Akt (phosphatidylinositol 3 kinase (PI3K)/protein kinaseB) signaling pathway”, “sphingolipid transporter activity”, “TNF (tumor necrosis factor) signaling pathway”, “ICAM-3 (intercellular adhesion molecule-3) receptor activity”, “Jak-STAT (Janus kinase-signal transducer and activator of transcription) signaling pathway”, “interleukin-6 receptor binding”, “Th17 (T helper cell 17) cell differentiation”, “HIF-1 (hypoxia-inducible factor-1) signaling pathway”, “Th1 (helper T lymphocyte 1) and Th2 (helper T lymphocyte 2) cell differentiation”, “NF-κB (nuclear factor kappa-B) signaling pathway”, and “sphingolipid signaling pathway”. Compared to stable plaque tissues, lncRNAs FAM30A, MIAT, and LUCAT1 were significantly upregulated in unstable plaque tissues (p < 0.05), whereas XIST (X inactive-specific transcript) and DLX6-AS1 were markedly downregulated (p < 0.05), based on RT-qPCR results. These findings corroborated expression patterns of lncRNA sequencing data. Compared with stable plaque tissues, expression of CCL19 (chemokine (C-C motif) ligand 19), IL6 (interleukin 6), CCL21 (chemokine (C-C motif) ligand 21), and IL18R1 (interleukin 18 receptor 1) was significantly upregulated, whereas SFRP5 (secreted frizzled related protein 5) was downregulated in unstable plaque tissues. Conclusions: DE-lncRNAs FAM30A, MIAT, LUCAT, XIST, and DLX6-AS1 may be potential targets for plaque instability, and the PI3K-Akt, Jak-STAT, NF-κB, TNF, and HIF-1 signaling pathways may have connection with plaque instability in patients with CAS
Determination of Human T-Cell Leukemia Virus-1 Using a Real-Time Loop-Mediated Isothermal Amplification Assay
No full textBackground: Accurate and rapid detection of human T-cell lymphotropic virus type 1 (HTLV-1) is a critical aspect in monitoring and developing prevention strategies to reduce its transmission rates in blood donors. However, there are two challenges, the expensive reagents and labor-intensive process, faced by the development of HTLV-1 testing. Thus, a real-time loop-mediated isothermal amplification (RT-LAMP)-based method was used for the rapid detection of HTLV-1 in this article. Methods: The PX gene (GenBank: L36905.1) of HTLV-1 was cloned into Escherichia coli DH5a plasmid pUC57 to construct a reference strain for HTLV-1 detection. RT-LAMP primers were designed for the PX gene, the experimental reaction system was optimized, and the specificity and sensitivity of the method were investigated. Results: The optimal reaction system of 25 μL RT-LAMP contained 0.2 μM each of primers outer forward (F3) and backward (B3) primers, 1.6 μM each of forward inner primers (FIP) and backward inner primers (BIP), 0.8 μM each of loop forward (LF) and loop back (LB) primers, 1.2 mM deoxynucleotide triphosphates (dNTPs), 1.0 M betaine, 6 mM MgSO4, and 8 U Bst 3.0 DNA polymerase. Conclusions: The HTLV-1 LAMP method was sensitive, specific, simple-to-operate, and inexpensive, and could be a new method for the rapid detection of HTLV-1