Clinical significance of serum miR-101-3p expression in patients with neonatal sepsis

2021 ◽  
Author(s):  
Juan Zhang ◽  
Xinwei Xu ◽  
Min Wang
Keyword(s):  
Neonatal Sepsis ◽  
Target Gene ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Quantitative Real Time Pcr ◽  
Tnf Α ◽  
Direct Target Gene ◽  
Direct Target ◽  
Operating Characteristic Curve

Aim: This study aimed to evaluate the levels and functions of miR-101-3p in neonatal sepsis (NS). Materials & methods: Quantitative real-time PCR was conducted to investigate the expression of miR-101-3p and the receiver operating characteristic curve was applied to manifest its diagnostic effects. Results: MiR-101-3p was increased in the NS patients and the dysregulation of miR-101-3p was associated with levels of procalcitonin, CRP, IL-8 and TNF-α. The combination of miR-101-3p and procalcitonin could function as a promising indicator in distinguishing NS patients. The silenced miR-101-3p reversed the increased levels of TNF-α and IL-8 caused by lipopolysaccharide in vitro. DUSP1 was identified as a direct target gene of miR-101-3p in NS. Conclusion: The abundance of miR-101-3p facilitated the inflammation in NS by targeting DUSP1.

scholarly journals SEMA6D, Negatively Regulated by miR-7, Contributing to Chondrocyte Catabolic and Anabolic Activities via p38 Signaling Pathway

2020 ◽  
Author(s):  
Xindie Zhou ◽  
Yi Zhang ◽  
Junjie Zhang ◽  
Zhicheng Yang ◽  
Haoyu Yang ◽  
...  
Keyword(s):  
Target Gene ◽  
Regulatory Mechanism ◽  
Regulatory Factor ◽  
Regulatory Relation ◽  
Direct Target Gene ◽  
Direct Target ◽  
Novel Therapeutic ◽  
P38 Pathway

Abstract Background: MiR-7 has been recognized as a promoting factor of osteoarthritis (OA), but the specific down-stream pathway of miR-7 still remains unknown. Further investigation of the molecular regulatory mechanism of miR-7 might help develop a novel therapeutic method for OA.Results: Here we revealed that Semaphorin 6D (SEMA6D) was a direct target gene of miR-7, of which presented a negatively regulatory relation in vitro and in vivo. Lucubration of SEMA6D suggested that SEMA6D is validated to promote the anabolic metabolism and reduce the catabolism of chondrocytes via inhibiting the activation of p38 pathway.Conclusions: Present research illustrated that SEMA6D is a negatively regulatory factor of miR-7 and a pivotal mediator of the catabolism and anabolism of chondrocytes. SEMA6D exerts its function via inhibiting the activation of p38 pathway.

scholarly journals WSB1 Regulates c-Myc Expression Through β-catenin Signaling and Forms a Feedforward Circuit Promoting the Development of Cancer

2020 ◽  
Author(s):  
Xiaomeng Gao ◽  
Yanling Gong ◽  
Jieqiong You ◽  
Meng Yuan ◽  
Haiying Zhu ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Target Gene ◽  
Regulatory Mechanism ◽  
Intervention Strategy ◽  
E3 Ubiquitin Ligase ◽  
Promoting Effect ◽  
Direct Target Gene ◽  
Direct Target

AbstractThe dysregulation of transcription factors is widely associated with tumorigenesis. As the most well-defined transcription factor in multiple types of cancer, c-Myc can directly transform cells by transactivating various downstream genes. Given that there is no effective way to directly inhibit c-Myc, c-Myc targeting strategies based on its regulatory mechanism hold great potential for cancer therapy. In this study, we found that WSB1, a direct target gene of c-Myc, can positively regulate c-Myc expression, which forms a feedforward circuit promoting cancer development. Luciferase-based promoter activity assays and RNA sequencing results confirmed that WSB1 promoted c-Myc expression through the β-catenin pathway. Mechanistically, WSB1 affected β-catenin destruction complex-PPP2CA assembly and E3 ubiquitin ligase adaptor β-TRCP recruitment, which inhibited the ubiquitination of β-catenin and subsequently transactivated c-Myc. Of interest, the promoting effect of WSB1 on c-Myc was independent of its E3 ligase activity. Moreover, co-expression of WSB1 and c-Myc strongly enhanced the initiation and progression of tumours both in vitro and in vivo. Thus, our findings revealed a novel mechanism involved in tumorigenesis in which the WSB1/c-Myc feedforward circuit played an essential role, highlighting a potential c-Myc intervention strategy in cancer treatment.

scholarly journals MiR-429 Determines Poor Outcome and Inhibits Pancreatic Ductal Adenocarcinoma Growth by Targeting TBK1

2015 ◽  
Vol 35 (5) ◽  
pp. 1846-1856 ◽  
Author(s):  
Bin Song ◽  
Kailian Zheng ◽  
Hongyun Ma ◽  
Anan Liu ◽  
Wei Jing ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Cell Lines ◽  
Target Gene ◽  
Target Genes ◽  
Ductal Adenocarcinoma ◽  
Direct Target Gene ◽  
Direct Target ◽  
Sw1990 Cell ◽  
High Level

Background: Pancreatic ductal adenocarcinoma (PDAC) ranks fourth on the list of cancer-related causes of death and its prognosis has not improved significantly over the past decades. Deregulation or dysfunction of miRNAs contribute to cancer development. Previous data indicates that miR-429 is involved in the pathogenesis of PDAC. However, the role of miR-429 in PDAC remained unknown. Methods: MiR-429 levels in sample tissues of 78 patients and in PANC1 and SW1990 cell lines were quantified by real-time PCR. MiR-429 expression was modulated using specific pre- and anti-miRNAs and cell growth was assayed by MTT analysis. Bioinformatics prediction of the miR-429 putative target genes was performed and luciferase assays confirmed TBK1 as a direct target gene. TBK1 levels in PDAC tissues were analyzed by immunohistochemistry. Results: MiR-429 was remarkably decreased in PDAC tissues and cell lines. Lower miR-429 expression in PDAC tissues significantly correlated with shorter survival of PDAC patients. Overexpression of miR-429 inhibited PDAC cell lines growth in vitro and vice versa. TBK1 was found to be the direct target gene of miR-429. Higher TBK1 protein level in PDAC tissues correlated with shorter survival of PDAC patients. Overexpression of TBK1 partly restored cell proliferation. Conclusions: Low level of miR-429 and high level of TBK1 in PDAC promoted PDAC cells growth which might be related to the low survival rate of PDAC patients. MiR-429 play its role in PDAC by targeting TBK1.

Regulation of Ci-tropomyosin-like, a Brachyury target gene in the ascidian, Ciona intestinalis

Development ◽  
1999 ◽  
Vol 126 (24) ◽  
pp. 5599-5609 ◽  
Author(s):  
A. Di Gregorio ◽  
M. Levine
Keyword(s):  
Target Gene ◽  
Target Genes ◽  
Ciona Intestinalis ◽  
Subtractive Hybridization ◽  
Flanking Sequence ◽  
Binding Assays ◽  
Specific Staining ◽  
Direct Target Gene ◽  
Direct Target

Brachyury is a sequence-specific transcriptional activator that is essential for notochord differentiation in a variety of chordates. In vertebrates, Brachyury is expressed throughout the presumptive mesoderm, but becomes restricted to the notochord at later stages of development. In ascidians, such as Ciona intestinalis, Brachyury is expressed exclusively in the notochord and does not exhibit an early pan-mesodermal pattern. Subtractive hybridization screens were recently used to identify potential Ciona Brachyury (Ci-Bra) target genes (Takahashi, H., Hotta, K., Erives, A., Di Gregorio, A., Zeller, R. W., Levine, M. and Satoh, N. (1999). Genes Dev. 13, 1519–1523). Of the genes that were identified in this screen, one corresponds to a new member of the tropomyosin superfamily, Ciona tropomyosin (Ci-trop). Here we show that Ci-trop is specifically expressed in the developing notochord beginning at gastrulation, and expression persists in the notochord during tailbud and tadpole stages. A 3 kb region of the Ci-trop 5′-flanking sequence was characterized via electroporation of lacZ fusion genes into fertilized Ciona eggs. A minimal, 114 bp enhancer was identified that is sufficient to direct the expression of a heterologous promoter in the notochord. DNA binding assays indicate that this enhancer contains two sets of low-affinity Brachyury half-sites, which are bound in vitro by a GST/Ci-Bra fusion protein. Deletion of the distal sites inactivates the notochord-specific staining pattern mediated by an otherwise normal Ci-trop/lacZ transgene. These results suggest that Ci-trop is a direct target gene of Ci-Bra and that Brachyury plays an immediate role in the cellular morphogenesis of the notochord.

scholarly journals circCRAMP1L is a novel biomarker of preeclampsia risk and may play a role in preeclampsia pathogenesis via regulation of the MSP/RON axis in trophoblasts

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Yonggang Zhang ◽  
Hongling Yang ◽  
Yipeng Zhang ◽  
Junzhu Shi ◽  
Ronggui Chen
Keyword(s):  
Cell Proliferation ◽  
Receiver Operating Characteristic Curve ◽  
Pregnant Women ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Trophoblast Cell ◽  
Luciferase Reporter ◽  
Rna Immunoprecipitation ◽  
Operating Characteristic Curve

Abstract Background Preeclampsia is a severe disease in pregnant women, which is primarily managed by early screening and prevention. Circular RNAs (circRNAs) have increasingly been shown to be important biological regulators involved in numerous diseases. Further, increasing evidence has demonstrated that circRNAs can be used as diagnostic biomarkers. This study was conducted to evaluate the potential of circCRAMP1L, previously identified to be downregulated in preeclampsia, as a novel biomarker for predicting the development of preeclampsia. Methods We measured the expression of circCRAMP1L, which is reportedly relevant to trophoblast physiology, in plasma samples from 64 patients with preeclampsia and 64 age-, gestational age-, and body mass index-matched healthy pregnant women by qRT-PCR. MTT proliferation and transwell invasion assays revealed the biological role of circCRAMP1L in preeclampsia pathogenesis. RNA immunoprecipitation and dual-luciferase reporter assays clarified the mechanism underlying the biological function of circCRAMP1L in TEV-1 cells. Results circCRAMP1L circulating levels were significantly lower in patients with preeclampsia (2.66 ± 0.82, △Ct value) than in healthy pregnant women (3.95 ± 0.67, △Ct value, p <  0.001). The area under the receiver operating characteristic curve for circCRAMP1L was 0.813. Univariate and multivariate analyses identified circCRAMP1L as an independent predictor of preeclampsia. Furthermore, when circCRAMP1L was utilised in combination with its target protein macrophage stimulating protein (MSP), the predictive performance increased, with an area under the receiver operating characteristic curve of 0.928 (95% CI 0.882–0.974), 80.0% sensitivity, and 80.0% specificity. The in vitro results indicated that circCRAMP1L regulates cell proliferation, and invasion via MSP and RON proteins. We investigated the molecular mechanisms of these effects. In vitro, relative to the control group, circCRAMP1L overexpression significantly enhanced cell proliferation; furthermore, trophoblast cell invasion increased proportionally with circCRAMP1L expression. RNA immunoprecipitation and luciferase reporter gene illustrated that circCRAMP1L participated in regulation of trophoblast cell by regulating MSP. Conclusion Reduced plasma levels of circCRAMP1L may be associated with an increased risk of preeclampsia, and circCRAMP1L may be a novel biomarker of preeclampsia risk.

scholarly journals Proanthocyanidins Induce miR-133b Expression to Promote Ischemic Skeletal Muscle Regeneration by Targeting MKP1

2020 ◽  
Author(s):  
Shi Chen ◽  
Chao Du ◽  
Lilong Pan ◽  
Qian Yang ◽  
Peihe Yu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Target Gene ◽  
Myogenic Differentiation ◽  
Limb Ischemia ◽  
Skeletal Muscle Regeneration ◽  
Aberrant Expression ◽  
Direct Target Gene ◽  
Direct Target

Abstract Background: Limb ischemic necrosis is mainly attributed to peripheral arterial disease (PAD). Reducing oxidative stress and promoting damaged skeletal muscle regeneration may be benefit for ischemic limb treatment. Proanthocyanidins (PC) is a powerful antioxidant and free radical scavenger, but little is known about its role and related molecular mechanism in limb ischemic injury. The current study was undertaken to explore its role in the damaged skeletal muscle regeneration both in vitro and vivo, and whether MicroRNAs (miRNAs) involved in this process. Methods: The potential effects of PC on the damaged muscle regeneration were explored in human skeletal muscle satellite cells (HSKMSCs) under hypoxic-ischemic condition and in mice limb ischemia model, then, aberrant expression of miRNAs in ischemic skeletal muscles were determined by microarray analysis, and regulatory mechanism of the specific miRNA on HSKMSCs myogenic differentiation was further investigated by gain and loss of functional experiments. Additionally, the direct target gene was examined by luciferase reporter assay.Results: In mice limb ischemia model, our results revealed that PC reduced oxidative stress level, significantly promoted ischemic limb damaged muscle regeneration and motor function recovery, then, aberrant expression of miRNAs in ischemic skeletal muscles were determined by microarray analysis, combine with the results of the RT-qPCR, the miR-133b-3p was proved to be the specific miRNA. In vitro, our results revealed that PC induced the overexpression of miR-133b to activate the p38-MAPK signal pathway and increased the myogenic differentiation-related molecules expression, which eventually promoted myotubes formation. Furthermore, MKP1 was confirmed a direct target gene of miR-133b.Conclusion: Our results suggest that PC display skeletal muscle protective properties that are mediated by miR-133b /MKP1/ p38-MAPK signal axis, offering a novel therapeutic opportunity for limb ischemic injury.

Serum miR-21 and miR-26a Levels Negatively Correlate with Severity of Cirrhosis in Patients with Chronic Hepatitis B

MicroRNA ◽  
2018 ◽  
Vol 8 (1) ◽  
pp. 86-92 ◽  
Author(s):  
Shili Jiang ◽  
Wei Jiang ◽  
Ying Xu ◽  
Xiaoning Wang ◽  
Yongping Mu ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Curve Analysis ◽  
Pugh Class ◽  
Operating Characteristic Curve ◽  
Class C ◽  
Circulating Levels

Background and Objective: Accurately evaluating the severity of liver cirrhosis is essential for clinical decision making and disease management. This study aimed to evaluate the value of circulating levels of microRNA (miR)-26a and miR-21 as novel noninvasive biomarkers in detecting severity of cirrhosis in patients with chronic hepatitis B. </P><P> Methods: Thirty patients with clinically diagnosed chronic hepatitis B-related cirrhosis and 30 healthy individuals were selected. The serum levels of miR-26a and miR-21 were quantified by qRT-PCR. Receiver operating characteristic curve analysis was performed to evaluate the sensitivity and specificity of the miRNAs for detecting the severity of cirrhosis. Results: Serum miR-26a and miR-21 levels were found to be significantly downregulated in patients with severe cirrhosis scored at Child-Pugh class C in comparison to healthy controls (miR-26a p<0.01, and miR-21 p<0.001, respectively). The circulating miR-26a and miR-21 levels in patients were positively correlated with serum albumin concentration but negatively correlated with serum total bilirubin concentration and prothrombin time. Receiver operating characteristic curve analysis revealed that both serum miR-26a and miR-21 levels were associated with a high diagnostic accuracy for patients with cirrhosis scored at Child-Pugh class C (miR-26a Cut-off fold change at ≤0.4, Sensitivity: 84.62%, Specificity: 89.36%, P<0.0001; miR-21 Cut-off fold change at ≤0.6, Sensitivity: 84.62%, Specificity: 78.72%, P<0.0001). Our results indicate that the circulating levels of miR-26a and miR-21 are closely related to the extent of liver decompensation, and the decreased levels are capable of discriminating patients with cirrhosis at Child-Pugh class C from the whole cirrhosis cases.

A validated novel preoperative index to predict the extent of intraperitoneal contamination in patients with acute abdominal pathology: A cohort study

2019 ◽  
Vol 30 (7-8) ◽  
pp. 221-228
Author(s):  
Shahab Hajibandeh ◽  
Shahin Hajibandeh ◽  
Nicholas Hobbs ◽  
Jigar Shah ◽  
Matthew Harris ◽  
...  
Keyword(s):  
Receiver Operating Characteristic Curve ◽  
Receiver Operating Characteristic ◽  
Operating Characteristic ◽  
Validation Cohort ◽  
Characteristic Curve ◽  
Curve Analysis ◽  
Emergency Laparotomy ◽  
Contamination Index ◽  
Operating Characteristic Curve ◽  
Receiver Operating

Aims To investigate whether an intraperitoneal contamination index (ICI) derived from combined preoperative levels of C-reactive protein, lactate, neutrophils, lymphocytes and albumin could predict the extent of intraperitoneal contamination in patients with acute abdominal pathology. Methods Patients aged over 18 who underwent emergency laparotomy for acute abdominal pathology between January 2014 and October 2018 were randomly divided into primary and validation cohorts. The proposed intraperitoneal contamination index was calculated for each patient in each cohort. Receiver operating characteristic curve analysis was performed to determine discrimination of the index and cut-off values of preoperative intraperitoneal contamination index that could predict the extent of intraperitoneal contamination. Results Overall, 468 patients were included in this study; 234 in the primary cohort and 234 in the validation cohort. The analyses identified intraperitoneal contamination index of 24.77 and 24.32 as cut-off values for purulent contamination in the primary cohort (area under the curve (AUC): 0.73, P < 0.0001; sensitivity: 84%, specificity: 60%) and validation cohort (AUC: 0.83, P < 0.0001; sensitivity: 91%, specificity: 69%), respectively. Receiver operating characteristic curve analysis also identified intraperitoneal contamination index of 33.70 and 33.41 as cut-off values for feculent contamination in the primary cohort (AUC: 0.78, P < 0.0001; sensitivity: 87%, specificity: 64%) and validation cohort (AUC: 0.79, P < 0.0001; sensitivity: 86%, specificity: 73%), respectively. Conclusions As a predictive measure which is derived purely from biomarkers, intraperitoneal contamination index may be accurate enough to predict the extent of intraperitoneal contamination in patients with acute abdominal pathology and to facilitate decision-making together with clinical and radiological findings.

scholarly journals Evaluation of factors that predict the success rate of trial of labor after the cesarean section

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yang Mi ◽  
Pengfei Qu ◽  
Na Guo ◽  
Ruimiao Bai ◽  
Jiayi Gao ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Cesarean Section ◽  
Receiver Operating Characteristic Curve ◽  
Success Rate ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Predictive Ability ◽  
Training Set ◽  
History Of ◽  
Operating Characteristic Curve

Abstract Background For most women who have had a previous cesarean section, vaginal birth after cesarean section (VBAC) is a reasonable and safe choice, but which will increase the risk of adverse outcomes such as uterine rupture. In order to reduce the risk, we evaluated the factors that may affect VBAC and and established a model for predicting the success rate of trial of the labor after cesarean section (TOLAC). Methods All patients who gave birth at Northwest Women’s and Children’s Hospital from January 2016 to December 2018, had a history of cesarean section and voluntarily chose the TOLAC were recruited. Among them, 80% of the population was randomly assigned to the training set, while the remaining 20% were assigned to the external validation set. In the training set, univariate and multivariate logistic regression models were used to identify indicators related to successful TOLAC. A nomogram was constructed based on the results of multiple logistic regression analysis, and the selected variables included in the nomogram were used to predict the probability of successfully obtaining TOLAC. The area under the receiver operating characteristic curve was used to judge the predictive ability of the model. Results A total of 778 pregnant women were included in this study. Among them, 595 (76.48%) successfully underwent TOLAC, whereas 183 (23.52%) failed and switched to cesarean section. In multi-factor logistic regression, parity = 1, pre-pregnancy BMI < 24 kg/m2, cervical score ≥ 5, a history of previous vaginal delivery and neonatal birthweight < 3300 g were associated with the success of TOLAC. The area under the receiver operating characteristic curve in the prediction and validation models was 0.815 (95% CI: 0.762–0.854) and 0.730 (95% CI: 0.652–0.808), respectively, indicating that the nomogram prediction model had medium discriminative power. Conclusion The TOLAC was useful to reducing the cesarean section rate. Being primiparous, not overweight or obese, having a cervical score ≥ 5, a history of previous vaginal delivery or neonatal birthweight < 3300 g were protective indicators. In this study, the validated model had an approving predictive ability.

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