Effect of MiR-16 on Acute Lung Injury in Neonatal Rats Through Regulating NF-κB Pathway

2020 ◽  
Vol 10 (3) ◽  
pp. 360-364
Author(s):  
Yan Xing ◽  
Yuan Liang ◽  
Changsong Shi ◽  
Yudong Miao ◽  
Jianqin Gu ◽  
...  

Acute lung injury represents a widespread, variable type of lung injury characterized by a low oxygen level in the blood, non cardiogenic pulmonary edema, low lung compliance and extensive capillary leakage. In our study, the Wistar rat mode of ALI was established using lipopolysaccharide (LPS). The rats were randomly divided into normal control (NC) group (n = 12) and miR-16 overex-pression group (n = 12), and they were transfected with empty vector and miR-16 overexpression virus, respectively. The lung tissues were extracted in both groups, and then the expression levels of miR-16 and NF-κB were detected via fluorescence quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and the association between their expressions was analyzed via Pearson correlation analysis. Moreover, the morphological changes in lung tissues were detected via hematoxylin-eosin (HE) staining, and the differences in the wet/dry weight (W/D) ratio and the pathomorphological score of lung tissues were compared between the two groups. The expression level of NF-κB was detected via immunohistochemistry (IHC) and Western blotting. Our results showed that, there were different degrees of lung injury in lung tissues in both groups. In miR-16 overexpression group, the W/D ratio was significantly higher than that in NC group (P < 0.05), and the pathomorphological score was also significantly higher than that in NC group (P < 0.05). The results of RT-PCR revealed that the mRNA levels of miR-16 and NF-κB in miR-16 overexpression group were 2.5 and 3.7 times higher than those in NC group. The results of Western blotting and IHC also showed that the activity of NF-κB in lung tissues was evidently enhanced in miR-16 overexpression group compared with that in NC group. According to the Pearson correlation analysis, there was a significant positive correlation between the mRNA levels of miR-16 and NF-κB in lung tissues (r = 0.705, P = 0.012). In conclusion, miR-16 activates the NF-κB pathway to initiate a series of inflammatory responses, thereby contributing to the occurrence of ALI in rats.

2019 ◽  
Author(s):  
Gang Li ◽  
Liangtian Zhang ◽  
Nannan Han ◽  
Ke Zhang ◽  
Hengjie Li

Abstract Background: Acute lung injury (ALI) is one of the major complications of severe sepsis. This study was conducted to investigate the levels of Th22 and Th17 cells in the peripheral blood septic patients with ALI and their clinical significance. Results: A total of 479 septic patients admitted between January 2013 to January 2018 were divided into non-ALI (n = 377) and ALI groups (n = 102) based on the presence or absence of ALI. The levels of Th22 and Th17 cells, interleukin 22 (IL-22), 6 (IL-6) and 17 (IL-17) were determined. Receiver operating characteristic curve (ROC) analysis was performed to assess the early diagnostic value of Th22 and Th17 cells to predict sepsis-induced ALI. The lung injury prediction score (LIPS), IL-6, IL-17, IL-22, and levels of Th17 and Th-22 cells were 9.13, 14.02 ng/L, 13.06 ng/L, 22.90 ng/L, 8.80% and 7.40%, respectively, in the ALI patients and were significantly higher in the ALI group than in non-ALI group (P < 0.05). Pearson correlation analysis showed that LIPS, IL-17, IL-22, Th17 cells and Th22 cells were significant factors affecting sepsis-induced ALI (P < 0.05). The correlation analysis showed that the levels of Th22 cells in the peripheral blood of septic patients with ALI were positively correlated with LIPS, IL-22 and the levels of Th17 cells (P < 0.05), and the levels of Th17 cells were positively correlated with LIPS and IL-17 (P < 0.01). Multivariate logistic regression analysis showed that the LIPS (OR = 1.130), IL-17 (OR = 1.982), IL-22 (OR =2.612) and levels of Th17 (OR = 2.211) and Th22 (OR =3.230) cells were independent risk factor for ALI. The area under the curve of Th22 cells was 0.844 with a cutoff value of 6.81% to predict ALI. The sensitivity and specificity for early diagnosis of sepsis-induced ALI by Th22 cells were 78.72% and 89.13% respectively, which were better but statistically similar as compared with Th17 cells (P > 0.05). Conclusions: The levels of Th22 and Th17 cells in peripheral blood are significantly increased in septic patients with induced ALI, and may be used for early diagnose of sepsis-induced ALI.


2005 ◽  
Vol 98 (5) ◽  
pp. 1777-1783 ◽  
Author(s):  
Sara L. S. Menezes ◽  
Patricia T. Bozza ◽  
Hugo C. Castro Faria Neto ◽  
Andrea P. Laranjeira ◽  
Elnara M. Negri ◽  
...  

To test whether pulmonary and extrapulmonary acute lung injury (ALI) of identical mechanical compromise would express diverse morphological patterns and immunological pathways. For this purpose, a model of pulmonary (p) and extrapulmonary (exp) ALI with similar functional changes was developed and pulmonary morphology (light and electron microscopy), cytokines levels, and neutrophilic infiltration in the bronchoalveolar lavage fluid (BALF), elastic and collagen fiber content in the alveolar septa, and neutrophil apoptosis in the lung parenchyma were analyzed. BALB/c mice were divided into four groups. In control groups, saline was intratracheally (it, 0.05 ml) instilled and intraperitoneally (ip, 0.5 ml) injected, respectively. In the ALIp and ALIexp groups, mice received E. coli lipopolysaccharide (10 μg it and 125 μg ip, respectively). The changes in lung resistive and viscoelastic pressures and in static elastance, alveolar collapse, and cell content in lung tissue were similar in the ALIp and ALIexp groups. The ALIp group presented a threefold increase in KC (murine function homolog to IL-8) and IL-10 levels in the BALF in relation to ALIexp, whereas IL-6 level showed a twofold increase in ALIp. Neutrophils in the BALF were more frequent in ALIp than in ALIexp. ALIp showed more extensive injury of alveolar epithelium, intact capillary endothelium, and apoptotic neutrophils, whereas the ALIexp group presented interstitial edema and intact type I and II cells and endothelial layer. In conclusion, given the same pulmonary mechanical dysfunction independently of the etiology of ALI, insult in pulmonary epithelium yielded more pronounced inflammatory responses, which induce ultrastructural morphological changes.


PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0251578
Author(s):  
Yu Wang ◽  
Xuan Zhang ◽  
Linger Li ◽  
Zhao Zhang ◽  
Chengxi Wei ◽  
...  

Background Ethyl ferulate (EF) is a derivative of ferulic acid (FA), which is a monomeric component purified from the traditional medicinal herb Ferula, but its effects have not been clear yet. The purpose of this study was to evaluate whether EF can reduce inflammation levels in macrophages by regulating the Nrf2-HO-1 and NF-кB pathway. Methods The LPS-induced raw 264.7 macrophage cells model was used to determine the anti-inflammatory and anti-oxidative stress effects of EF. The levels of IL-1β, IL-6, TNF-α and PGE2 were analyzed by ELISA. The mRNA and protein of COX-2, iNOS, TNF-α, IL-6, HO-1 and Nrf2 were identified by RT-PCR analysis and western blotting. Intracellular ROS levels were assessed with DCFH oxidation staining. The expressions of NF-кB p-p65 and Nrf2 were analyzed by immunofluorescence assay. The inhibitory effect of Nrf2 inhibitor ML385 (2μM) on mediatation of antioxidant activity by raw 264.7 macrophage cells was evaluated. The effect of EF was confirmed in acute lung injury mice model. Results In our research, EF reduced the expression of iNOS, COX2 and the production of PGE2. EF could inhibit the production of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) in lipopolysaccharide (LPS) stimulated macrophages and decreased expression of IL-6 and TNF-α in LPS stimulated macrophages. Furthermore, EF inhibited NF-кB p65 from transporting to the nucleus, decreased the expression of p-IкBα, significantly decreased the level of intracellular reactive oxygen species (ROS) and activated Nrf2/HO-1 pathways. EF could attenuate the degree of leukocyte infiltration, reduced MPO activity, mRNA levels and secretion of TNF-α and IL-6 in vivo. EF exhibited potent protective effects against LPS-induced acute lung injury in mice. Conclusions Collectively, our data showed that EF relieved LPS-induced inflammatory responses by inhibiting NF-κB pathway and activating Nrf2/HO-1 pathway, known to be involved in the regulation of inflammatory responses by Nrf2.


2021 ◽  
Author(s):  
Yan Li ◽  
Xiaoying Wang ◽  
Yue Han ◽  
Xun Li

Abstract Background: Long non-coding RNAs (lncRNAs) play an important role in angiogenesis, immune response, inflammatory response and tumor development and metastasis. m6 A (N6 - methyladenosine) is one of the most common RNA modifications in eukaryotes. The aim of our research was to investigate the potential prognostic value of m6A-related lncRNAs in ovarian cancer (OC).Methods: The data we need for our research was downloaded from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. Pearson correlation analysis between 21 m6A regulators and lncRNAs was performed to identify m6A-related lncRNAs. Univariate Cox regression analysis was implemented to screen for lncRNAs with prognostic value. A least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox regression analyses was used to further reduct the lncRNAs with prognostic value and construct a m6A-related lncRNAs signature for predicting the prognosis of OC patients. Results: 275 m6A-related lncRNAs were obtained using pearson correlation analysis. 29 m6A-related lncRNAs with prognostic value was selected through univariate Cox regression analysis. Then, a seven m6A-related lncRNAs signature was identified by LASSO Cox regression. Each patient obtained a riskscore through multivariate Cox regression analyses and the patients were classified into high-and low-risk group using the median riskscore as a cutoff. Kaplan-Meier curve revealed that the patients in high-risk group have poor outcome. The receiver operating characteristic curve revealed that the predictive potential of the m6A-related lncRNAs signature for OC was powerful. The predictive potential of the m6A-related lncRNAs signature was successfully validated in the GSE9891, GSE26193 datasets and our clinical specimens. Multivariate analyses suggested that the m6A-related lncRNAs signature was an independent prognostic factor for OC patients. Moreover, a nomogram based on the expression level of the seven m6A-related lncRNAs was established to predict survival rate of patients with OC. Finally, a competing endogenous RNA (ceRNA) network associated with the seven m6A-related lncRNAs was constructed to understand the possible mechanisms of the m6A-related lncRNAs involed in the progression of OC.Conclusions: In conclusion, our research revealed that the m6A-related lncRNAs may affect the prognosis of OC patients and identified a seven m6A-related lncRNAs signature to predict the prognosis of OC patients.


2016 ◽  
Vol 1 (1) ◽  
pp. 27-42
Author(s):  
Hazlin Kadir @ Shahar ◽  
Razaleigh Muhamat @ Kawangit ◽  
Rosmawati Mohamad Rasit ◽  
Badlihisham Mohd Nasir

This article examines the relationship between learning and behavioural evaluation among religious officers in Malaysia after attending the Manual on HIV/AIDS in Islam Training Programmes organized by the Islamic Development Department of Malaysia (JAKIM). The training programmes were implemented to deliver the most accurate and the latest information on HIV / AIDS as well as to train religious officers in Malaysia to address the issues among Muslims. The training programmes apply the theoretical and practical activities where participants had the opportunity to carry out outreach activities with People Living with HIV / AIDS (ODHA). Quantitative methods through questionnaires were used to obtain data. A total of 350 religious officers who had attended the training programmes were selected as respondents by simple random sampling technique. Pearson correlation analysis was conducted to determine the relationship between the learning and behavioural evaluation. The results of the Pearson correlation analysis found that there was a significant relationship between learning evaluation in terms of the information obtained from programmes’ contents and behaviour evaluation with r = 0.489 and sig = 0.000 (p <0.05) at the medium positive range.. While the relationship between learning evaluation in terms of the information obtained from outreach activities with behavioural evaluation showed a strong positive correlation with the strength values obtained were r = 0.539 and sig = 0.000 (p <0.05). This analysis shows that the information acquired through the training program Manual Islam and HIV / AIDS has been successful in changing the behaviour of religious officers’ awareness in terms of the role of dakwah to ODHA. ABSTRAK Artikel ini bertujuan melihat hubungan antara penilaian pembelajaran dengan penilaian tingkah laku dalam kalangan Pegawai Agama di Malaysia setelah mengikuti Program Latihan Manual Islam dan HIV/AIDS anjuran Jabatan Kemajuan Islam Malaysia (JAKIM). Program latihan ini dilaksanakan untuk menyampaikan maklumat yang tepat serta informasi terkini isu HIV/AIDS di samping melatih Pegawai-pegawai Agama di Malaysia untuk menangani isu tersebut dalam kalangan umat Islam. Program latihan ini berbentuk teori dan praktikal di mana peserta program berpeluang melaksanakan dakwah secara temu seru (outreach) dengan Orang Yang Hidup dengan HIV/AIDS (ODHA) secara langsung. Kaedah kuantitatif melalui soal selidik telah digunakan untuk memperoleh data. Seramai 350 orang Pegawai Agama yang telah mengikuti program latihan ini dipilih sebagai responden melalui teknik pensampelan rawak mudah. Analisis korelasi Pearson dijalankan bagi mengenal pasti hubungan di antara penilaian pembelajaran dengan penilaian tingkah laku peserta yang mengikuti Program Latihan Manual Islam dan HIV/AIDS. Hasil analisis ujian korelasi Pearson tersebut mendapati bahawa terdapat hubungan yang signifikan di antara penilaian pembelajaran dari segi maklumat yang diperoleh daripada kandungan program dengan penilaian tingkah laku dengan nilai r = 0.489 dan sig = 0.000 (p<0.05). Kekuatan hubungan ialah positif sederhana. Manakala hubungan antara penilaian pembelajaran dari segi maklumat yang diperoleh daripada program temu seru dengan penilaian tingkah laku pula menunjukkan kekuatan hubungan positif kuat dengan nilai yang diperoleh ialah r = 0.539 dan sig = 0.000 (p<0.05). Analisis ini menunjukkan bahawa pembelajaran yang diperoleh melalui program latihan Manual Islam dan HIV/AIDS ini telah berjaya mengubah tingkah laku Pegawai Agama dari segi kesedaran peranan berdakwah kepada ODHA.


2020 ◽  
Author(s):  
XiaoMei Huang ◽  
ZeXun Mo ◽  
YuJun Li ◽  
Hua He ◽  
KangWei Wang ◽  
...  

Abstract Background Nuclear factor kappa-B (NF-κB) activation increased the expression of cytokines and further lead to lung injury was considered the main mechanism of acute lung injury (ALI). Here, we focus on exploring the potential regulatory mechanism between long noncoding RNA (LncRNA) HOX transcript antisense RNA (HOTAIR) and NF-κB on LPS-induced ALI. Methods A549 cells were then divided into 4 groups: HOTAIR group, NC group, si-HOTAIR group and si-NC group. These 4 groups were then treated with 1μg/mL lipopolysaccharides (LPS) or without LPS at 37°C for 24 h. The expression level of cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6) and LncRNA HOTAIR were evaluated by quantitative Real Time Polymerase Chain Reaction (qRT-PCR) and Enzyme-linked immunosorbent assay (ELISA). Western Blot analysis was adopted for evaluating the level of p-IκBα/IκBα and p-p65/p65. Nuclear translocation of p65 was observed by immunofluorescence staining. Results qRT-PCR and ELISA assay showed that the expression of cytokines (IL-1β, IL-6 and TNF-α) and inflammatory gene HOTAIR was remarkably increased with LPS treatment (p < 0.01). Over-expression of HOTAIR significantly increased the expression of cytokines (including IL-1β, IL-6 and TNF-α) and NF-κB pathway associated proteins (including p-IκBα/IκBα and p-p65/p65), while knockdown of HOTAIR had the opposite effect (p < 0.01). The immunofluorescence assay showed that the level of p65 in the nucleus was significantly higher in the HOTAIR group and significantly lowers in the si-HOTAIR group (p < 0.01). Conclusion HOTAIR may play a pro-inflammatory response through NF-κB pathway in LPS-induced ALI, which may provide a perspective for further understanding the pathogenic mechanism of ALI.


2020 ◽  
Vol 5 (1) ◽  
pp. 45-53
Author(s):  
Safa’a Ahmad Al Masri ◽  
Siti Musliha Mat Rasid

In the current study, a total of 86 soccer’s players with mean age of 14 years drawn from Terengganu soccer academy were tested in performing 10 parameters aiming at determining the performance of those players based on assessing the contribution of each activity and its corresponding significant level. The 10 performance related parameters involved anthropometry (BMI), fitness test (agility, coordination, muscular endurance (push and sit up), power, YoYo level), and football skill test (dribbling with ball, dribbling without ball and juggling).  All the parameters testing is carried out based on international standard and performed by well-trained staff.  The Pearson correlation analysis was used to achieve the objective in this study. Result shows a positive correlation between the two types of muscular parameters; the power is influenced by BMI and coordination; the specific football tests are highly impacted by the power and agility. The coefficient of determination  and the significance level -values show that the parameters that can be significantly considered are the anthropometric BMI (0.020), agility (0.025), muscular endurance (0.039 and 0.043), power (0.039), special football test without the ball (0.041), and juggling (0.046). The coordination, YoYo, football special test with the ball were not found to be significantly accounted for preparing the young players to achieve the required performance. Based on the results of the coefficient of determination and the significance -values of the parameters, a model was proposed to determine the highest and lowest parameters that play important roles in the selection of young players.


2018 ◽  
Vol 17 (7) ◽  
pp. 975-983 ◽  
Author(s):  
Luiz Philippe da Silva Sergio ◽  
Andrezza Maria Côrtes Thomé ◽  
Larissa Alexsandra da Silva Neto Trajano ◽  
Andre Luiz Mencalha ◽  
Adenilson de Souza da Fonseca ◽  
...  

Acute lung injury (ALI) is defined as hyperinflammation that could occur from sepsis and lead to pulmonary permeability and edema, making them life-threatening diseases.


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