MiRNA-1976 Regulates the Apoptosis of Dopaminergic Neurons by Targeting the PINK1 Gene.

INTRODUCTION: Parkinson's disease (PD), which is a neurodegenerative disease, requires urgently needed biomarkers to explore its mechanism. We screened for differences in the expression of microRNAs (miRNAs) and identified miR-1976 as a possible biomarker. METHODS: Twenty-three patients and 30 controls were included in this study. Dopaminergic neurons from C57/BL mice were cultured. The miRNA expression profiles were analyzed using an miRNA microarray. MiR-1976 was identified as an miRNA that was differentially expressed between PD patients and age-matched controls. Lentiviral vectors were constructed, then apoptosis in dopaminergic neurons was analyzed using MTS (multicellular tumor spheroids) and flow cytometry. Transfection of miR-1976 mimics into MES23.5 cells was performed, and target genes and biological effects were analyzed. RESULTS: Overexpression of miR-1976 increased apoptosis and mitochondrial damage in dopaminergic neurons. PINK1 (PINK1-induced kinase 1) was the most common target protein of miR-1976, and silencing of PINK1 caused mitochondrial damage and increased apoptosis of MES23.5 cells. CONCLUSIONS: MiR-1976 is a newly discovered miRNA that exhibits a high degree of differential expression with respect to the apoptosis of dopaminergic neurons. Given these results, increased expression of miR-1976 may increase the risk of PD by targeting PINK1 and may therefore be a useful biomarker for PD.

Pediatric Reference Change Value Optimized for Acute Kidney Injury: Multicenter Retrospective Study in China.

OBJECTIVES: The standard definition of pediatric acute kidney injury (AKI) is evolving, especially for critically ill in the PICU. We sought to validate the application of the Pediatric Reference Change Value Optimized for Acute Kidney Injury in Children (pROCK) criteria in critically ill children. DESIGN: Multicenter retrospective study. SETTING: Six PICUs in mainland China. PATIENTS: One thousand six hundred seventy-eight hospitalized children admitted to the PICU with at least two creatinine values within 7 days. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: AKI was diagnosed and staged according to the Pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease (pRIFLE), the Kidney Disease Improving Global Outcomes (KDIGO), and the pROCK criteria. Multiple clinical parameters were assessed and analyzed along with 90-day follow-up outcomes. According to the definitions of pRIFLE, KDIGO, and pROCK, the prevalence of AKI in our cohort of 1,678 cases was 52.8% (886), 39.0% (655), and 19.0% (318), respectively. The presence of AKI, as defined by pROCK, was associated with increased number of injured organs, occurrence of sepsis, use of mechanical ventilation, use of continuous renal replace therapy ( p < 0.05), higher Pediatric Risk of Mortality III score, and higher Pediatric Logistic Organ Dysfunction-2 score ( p < 0.001). The survival curve of 90-day outcomes showed that pROCK was associated with shorter survival time (LogRank p < 0.001), and pROCK definition was associated with better separation of the different stages of AKI from non-AKI ( p < 0.001). CONCLUSIONS: In this retrospective analysis of AKI criteria in PICU admissions in China, pROCK is better correlated with severity and outcome of AKI. Hence, the pROCK criteria for AKI may have better utility in critically ill children.

Effects of prone positioning during extracorporeal membrane oxygenation for refractory respiratory failure: a systematic review.

As more and more studies have shown that venovenous extracorporeal membrane oxygenation (VV-ECMO) improves oxygenation and prognosis of critical patients, VV-ECMO has been frequently used in critical patients for severe acute respiratory distress syndrome (ARDS). Prone positioning (PP) is a postural therapy for ARDS, which permits for better ventilation/perfusion ratio (V/Q) matching, improvement of hypoxemia. Some articles revealed that performing PP during ECMO for refractory respiratory failure is feasible; however, the results obtained were controversial. Therefore, we performed a systematic review to further assess the effects of PP during ECMO for refractory respiratory failure. Six studies with 465 subjects were enrolled. Four articles examined changes of PaO2/FiO2 ratio after PP during VV-ECMO; PaO2/FiO2 ratio improved from 18.5 to 62 mmHg. Our analysis inferred that the PP-ECMO group did not have a significant advantage in survival at discharge (odds risk 1.42, 95% confidence interval 0.92-2.18; p = 0.11) compared with the ECMO group. We found that the PP-ECMO group had a significantly longer duration than the ECMO group (MD 5.37, 95% CI 4.19-6.54, I2 = 67%, P < .00001). ICU length of stay in the PP-ECMO group was significantly longer than the ECMO group (MD 7.29, 95% CI 4.06-10.52, I2 = 64%, P < .00001). No unplanned extubation of ECMO was recorded. In conclusion, our review found that performing PP during ECMO for refractory respiratory failure is safe and PP can improve the PaO2/FiO2 ratio, which is in line with the length of PP performed.

Changes of coagulation function and risk of stroke in patients with COVID-19.

BACKGROUND AND PURPOSE: COVID-19 is spreading throughout the whole world as a public health issue. There is a link between the new coronavirus and changes in biochemical indicators, such as coagulation functions. Hypercoagulable state of blood caused by infections may lead to cerebrovascular diseases. More attention should be paid to patients with COVID-19, especially critically ill individuals with history of cerebrovascular disease who may have high risk of stroke. METHODS: 193 patients with COVID-19 were enrolled in the study. These patients were categorized into nonsevere (143 patients) and severe (50 patients) groups. This study evaluated laboratory tests, including routine blood tests, C-reactive protein, erythrocyte sedimentation rate, electrolytes, and coagulation functions. Furthermore, neurological function and stroke risks were evaluated in this study. RESULTS: Compared to the nonsevere group, there were increases in white blood cells, neutrophil count, interleukin-6, erythrocyte sedimentation rate, and C-reactive protein in the severe group (p < .05). For coagulation functions, parameters like prothrombin time, international normalized ratio, activated partial thromboplastin time, thrombin time, D-dimer, and fibrin degradation products were increased significantly in the severe group (p < .01). Severe patients also demonstrated higher scores on the Framingham stroke risk profile and lower Glasgow scores (p < .05). Furthermore, significant associations were noticed between stroke risk and age, blood cell count, neutrophil count, D-dimmer, and fibrin degradation productions (p < .05). CONCLUSIONS: Data suggested that coagulation functions were affected in patients with COVID-19. Hypercoagulable state in patients may lead to potential high risk of stroke.

Is Donated Breast Milk Better Than Formula for Feeding Very Low Birth Weight Infants? A Systematic Review and Meta-Analysis.

BACKGROUND: The role of donated breast milk and formula feeding in very low birth weight infants (VLBWIs) remains unclear. OBJECTIVE: The objective for this study was to evaluate the efficacy and safety of breast milk and formula for feeding VLBWIs. METHODS: A comprehensive search of PubMed databases was conducted on November 30, 2018, to identify related randomized controlled trials (RCTs). Pooled odds ratio (OR) and mean differences (MD) with 95% confidence intervals (CI) were calculated using either a fixed or random-effects model. RESULTS: Seven RCTs with a total of 876 infants were included. The formula showed more advantages in increasing infant weight (MD = -6.58, 95% CI: -11.19 to -1.98) and length (MD = -0.30, 95% CI: -0.41 to -0.20) than donated breast milk, but formula could also significantly increase the risks of necrotizing enterocolitis (OR = 0.33, 95% CI: 0.18 to 0.59) and length of hospital stay (MD = -3.78, 95% CI: -6.84 to -0.72) when compared with donated breast milk. No significant differences on the head circumference gain (MD = -0.16, 95% CI: -0.33 to 0.01), sepsis (OR = 1.21, 95% CI: 0.84 to 1.75), retinopathy of prematurity (OR = 1.22, 95% CI: 0.73 to 2.05) and mortality (OR = 0.84, 95% CI: 0.47 to 1.52) were found. LINKING EVIDENCE TO ACTION: The donated breast milk shows more advantages in reducing the incidence of NEC and length of hospital stay, but also more disadvantages in increasing the weight and length of VLBWIs and ELBWIs when compared with preterm formula feeding. Currently, there is no solid evidence demonstrating a significant advantage of donated breast milk over formula in the feeding of VLBWIs. Larger-scale RCTs with rigorous designs are needed to elucidate the feeding plans of VLBWIs.

Circ-HIPK3 Strengthens the Effects of Adrenaline in Heart Failure by MiR-17-3p - ADCY6 Axis.

Overactivation of ß-adrenergic receptor (ß-AR) can improve cardiac function temporarily but promotes the development and mortality of heart failure (HF) in the long run. CircRNA, a member of noncoding RNAs, can tolerate digestion of exonuclease and be a chronic stimulator to cell. But the relationship of circRNA with HF remains a puzzle and needs to be explored. Here, we found that circ-HIPK3 affected the concentration of Ca2+ in cytoplasm by miR-17-3p through ADCY6 (Adenylate cyclase type 6). The increase of ADCY6 caused by circ-HIPK3 was ameliorated by miR-17-3p overexpression and vice versa, implicating the existence of circ-HIPK3 - miR-17-3p - ADCY6 axis. And further assays showed that the level of circ-HIPK3 in heart was upregulated by adrenaline via transcription factor CREB1 (cAMP responsive element-binding protein 1). Experiments in vivo showed downregulation of circ-HIPK3 can alleviate fibrosis and maintain cardiac function post MI in mice. In conclusion, the increased circ-HIPK3 can be a helper for adrenaline but was harmful for heart in the long run and might be an ideal therapeutic target of HF.

RDM1 promotes neuroblastoma growth through the RAS-Raf-MEK-ERK pathway.

Neuroblastoma (NB) is an aggressive cancer that originates in the sympathetic nervous system and primarily affects children. Here, we show that high levels of RAD52 motif containing 1 (RDM1; a protein with similarities to RAD52, which is important for double-strand DNA repair) are associated with poor clinical outcomes for NB. In addition, RDM1-/- cells exhibited increased sensitivity to cisplatin, a common chemotherapy drug, and disruption of RDM1 suppressed NB cell proliferation. We also report that loss of RDM1 augmented cell apoptosis and induced cell cycle arrest, and that stable knockdown of RDM1 significantly inhibited NB tumor growth in a xenograft mouse model. Importantly, we identified that RDM1 promoted cell proliferation via the RAS-Raf-mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) signaling pathway. In conclusion, the current study demonstrates a correlation between DNA damage regulator RDM1 and the oncogenic RAS-Raf-MEK-ERK pathway in NB.

RETRACTED: Long non-coding RNA NEAT1 plays an important role in sepsis-induced acute kidney injury by targeting miR-204 and modulating the NF-κB pathway.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of authors with the approval of the Editor-in-Chief. Panel 'LPS+sh-NEAT1' from Figure 2C appears similar to panel 'si-PVT1' from Figure 2A of the article published by Wei Huang, Xiuwen Lan, Xueting Li, Dawei Wang, Yinghao Sun, Qian Wang, Hong Gao and Kaijiang Yu in the International Immunopharmacology 47 (2017) 134-140 http://dx.doi.org/10.1016/j.intimp.2017.03.030 and panel 'Control' from Figure 1D of the article published by Xiaodi Liu, Chengying Hong, Shipin Wu, Shiling Song, Zhi Yang, Lin Cao, Tongwei Song and Ying Yang in the Journal of Cellular Biochemistry 120 (2019) 11331-11341 https://doi.org/10.1002/jcb.28409. Given the comments of Dr Elisabeth Bik https://scienceintegritydigest.com/2020/02/21/the-tadpole-paper-mill/ regarding this article, the journal requested the corresponding author to provide the raw data. However, the author was not able to fulfil this request.