Suppression of lncRNA OIP5-AS1 Attenuates Apoptosis and Inflammation, and Promotes Proliferation by Mediating miR-25-3p Expression in Lipopolysaccharide-Induced Myocardial Injury.

Purpose: Long non-coding RNAs (LncRNAs) OIP5-AS1 and miR-25-3p play important roles in myocardial injury, whereas their roles in lipopolysaccharide (LPS)-induced myocardial injury remain unknown. The purpose of our study was to investigate the functional mechanisms of OIP5-AS1 and miR-25-3p in LPS-induced myocardial injury. Methods: Rats and H9C2 cells were treated with LPS to establish the model of myocardial injury in vivo and in vitro, respectively. The expression levels of OIP5-AS1 and miR-25-3p were determined by quantitative reverse transcriptase-polymerase chain reaction. Enzyme-linked immunosorbent assay was performed to measure the serum levels of IL-6 and TNF-α. The relationship between OIP5-AS1 and miR-25-3p/NOX4 was determined by luciferase reporter assay and/or RNA immunoprecipitation assay. The apoptosis rate was detected by flow cytometry, and cell viability was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. Western blot was performed to detect the protein levels of Bax, Bcl-2, caspase3, c-caspase3, NOX4, and p-NF-κB p65/NF-κB p65. Results: OIP5-AS1 was up-regulated, and miR-25-3p was down-regulated in myocardial tissues of LPS-induced rats and LPS-treated H9C2 cells. Knockdown of OIP5-AS1 relieved the myocardial injury in LPS-induced rats. Knockdown of OIP5-AS1 also inhibited the inflammation and apoptosis of myocardial cells in vivo, which was subsequently confirmed by in vitro experiments. In addition, OIP5-AS1 targeted miR-25-3p. MiR-25-3p mimics reversed the effects of OIP5-AS1 overexpression on promoting cell apoptosis and inflammation and on inhibiting cell viability. Besides, miR-25-3p mimics blocked the NOX4/NF-κB signalling pathway in LPS-induced H9C2 cells. Conclusion: Silencing of lncRNA OIP5-AS1 alleviated LPS-induced myocardial injury by regulating miR-25-3p.

CLINICAL AND PROGNOSTIC FEATURES OF CHRONIC CRITICAL ILLNESS/PERSISTENT INFLAMMATION IMMUNOSUPPRESSION AND CATABOLISM PATIENTS: A PROSPECTIVE OBSERVATIONAL CLINICAL STUDY.

ABSTRACT: Objective: The aims of this study were to investigate and compare the clinical features and prognosis of chronic critical illness (CCI)/persistent inflammation immunosuppression and catabolism (PICS). Methods: This is a prospective observational clinical study. During this study period, we collect intensive care unit patients' data from Suzhou Municipal Hospital and Suzhou Ninth People's Hospital. All patients older than 18 years were included, and according to the corresponding exclusion and diagnostic criteria, they were divided into four groups: PICS group, CCI group, CCI and PICS group (CCI + PICS), and neither CCI nor PICS group (NCCI + NPICS) and collected and recorded age, sex, hospital time, hospital diagnosis, Acute Physiology and Chronic Health Evaluation II score, Sequential Organ Failure Assessment score, C-reactive protein, absolute value lymphocyte count, serum albumin, white blood cell count, absolute value neutrophil count, secondary infection, and 28-day case fatality rate separately. Results: A total of 687 patients were admitted to the intensive care unit during the study period. The hospitalization time less than 14 days were excluded, and 168 patients were eventually included. There are 17 in the PICS group, 71 in the CCI group, 50 in the CCI + PICS group, and 30 in the NCCI + NPICS group. Baseline characteristics showed statistically significant differences in Sequential Organ Failure Assessment, length of hospital stay, and 28-day mortality among four groups. Baseline main indicator and multiple comparisons showed that the CCI + PICS group had longer hospital stay, worse prognosis, and more adverse outcomes. Multivariate analysis showed that final age, C-reactive protein on days 14 and 21, and serum albumin on days 1 and 21 had an impact on the prognosis ( P < 0.05). Conclusion: The clinical prognosis of the four groups decreased in order of NCCI + NPICS, CCI, PICS, and CCI + PICS. Our finding of clinically isolated PICS may indicate that PICS acts as an inducement or independent factor to worsen the prognosis of CCI.

Bone marrow mesenchymal stem cells attenuate LPS-induced acute lung injury in mice by promoting RvE1/ProD1 and modulating Treg/Th17 balance.

Acute lung injury (ALI) and its severe form acute respiratory distress syndrome (ARDS) are respiratory failures caused by excessive alveolar inflammation with high mortality. In this study, we investigated the effects of bone marrow mesenchymal stem cells (BMSCs) on lung injury of lipopolysaccharide (LPS)-induced ALI and explored the associated mechanisms. BMSCs were isolated, cultured, identified by staining with CD34 and CD44 surface markers. LPS-induced ALI mouse model was generated by injecting with LPS and divided into ALI group and ALI+BMSCs group. Mice treated without any reagents were assigned as Control, mice transplanted with BMSCs were assigned as BMSCs group. Regulatory T (Treg) and Th17 percentages were evaluated using flow cytometry. Proresolving mediators (resolvin E1 (RvE1), protectin D1 (ProD1)) in lung tissue and cytokines (interleukin-6 (IL-6) and IL-17) in serum were analyzed by ELISA. Myeloperoxidase (MPO) activity was determined. Cultured cells demonstrated typical characteristics of BMSCs. BMSCs transplantation (ALI+BMSCs) obviously alleviated LPS-induced ALI in mice. BMSCs transplantation significantly decreased MPO activity in LPS-induced ALI in mice compared to the Control group (p < 0.05). BMSCs transplantation markedly increased Treg percentages and decreased dendritic cells (DCs) and Th17 cells percentages compared to those of the Control group (p < 0.05). BMSCs transplantation remarkably enhanced RvE1 and ProD1 levels in LPS-induced ALI (ALI+BMSCs) compared to the ALI group (p < 0.05). BMSCs transplantation significantly attenuated IL-6 and IL-17 levels in serum of mice treated with LPS (ALI+BMSCs) compared to those of the ALI group (p < 0.05). In conclusion, BMSCs transplantation effectively attenuated LPS-induced pathological injury of ALI in mice, at least partly through promoting proresolving mediators RvE1 and ProD1 and modulating the balance of Treg/Th17.

Overview of the pathogenesis of COVID-19 (Review).

At present, the pathogenesis of the novel coronavirus disease 2019 (COVID-19) has not been fully elucidated. Clinical and experimental findings from studies investigating COVID-19 have suggested that the immune-inflammatory response has a crucial role in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The present article aimed to systematically review the available literature on the pathogenesis of COVID-19. Severe COVID-19 is characterized by organ dysfunction, hypercytokinemia and lymphopenia. It is assumed that the direct cytopathological damage of host cells and the dysregulated immune response caused by SARS-CoV-2 may be the primary underlying mechanisms of COVID-19. Based on the published literature, this review attempts to provide an integrated view of the immunological mechanisms and the potential pathogenesis of COVID-19, providing an in-depth summary of the host-pathogen interaction and host immune responses. It is of great importance to elucidate the possible pathogenesis of COVID-19 to determine the direction of future research.

Comparison of Biomechanical Characteristics and Pelvic Ring Stability Using Different Fixation Methods to Treat Pubic Symphysis Diastasis: A Finite Element Study.

The intention of this study was to compare the biomechanical characteristics using 5 internal fixation methods used clinically to stabilize a pubic symphysis diastasis (PSD, Tile type B1).A 3-dimensional finite element model of PSD was simulated using 5 implants, including single superior plate (Single-Plate), superior and anterior plate (Dual-Plate), single cannulated screw (Single-Screw), crossed dual cannulated screws (Cross-Screw), and parallel dual cannulated screws (Para-Screw). Three loads were distributed in all models, including dual-leg standing, single-leg stance, and rotation. To evaluate the biomechanical properties, the construct stiffness, the stress distribution, and the von Misses stress were recorded and analyzed. To evaluate pelvic ring stability, the micromotion of the pubic symphysis and iliosacral joint was analyzed.Disruption of pubic symphysis dramatically decreased the pelvic ring stability. Cross-screw and Para-Screw showed higher stiffness than other methods. All implants endured the maximum von Misses stress under single-leg stance. For Plate-Screw system, the maximum stress occurred at a place where it strides over pubic symphysis and adjacent Plate-Screw interface. The single implant and Para-Screw had a tendency to fail. Para-Screw showed the best fixation effect under dual-leg conditions. Cross-screw showed superior antishearing force capacity under single-leg stance. Dual-Plate provided maximum antihorizontal rotation. Para-Screw provided the maximum stabilization for the posterior pelvic ring.This study showed the biomechanical advantages of dual-implant for PSD only from the finite element view. The Para-Screw provided high construct stiffness under 3 load conditions. The single implant and Para-Screw had a tendency to fail. The better anterior and posterior pelvic stabilization were obtained by the dual-implant fixation than other methods. Therefore, the Cross-Screw and Dual-Plate fixation methods should be preferred in the treatment of pubic symphysis from the finite element view.