BackgroundHeme oxygenase-1 (HO-1) is an inducible defense gene which plays a significant role in inflammation. HO-1 protects cells and tissues through the mechanism of anti-oxidation, maintaining microcirculation and anti-inflammation. The aim of the current study is to investigate the role of HO-1 on systemic inflammatory response in severe acute pancreatitis (SAP).MethodsForty male Sprague-Dawley (SD) rats were randomly assigned into four groups: control group (n = 10); SAP group (n = 10), SAP model was induced by retrograde injection of 3% sodium taurocholate through pancreatic duct; HO-1 stimulation group (n = 10), SD rats were injected 75 μg/kg hemin intraperitoneally 30 min after induction of SAP; HO-1 inhibition group (n = 10), SD rats were injected 20 μg/kg Zinc porphyrin (Zn-PP) intraperitoneally 30 min after induction of SAP. After 24 h of SAP establishment, tissues were collected for HO-1, tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) mRNA expression, and blood samples were collected for cytokines and biochemical measurements. Meanwhile, the histopathological changes of pancreas and liver tissues were observed.ResultsThe expression of HO-1 mRNA and protein were significantly induced by SAP in rat pancreas and liver. Hemin treatment significantly decreased oxidative stress and TNF-α in plasma and tissues, while the IL-10 was significantly increased. Pancreas and liver injury induced by SAP was markedly attenuated by Hemin treatment. Moreover, inhibition of HO-1 expression by Zn-PP administration aggravated the injury caused by SAP.ConclusionsInduction of HO-1 in early SAP may modulate systemic inflammatory response and prevent pancreas and nearby organs such as liver injury through inhibition of TNF-α and augmentation of IL-10.
A novel approach for fast generation of video holograms of three-dimensional (3-D) moving objects using a motion compensation-based novel-look-up-table (MC-N-LUT) method is proposed. Motion compensation has been widely employed in compression of conventional 2-D video data because of its ability to exploit high temporal correlation between successive video frames. Here, this concept of motion-compensation is firstly applied to the N-LUT based on its inherent property of shift-invariance. That is, motion vectors of 3-D moving objects are extracted between the two consecutive video frames, and with them motions of the 3-D objects at each frame are compensated. Then, through this process, 3-D object data to be calculated for its video holograms are massively reduced, which results in a dramatic increase of the computational speed of the proposed method. Experimental results with three kinds of 3-D video scenarios reveal that the average number of calculated object points and the average calculation time for one object point of the proposed method, have found to be reduced down to 86.95%, 86.53% and 34.99%, 32.30%, respectively compared to those of the conventional N-LUT and temporal redundancy-based N-LUT (TR-N-LUT) methods.
A new robust MPEG-based novel look-up table (MPEG-NLUT) is proposed for accelerated computation of video holograms of fast-moving three-dimensional (3-D) objects in space. Here, the input 3-D video frames are sequentially grouped into sets of four, in which the first and remaining three frames in each set become the reference (RF) and general frames (GFs). Then, the frame images are divided into blocks, from which motion vectors are estimated between the RF and each of the GFs, and with these estimated motion vectors, object motions in all blocks are compensated. Subsequently, only the difference images between the motion-compensated RF and each of the GFs are applied to the NLUT for CGH calculation based on its unique property of shift-invariance. Experiments with three types of test 3-D video scenarios confirm that the average number of calculated object points and the average calculation time of the proposed method, have found to be reduced down to 27.34%, 55.46%, 45.70% and 19.88%, 44.98%, 30.72%, respectively compared to those of the conventional NLUT, temporal redundancy-based NLUT (TR-NLUT) and motion compensation-based NLUT (MC-NLUT) methods.
Inflammation has been implicated in myocardial infarction (MI). MDM2 associates with nuclear factor-κB (NF-κB)-mediated inflammation. However, the role of MDM2 in MI remains unclear. This study aimed to evaluate the impacts of MDM2 inhibition on cardiac dysfunction and fibrosis after experimental MI and the underlying mechanisms. Three-month-old male C57BL/6 mice were subjected to left anterior descending (LAD) coronary artery ligation for induction of myocardial infarction (MI). Immediately after MI induction, mice were treated with Nutlin-3a (100 mg/kg) or vehicle twice daily for 4 weeks. Survival, heart function and fibrosis were assessed. Signaling molecules were detected by Western blotting. Mouse myofibroblasts under oxygen and glucose deprivation were used for in vitro experiments. MDM2 protein expression was significantly elevated in the mouse heart after MI. Compared with vehicle-treated animals, Nutlin-3a treatment reduced the mouse mortality. Nutlin-3a treatment improved heart function and decreased the infarct scar and fibrosis compared with vehicle. Furthermore, MDM2 inhibition restored IκB and inhibited NF-κB activation, leading to suppressed production of proinflammatory cytokines in the heart after MI. The consistent results were obtained in vitro. MDM2 inhibition reduced cardiac dysfunction and fibrosis after MI. These effects of MDM2 inhibition is mediated through modulating NF-κB activation, resulting in inhibition of inflammatory response.
Objective
Coronavirus disease 2019 (COVID-19) is a major challenge facing the world. Certain guidelines issued by National Health Commission of the People's Repubilic of China recommend intravenous immunoglobulin (IVIG) for adjuvant treatment of COVID-19. However, there is a lack of clinical evidence to support the use of IVIG.
Methods
This single-center retrospective cohort study included all adult patients with laboratory-confirmed severe COVID-19 in the Respiratory and Critical Care Unit of Dabie Mountain Regional Medical Center, China. Patient information, including demographic data, laboratory indicators, the use of glucocorticoids and IVIG, hospital mortality, the application of mechanical ventilation, and the length of hospital stay was collected. The primary outcome was the composite end point, including death and the use of mechanical ventilation. The secondary outcome was the length of hospital stay.
Results
Of the 285 patients with confirmed COVID-19, 113 severely ill patients were included in this study. Compared to the non-IVIG group, more patients in the IVIG group reached the composite end point [12 (25.5%) vs 5 (7.6%), P = 0.008] and had longer hospital stay periods [23.0 (19.0–31.0) vs 16.0 (13.8–22.0), P < 0.001]. After adjusting for confounding factors, differences in primary outcomes between the two groups were not statistically significant (P = 0.167), however, patients in the IVIG group had longer hospital stay periods (P = 0.041).
Conclusion
Adjuvant therapy with IVIG did not improve in-hospital mortality rates or the need for mechanical ventilation in severe COVID-19 patients. Our study does not support the use of immunoglobulin in patients with severe COVID-19 patients.
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