Acute lung injury (ALI) / acute respiratory distress syndrome (ARDS) is a critical clinical syndrome with complex pathology and pathogenesis. Since there is no specific treatment for ALI, it is ...important to study the mechanism of how ALI develop. Sestrin2 (Sesn2) plays a critical role in the regulation of cellular stress response and oxidant defense. However, the potential function of Sesn2 in ALI/ARDS and the associated mechanism remains unclear.
Lipopolysaccharide (LPS) induced ALI model was performed in the wild-type and Sesn2 knockout (Sesn2−/−) mice. The nod-like receptor protein 3 (NLRP3) inflammasome, cell pyroptosis and mitophagy were detected by western blots, immunofluorescent staining, flow cytometry. Lung injury were measured by histopathology and electron microscopy.
Knockout of Sesn2 enhanced LPS-induced ALI. As detailed in Sesn2−/− mice, NLRP3 inflammasome and cell pyroptosis were increased in lungs; IL-1β and IL-18 in serum and bronchoalveolar lavage fluid (BALF) were further promoted; In the isolated alveolar macrophages from Sesn2−/− mice, mitophagy induced by LPS was markedly inhibited, while reactive oxygen species (ROS), mitochondrial damage and cell pyroptosis were enhanced. Knocking down or overexpressing Sensn2 in J774.A1 cells demonstrated Sesn2 promoted Sequestosome1 (SQSTM1) expression and mitophagy by PTEN-induced putative kinase 1 (Pink1)/Parkin pathway.
Sesn2 protected ALI by promoting mitophagy that exerts protection of AMs pyroptosis and negative regulation of NLRP3 inflammasomes. These data indicated Sesn2 might be a potential target for ALI treatment.
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. Because of the novelty ...of the virus, there are currently no SARS-CoV-2-specific treatments or vaccines available. Therefore, rapid development of effective vaccines against SARS-CoV-2 are urgently needed. Here, we developed a pilot-scale production of PiCoVacc, a purified inactivated SARS-CoV-2 virus vaccine candidate, which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats, and nonhuman primates. These antibodies neutralized 10 representative SARS-CoV-2 strains, suggesting a possible broader neutralizing ability against other strains. Three immunizations using two different doses, 3 or 6 micrograms per dose, provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without observable antibody-dependent enhancement of infection. These data support the clinical development and testing of PiCoVacc for use in humans.
Gliomas are the most common primary central nervous system tumors, with a high mortality rate. Early and accurate diagnosis of gliomas is critical for successful treatment. Biosensors are significant ...in the detection of molecular biomarkers because they are simple to use, portable, and capable of real-time analysis. This review discusses several important molecular biomarkers as well as various biosensors designed for glioma diagnosis, such as electrochemical biosensors and optical biosensors. We present our perspectives on the existing challenges and hope that this review can promote the improvement of biosensors.
Hospital crowding is a rising problem, effective predicting and detecting managment can helpful to reduce crowding. Our team has successfully proposed a hybrid model combining both the autoregressive ...integrated moving average (ARIMA) and the nonlinear autoregressive neural network (NARNN) models in the schistosomiasis and hand, foot, and mouth disease forecasting study. In this paper, our aim is to explore the application of the hybrid ARIMA-NARNN model to track the trends of the new admission inpatients, which provides a methodological basis for reducing crowding.
We used the single seasonal ARIMA (SARIMA), NARNN and the hybrid SARIMA-NARNN model to fit and forecast the monthly and daily number of new admission inpatients. The root mean square error (RMSE), mean absolute error (MAE) and mean absolute percentage error (MAPE) were used to compare the forecasting performance among the three models. The modeling time range of monthly data included was from January 2010 to June 2016, July to October 2016 as the corresponding testing data set. The daily modeling data set was from January 4 to September 4, 2016, while the testing time range included was from September 5 to October 2, 2016.
For the monthly data, the modeling RMSE and the testing RMSE, MAE and MAPE of SARIMA-NARNN model were less than those obtained from the single SARIMA or NARNN model, but the MAE and MAPE of modeling performance of SARIMA-NARNN model did not improve. For the daily data, all RMSE, MAE and MAPE of NARNN model were the lowest both in modeling stage and testing stage.
Hybrid model does not necessarily outperform its constituents' performances. It is worth attempting to explore the reliable model to forecast the number of new admission inpatients from different data.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Emerging evidence has shown that dysregulation function of long non-coding RNAs (lncRNAs) implicated in gastric cancer (GC). However, the role of the differentially expressed lncRNAs in GC has not ...fully explained.
LncRNA expression profiles were determined by lncRNA microarray in five pairs of normal and GC tissues, further validated in another 75 paired tissues by quantitative real-time PCR (qRT-PCR). Overexpression of lncRNA MT1JP was conducted to assess the effect of MT1JP in vitro and in vivo. The biological functions were demonstrated by luciferase reporter assay, western blotting and rescue experiments.
LncRNA MT1JP was significantly lower in GC tissues than adjacent normal tissues, and higher MT1JP was remarkably related to lymph node metastasis and advance stage. Besides, GC patients with higher MT1JP expression had a well survival. Functionally, overexpression of lncRNA MT1JP inhibited cell proliferation, migration, invasion and promoted cell apoptosis in vitro, and inhibited tumor growth and metastasis in vivo. Functional analysis showed that lncRNA MT1JP regulated FBXW7 expression by competitively binding to miR-92a-3p. MiR-92a-3p and down-regulated FBXW7 reversed cell phenotypes caused by lncRNA MT1JP by rescue analysis.
MT1JP, a down-regulated lncRNA in GC, was associated with malignant tumor phenotypes and survival of GC. MT1JP regulated the progression of GC by functioning as a competing endogenous RNA (ceRNA) to competitively bind to miR-92a-3p and regulate FBXW7 expression. Our study provided new insight into the post-transcriptional regulation mechanism of lncRNA MT1JP, and suggested that MT1JP may act as a potential therapeutic target and prognosis biomarker for GC.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Photo-labile molecules have been widely used not only in organic synthesis but also in biological study. The chemistry of the typical photo-labile organic molecules, including their structure, ...mechanism underlying their photo-lability and strategies to integrate them with biomolecules, is reviewed to illustrate the structural basis for photo-activable caged compounds. Biological applications of representative photo-labile caged molecules were also illustrated for a general understanding on the important roles of caged compounds in dynamic biological studies. This tutorial review would provide an interdisciplinary overview on the important area of chemical biological study making use of photo-labile caged compounds.
Neutrophil extracellular traps (NETs) facilitate the extracellular killing of pathogens. However, excessive NETs formation and poor degradation are associated with exacerbated immune responses and ...tissue injury. In this study, we investigated the role of NETs in lipopolysaccharide (LPS)-mediated acute lung injury (ALI) and assessed the use of DNase I, for the treatment of ALI. Additionally, we focused on the controversial issue of whether LPS directly induces NETs release in vitro. NETs formation was detected in murine ALI tissue in vivo and was associated with increased NETs markers, citrullinated-histone H3 tissue levels and NET-DNA levels in BALF. Treatment with DNase I significantly degraded NETs and reduced citrullinated-histone H3 levels, which protected against ALI and ameliorated pulmonary oedema and total protein in BALF. In addition, DNase I significantly reduced IL-6 and TNF-α levels in plasma and BALF. In vitro, LPS-activated platelets rather than LPS alone efficiently induced NETs release. In conclusion, NETs formed during LPS-induced ALI, caused organ damage and initiated the inflammatory response. NETs degradation by DNase I promoted NET-protein clearance and protected against ALI in mice; thus, DNase I may be a new potential adjuvant for ALI therapy. Specifically, LPS induced NETs formation in an indirect manner via platelets activation.
Abstract Diabetic cardiomyopathy is a specific type of cardiomyopathy. In DCM, glucose uptake and utilization are impaired due to insulin deficiency or resistance, and the heart relies more heavily ...on fatty acid oxidation for energy, resulting in myocardial lipid toxicity-related injury. MARK4 is a member of the AMPK-related kinase family, and improves ischaemic heart failure through microtubule detyrosination. However, the role of MARK4 in cardiac regulation of metabolism is unclear. In this study, after successful establishment of a diabetic cardiomyopathy model induced by streptozotocin and a high-fat diet, MARK4 expression was found to be significantly increased in STZ-induced DCM mice. After AAV9-shMARK4 was administered through the tail vein, decreased expression of MARK4 alleviated diabetic myocardial damage, reduced oxidative stress and apoptosis, and facilitated cardiomyocyte mitochondrial fusion, and promoted myocardial lipid oxidation metabolism. In addition, through the RNA-seq analysis of differentially expressed genes, we found that MARK4 deficiency promoted lipid decomposition and oxidative metabolism by downregulating the expression of ACSL4, thus reducing myocardial lipid accumulation in the STZ-induced DCM model.
Hydrogen sulfide (H
S) is involved in cancer biological processes. However, there are several controversies concerning the role of H
S in cancer development and progression. In this study, we found ...that the growth and migration of hepatocellular carcinoma (HCC) cells were enhanced by 10-100 μM NaHS and dose-dependently inhibited by 600-1000 μM NaHS. The apoptotic levels were reduced by 25-100 μM NaHS but increased by 400-1000 μM NaHS in HCC cells. After treatment with 25-50 μM NaHS, the protein levels of p-EGFR, p-ERK, MMP-2, and p-AKT were increased, whereas the levels of PTEN and the ratio of BAX/BCL-2 were down-regulated. Administration of 800-1000 μM NaHS showed opposite effects on these protein levels in HCC cells. However, H
S showed no effects on the growth, migration, apoptosis, and the protein levels of the EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways in L02 cells. Furthermore, 25-100 μM NaHS promoted HCC tumor growth and blood vessel formation, while 800-1000 μM NaHS inhibited angiogenesis and tumor growth with no obvious systemic toxicity. These results indicate that H
S acts as a double-edged sword in HCC cells through EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways. Novel H
S donors could be designed and applied for further antitumor research.
Ischemia-reperfusion (I/R) injury is one of the major causes of high morbidity, disability, and mortality in the world. I/R injury remains a complicated and unresolved situation in clinical practice, ...especially in the field of solid organ transplantation. Hydrogen sulfide (H2S) is the third gaseous signaling molecule and plays a broad range of physiological and pathophysiological roles in mammals. H2S could protect against I/R injury in many organs and tissues, such as heart, liver, kidney, brain, intestine, stomach, hind-limb, lung, and retina. The goal of this review is to highlight recent findings regarding the role of H2S in I/R injury. In this review, we present the production and metabolism of H2S and further discuss the effect and mechanism of H2S in I/R injury.
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