Survival study of enteral and parenteral nutrition pathways in critically ill patients receiving vasopressors: an analysis of the Medical Information Mart for Intensive Care-IV database.

This study compared survival outcomes between intensive care unit (ICU) patients receiving enteral nutrition (EN) and parenteral nutrition (PN) with vasopressor support, explored risk factors affecting clinical outcomes and established an evaluation model. Data from 1046 ICU patients receiving vasopressor therapy within 24 h from 2008 to 2019 were collected. Patients receiving nutritional therapy within 3 d of ICU admission were divided into EN or PN (including PN+EN) groups. Cox analysis and regression were used to determine relevant factors and establish a nomogram for predicting survival. The 28-d survival rate was significantly better in the EN group compared with the PN/PN+EN group. Risk factors included age, peripheral capillary oxygen saturation, red cell distribution width, international normalised ratio, potassium level, mean corpuscular Hg, myocardial infarction, liver disease, cancer status and nutritional status. The nomogram showed good predictive performance. In ICU patients receiving vasopressor drugs, patients receiving EN had a better survival rate than PN. Our nomogram had favourable predictive value for 28-d survival in patients. However, it needs further validation in prospective trials.

Circ_0018909 knockdown inhibits the development of pancreatic cancer via the miR-545-3p/FASN axis and reduces macrophage polarization to M2.

Multiple circular RNAs (circRNAs) were proven to regulate the development of pancreatic cancer. However, the action of circ_0018909 in pancreatic cancer was still unclear. The expression of circ_0018909, microRNA-545-3p (miR-545-3p), and fatty acid synthase (FASN) was measured using quantitative reverse-transcriptase PCR (qRT-PCR). Cell growth, cell cycle arrest, apoptotic cells, metastasis, and epithelial to mesenchymal transition (EMT) were determined using EdU assay, flow cytometry, wound-healing assay, transwell invasion, and western blotting, respectively. The expression of the macrophage markers, including CD80, MCP-1, iNOS, and IL-6 (M1 markers), as well as CD206 and CD163 (M2 markers), was analyzed using qRT-PCR. Circ_0018909 knockdown dramatically depressed cell growth, migration, invasion, EMT, and elevated the number of apoptotic cells in pancreatic cancer cells, and repressed tumor growth in mice. Moreover, we proved that the absence of miR-545-3p rescued the action of circ_0018909 downregulation on cell growth, metastasis, apoptosis, and EMT in pancreatic cancer cells. MiR-545-3p bound to FASN and FASN overexpression hindered the impacts of miR-545-3p on the progression of pancreatic cancer. Besides this, our data demonstrated that circ_0018909 induced polarization from M0 macrophages to M2 macrophages. Circ_0018909 knockdown retarded the development of pancreatic cancer by modulating miR-545-3p to regulate FASN expression.

Gracillin inhibits apoptosis and inflammation induced by lipopolysaccharide (LPS) to alleviate cardiac injury in mice via improving miR-29a.

Sepsis induces critical myocardial dysfunction, resulting in an increased mortality. Gracillin (GRA) is a natural steroidal saponin, showing strong capacities of anti-inflammation, but its pharmacological effects on lipopolysaccharide (LPS)-induced acute cardiac injury still remain unclear. In this study, we attempted to explore if GRA was effective to attenuate cardiac injury in LPS-challenged mice and the underlying mechanisms. First, we found that GRA treatments markedly up-regulated the expression of miR-29a in cardiomyocytes. LPS-induced cytotoxicity in cardiomyocytes was significantly alleviated by GRA treatment, as evidenced by the improved cell viability and reduced lactate dehydrogenase (LDH) release. In addition, LPS-triggered apoptotic cell death was clearly ameliorated in cardiomyocytes co-treated with GRA. Notably, LPS-exposed cells showed significantly reduced expression of miR-29a, while being rescued by GRA treatment. In vivo, LPS apparently impaired cardiac function in mice, which was, however, alleviated by GRA administration. In addition, GRA markedly attenuated apoptosis in hearts of LPS-challenged mice by decreasing the expression of cleaved Caspase-3. LPS-triggered inflammatory response in cardiac tissues was also suppressed by GRA through blocking nuclear factor κB (NF-κB) signaling pathway. We also found that miR-29a expression was highly reduced in hearts of LPS-treated mice but was rescued by GRA pretreatment. Besides, miR-29a mimic alleviated LPS-induced apoptosis and inflammation in cardiomyocytes; however, LPS-caused effects were further accelerated by miR-29a. Of note, the protective effects of GRA on LPS-injured cardiac tissues were significantly abrogated by miR-29a suppression. In conclusion, our findings demonstrated that GRA exerted an effective role against LPS-induced acute cardiac injury through impeding apoptosis and inflammation regulated by miR-29a.

Overexpression of GP73 promotes cell invasion, migration and metastasis by inducing epithelial-mesenchymal transition in pancreatic cancer.

Pancreatic cancer is one of the most difficult clinical cases to diagnose with a very low 5-year survival rate of 5%, regardless of the advances made in both the medical and surgical treatment of the disease. One of the contributing factors for the high mortality rate seen of pancreatic cancer patients is the lack of effective chemotherapies, which is believed to be due to drug-resistance. Based on recent evidence, epithelial-mesenchymal transition (ETM) of pancreatic cancer cells has been found to be associated with the development of drug resistance and an increase in cell invasion. Therefore, we conducted the present study in order to investigate the regulatory effects of Golgi protein-73 (GP73) on PC. GP73 and EMT-related gene expressions in PC, along with the adjacent and chronic pancreatitis tissues were determined by means of RT-qPCR and Western blot analysis. Cultured PC cells were treated with pAdTrack-CMV, si-NC, GP73 overexpression, Si-GP73, Snail-siRNA and GP73 + Snail-siRNA. Cell invasion, migration and metastasis were measured in vitro and in vivo. The results revealed that the PC tissues and chronic pancreatitis tissues exhibited diminished E-cadherin expression and amplified GP73, N-cadherin, Vimentin and Snail expression. In response to GP73 gene silencing, PC cells presented with increased E-cadherin expression and decreased N-cadherin, Vimentin, Snail expression in addition to the inhibition of the number of invasive cells, tumor volume and number of liver lesions. These findings highly indicated that the overexpression of GP73 promotes cell invasion, migration and metastasis by inducing EMT in PC.

JZL184 protects hippocampal neurons from oxygen-glucose deprivation-induced injury via activating Nrf2/ARE signaling pathway.

JZL184 is a selective inhibitor of monoacylglycerol lipase (MAGL) that has neuroprotective effect. However, the role of JZL184 in cerebral ischemia/reperfusion (I/R) injury and the exact mechanism have not been fully understood. This study was designed to elucidate the role of JZL184 in cerebral I/R injury induced by oxygen-glucose deprivation/reoxygenation (OGD/R) in hippocampal neurons. Hippocampal neurons were pretreated with various concentrations of JZL184 for 2 h, followed by OGD for 3 h and reoxygen for 24 h. Our results showed that JZL184 improved cell viability in hippocampal neurons in response to OGD/R. JZL184 treatment significantly inhibited the production of reactive oxygen species (ROS) and malondialdehyde (MDA), as well as increased superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities in OGD/R-induced hippocampal neurons. The increased TNF-α, IL-1ß, and IL-6 productions in OGD/R-induced hippocampal neurons were decreased after treatment with JZL184. Moreover, the OGD/R-caused intense TUNEL staining in hippocampal neurons was attenuated by JZL184. JZL184 treatment prevented OGD/R-caused increases in bax and cleaved caspase-3 expression and a decrease in bcl-2 expression. Furthermore, JZL184 treatment significantly promoted the activation of Nrf2/ARE signaling pathway in OGD/R-induced hippocampal neurons. Additionally, silencing of Nrf2 reversed the protective effect of JZL184 on hippocampal neurons under OGD/R condition. Taken together, these findings suggested that JZL184 exerted protective effect against OGD/R-induced injury in hippocampal neurons via activating Nrf2/ARE signaling pathway, which provided in vitro experimental support for the therapeutic benefit of JZL184 in cerebral ischemia.

Folic acid (FA)-conjugated mesoporous silica nanoparticles combined with MRP-1 siRNA improves the suppressive effects of myricetin on non-small cell lung cancer (NSCLC).

Non-small cell lung cancer (NSCLC) is a common diagnosed cancer disease worldwide and its management remains a challenge. Synergistic cancer therapeutic strategy is interesting for multiple advantages, such as excellent targeting accuracy, low side effects, and promoted therapeutic efficiency. In the present study, myricetin (Myr)-loaded mesoporous silica nanoparticles (MSN) combined with multidrug resistance protein (MRP-1) siRNA was prepared. The surface of the synthesized nanoparticles was modified with folic acid (FA) to promote the therapeutic efficiency of Myr for the treatment of NSCLC. The collected particles were nano-sized and showed a sustained release of Myr in the physiological conditions. FA-conjugated nanoformulations displayed a significant uptake in lung cancer cells compared with that of the non-targeted nanoparticles. The in vitro drug release results suggested a sustained release in FA-conjugated MSN with Myr and MRP-1 nanoparticles compared to the free Myr and MSN combined with MRP-1/Myr. Treatments with FA-conjugated MSN combined with Myr and MRP-1 markedly reduced the cell viability of lung cancer cell lines, including A549 and NCI-H1299, which was accompanied with the decreased number of colony formation. In addition, FA-conjugated MSN loaded with Myr and MRP-1 significantly induced apoptosis in lung cancer cells, along with up-regulated expression levels of cleaved Caspase-3 and PARP. In vivo fluorescence results demonstrated that FA-conjugated MSN with Myr and MRP-1 nanoparticles could specifically accumulate at tumor sites. Compared with free Myr and MSN combined with MRP-1/Myr nanoparticles, FA-conjugated MSN loaded with Myr and MRP-1 nanoparticles could more effectively suppress tumor growth with little side effects. Overall, FA-conjugated nanoparticulate system could provide a novel and effective platform for the treatment of NSCLC.

[Predictive value of neutrophil to lymphocyte ratio on 28-day mortality of patients with severe pneumonia].

OBJECTIVE: To evaluate the predictive value of neutrophil to lymphocyte ratio (NLR) on 28-day mortality of patients with severe pneumonia. METHODS: The clinical data of 214 severe pneumonia patients admitted to the department of emergency medicine of the First Affiliated Hospital of Xi'an Jiao Tong University from January 2015 to December 2018 were retrospectively analyzed. The clinical parameters, such as gender, age, underlying diseases, and blood routine, procalcitonin (PCT), liver and kidney function, blood lactic acid (Lac), arterial partial pressure of oxygen (PaO2) at admission or within 24 hours after admission were reviewed. NLR, oxygenation index (PaO2/FiO2) and acute physiology and chronic health evaluation II (APACHE II) were calculated, and the change tendency of each index within 3 days after admission were observed. The patients were divided into survival group and death group according to 28-day outcomes. Multivariate Logistic regression analysis was used to screen the high risk factors of 28-day mortality in patients with severe pneumonia. Receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of NLR for 28-day mortality risk in patients with severe pneumonia. RESULTS: 214 patients were enrolled in the analysis, 132 survived in 28 days and 82 died. Compared with survival group, the white blood cell (WBC), neutrophil (NEU), NLR, PCT, Lac and APACHE II scores were significantly increased, and lymphocyte (LYM) was significantly decreased in the death group. There was no significant difference in gender, age, basic diseases, platelet count (PLT), liver and kidney function parameters, or PaO2/FiO2 between the two groups. The NLR, PCT, Lac and APACHE II score in the death group were increased gradually within 3 days after admission, PaO2/FiO2 was decreased gradually, which showed significant differences as compared with survival group at 3 days after admission [NLR: 27.15±7.61 vs. 14.66±4.83, PCT (µg/L): 13.52±3.22 vs. 6.41±4.22, Lac (mmol/L): 6.78±1.70 vs. 2.74±1.15, APACHE II score: 37.76±5.30 vs. 22.11±4.94, PaO2/FiO2 (mmHg, 1 mmHg = 0.133 kPa): 114.12±20.16 vs. 186.49±13.95, all P < 0.05]. Multiple Logistic regression analysis showed that NLR [odds ratio (OR) = 1.163, 95% confidence interval (95%CI) = 1.007-1.343, P = 0.040], PCT (OR = 1.210, 95%CI = 1.098-1.333, P = 0.001), Lac (OR = 1.263, 95%CI = 1.011-1.579, P = 0.040) and APACHE II score (OR = 1.103, 95%CI = 1.032-1.179, P = 0.004) were the independent risk factors of 28-day mortality in the patients with severe pneumonia. ROC curve analysis showed that compared with the traditional indicators including PCT, Lac, and APACHE II score, NLR showed a good predictive value for 28-day mortality in the patients with severe pneumonia [area under ROC curve (AUC): 0.791 vs. 0.707, 0.690, 0.720]. When the optimal cut-off value of NLR was 14.92, the sensitivity was 71.95% and the specificity was 73.48%, meanwhile, the positive likelihood ratio was 2.713 and the negative likelihood ratio was 0.382. CONCLUSIONS: The increased NLR at admission is a high risk factor of 28-day mortality in patients with severe pneumonia, which is useful for predicting prognosis of patients with severe pneumonia.

Deoxycholic acid induces the overexpression of intestinal mucin, MUC2, via NF-kB signaling pathway in human esophageal adenocarcinoma cells.

BACKGROUND: Mucin alterations are a common feature of esophageal neoplasia, and alterations in MUC2 mucin have been associated with tumor progression in the esophagus. Bile acids have been linked to esophageal adenocarcinoma and mucin secretion, but their effects on mucin gene expression in human esophageal adenocarcinoma cells is unknown. METHODS: Human esophageal adenocarcinoma cells were treated 18 hours with 50-300 muM deoxycholic acid, chenodeoxycholic acid, or taurocholic acid. MUC2 transcription was assayed using a MUC2 promoter reporter luciferase construct and MUC2 protein was assayed by Western blot analysis. Transcription Nuclear factor-kappaB activity was measured using a Nuclear factor-kappaB reporter construct and confirmed by Western blot analysis for Nuclear factor-kappaB p65. RESULTS: MUC2 transcription and MUC2 protein expression were increased four to five fold by bile acids in a time and dose-dependent manner with no effect on cell viability. Nuclear factor-kappaB activity was also increased. Treatment with the putative chemopreventive agent aspirin, which decreased Nuclear factor-kappaB activity, also decreased MUC2 transcription. Nuclear factor-kappaB p65 siRNA decreased MUC2 transcription, confirming the significance of Nuclear factor-kappaB in MUC2 induction by deoxycholic acid. Calphostin C, a specific inhibitor of protein kinase C (PKC), greatly decreased bile acid induced MUC2 transcription and Nuclear factor-kappaB activity, whereas inhibitors of MAP kinase had no effect. CONCLUSION: Deoxycholic acid induced MUC2 overexpression in human esophageal adenocarcinoma cells by activation of Nuclear factor-kappaB transcription through a process involving PKC-dependent but not PKA, independent of activation of MAP kinase.

[Role of bile in rat gastric mucosal injury due to duodenogastric reflux].

OBJECTIVE: To explore the effect of bile in inducing gastric mucosal injury in rats. METHODS: SD rats were divided into 4 groups, namely bile duct ligation group, duodenogastric reflux (DGR) group, DGR plus bile duct ligation group and normal control group. The pathological changes in the gastric mucosa and tight junction 3 months after gastrojejunostomy were observed and compared with the findings in the normal control rats. RESULTS: Compared with the rats in DGR plus bile duct ligation group, the rats in DGR group showed obvious gastric mucosal hyperemia, foveolar hyperplasia and severely impaired tight junction between the gastric mucosal cells. CONCLUSION: Bile plays an important role in gastric mucosal injury due to DGR.