Background The purpose of the present study was to investigate the effect of erythropoietin (EPO) on lung ischemia-reperfusion injury (LIRI). Methods Sprague Dawley rats and BEAS-2B cells were employed to construct an ischemia-reperfusion (I/R)-induced model in vivo and in vitro, respectively. Afterward, I/R rats and tert-butyl hydroperoxide (TBHP)-induced cells were treated with different concentrations of EPO. Furthermore, 40 patients with LIRI and healthy controls were enrolled in the study. Results It was observed that lung tissue damage, cell apoptosis and the expression of BAX and caspase-3 were higher in the LIRI model in vivo and in vitro than in the control group, nevertheless, the Bcl-2, FGF23 and FGFR4 expression level was lower than in the control group. EPO administration significantly reduced lung tissue damage and cell apoptosis while also up-regulating the expression of FGF23 and FGFR4. Rescue experiments indicated that EPO exerted a protective role associated with the FGF23/FGFR4/p-ERK1/2 signal pathway. Notably, the expression of serum EPO, FGF23, FGFR4 and Bcl-2 was decreased in patients with LIRI, while the expression of caspase-3 and BAX was higher. Conclusion EPO could effectively improve LIRI, which might be related to the activation of the FGF23/FGFR4/p-ERK1/2 signaling pathway.

BACKGROUNDAsthma is a heterogeneous and complex chronic airway disease with a high incidence rate, characterized by chronic airway inflammation. Although the anti-inflammatory effect of zeaxanthin has been demonstrated in various disease models, its explicit role in allergic asthma remains elusive.METHODSAn allergic asthma model was established by ovalbumin (OVA) stimulation in BALB/c nude mice. The pathological examination, collagen deposition and expression of α-smooth muscle actin (α-SMA) in lung tissues were determined by hematoxylin and eosin (H&E), MASSON and immunofluorescence staining, respectively. Besides, the effect of zeaxanthin on inflammation and oxidative stress was assessed by the enzyme-linked immunosorbent assay (ELISA) and spectrophotometry measure. Moreover, the underlying mechanism was analyzed by detecting the expression of phosphorylated p38 (p-p38), p38, β-catenin, p-c-Jun N-terminal kinase (p-JNK) and JNK with western blot assays.RESULTSThe distinct infiltration of inflammatory cells was observed in the OVA-induced asthma mice model with significantly increased concentrations of immunoglobulin E (IgE), interleukin-4 (IL-4), IL-5, IL-13 and eotaxin (p˂0.001), which were prominently reversed by zeaxanthin treatment (p˂0.001). In addition, zeaxanthin treatment decreased the OVA-induced collagen deposition and α-SMA expression. A similar inhibitory effect of zeaxanthin on the oxidative stress was also observed in the OVA-induced asthma mice model, as evidenced by the prominent decrease of malondialdehyde (MDA) concentration and the remarkable increase of superoxide dismutase (SOD), glutathione S transferase (GST) and Glutathione (GSH) concentrations (p˂0.001). Moreover, zeaxanthin introduction markedly reduced the relative expressions of p-p38/p38, β-catenin and p-JNK/JNK in the OVA-induced asthma mice model (p˂0.001), indicating that zeaxanthin suppressed the p38 mitogen-activated protein kinase (p38 MAPK)/β-catenin signaling pathway in the OVA-induced asthma mice model.CONCLUSIONSZeaxanthin attenuated OVA-induced allergic asthma in mice via modulating the p38 MAPK/β-catenin signaling pathway.

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) causing Bloodstream infection (BSI) are associated with high rates of mortality. Nevertheless, only a few studies regarding the epidemiology of CRKP BSI in south China. The purpose of this study was to describe the epidemiology, clinical characteristics, and the mortality of risk factors associated with CRKP causing bloodstream infection. Methods: A retrospective study of patients with CRKP BSI was recruited from teaching hospital in south China from January 2016 to December 2018. Clinical data were collected from medical records. Results: In total, 90 patients with CRKP BSI were enrolled in the study, while 57% (51/90) of the CRKP BSI were obtained from ICU. Most CRKP BSIs originated from hospitals (81; 85%), while the rest (9; 10%) were healthcare-associated. In univariate analysis, gastrointestinal hemorrhage (p=0.029), Pitt bacteremia score (P=0.045), Charlson comorbidity index (p=0.018) and Corticosteroids use (p=0.036) and Septic shock (p=0.001) were associated with the risk factors for mortality. In a multivariate analysis, septic shock (adjusted odds ratio [aOR] 5.591, 95% confidence interval [CI] 1.405-22.246, P=0.015) and Corticosteroids use (aOR 4.148, 95% CI 1.331-12.928, P=0.014) were independently predictors of mortality. Conclusion: Our data showed that the morbidity and mortality of CRKP BSIs patient from ICU and non-ICU was no significant difference. Standardizing operation and improving nurse quality may play an important role in CRKP BSI patient in intensive care unit. Septic shock and Corticosteroids use were the independent factors of CRKP BSI patient mortality. However, the study did not show an association between invasive procedures and the development of CRKP BSI.

Abstract Objective: Our aim was to investigate the effect of emodin on intestinal and lung injury induced by acute intestinal injury in rats and explore potential molecular mechanisms. Methods: Healthy male Sprague–Dawley (SD) rats were randomly divided into five groups (n=10, each group): normal group; saline group; acute intestinal injury model group; model + emodin group; model+NF-κB inhibitor pynolidine dithiocarbamate (PDTC) group. Histopathological changes in intestine/lung tissues were observed by Hematoxylin and Eosin (H&E) and terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling (TUNEL) staining. Serum IKBα, p-IKBα, surfactant protein-A (SP-A) and toll-like receptor 4 (TLR4) levels were examined using enzyme-linked immunosorbent assay (ELISA). RT-qPCR was performed to detect the mRNA expression levels of IKBα, SP-A and TLR4 in intestine/lung tissues. Furthermore, the protein expression levels of IKBα, p-IKBα, SP-A and TLR4 were detected by Western blot. Results: The pathological injury of intestinal/lung tissues was remarkedly ameliorated in models treated with emodin and PDTC. Furthermore, the intestinal/lung injury scores were significantly decreased after emodin or PDTC treatment. TUNEL results showed that both emodin and PDTC treatment distinctly attenuated the apoptosis of intestine/lung tissues induced by acute intestinal injury. At the mRNA level, emodin significantly increased the expression levels of SP-A and decreased the expression levels of IKBα and TLR4 in intestine/lung tissues. According to ELISA and Western blot, emodin remarkedly inhibited the expression of p-IKBα protein and elevated the expression of SP-A and TLR4 in serum and intestine/lung tissues induced by acute intestinal injury. Conclusion: Our findings suggested that emodin could protect against intestinal and lung injury induced by acute intestinal injury by modulating SP-A and TLR4/NF-κB pathway.

Ubiquitin C‐terminal hydrolase‐L3 (UCH‐L3) is a deubiquitinase that has a crucial role in oncogenesis. This study was aimed to explore the biological function of UCH‐L3 in non‐small cell lung cancer (NSCLC). Bioinformatics analysis was used to detect UCH‐L3 expression in NSCLC tissues and normal lung tissues, and to analyze the relationship between UCH‐L3 expression and survival of patients. qRT‐PCR and western blotting assays were used to detect UCH‐L3 expression in NSCLC tumor tissues and adjacent normal tissues. CCK‐8 assay was performed to examine the effect of UCH‐L3 on NSCLC cell proliferation. Flow cytometry assay was conducted to examine the effect of UCH‐L3 on NSCLC cell cycle and apoptosis. The expression of UCH‐L3 in NSCLC tissues was markedly higher than in normal lung tissues, and high expression of UCH‐L3 was positively associated with the poor survival of patients. UCH‐L3 knockdown significantly inhibited the proliferation of NSCLC cells, whereas UCH‐L3 overexpression had the opposite effect. Moreover, UCH‐L3 promoted NSCLC cells proliferation via accelerating cell cycle and inhibiting cell apoptosis. UCH‐L3 is upregulated in NSCLC and positively associated with the poor survival, and its expression contributes to NSCLC cell proliferation by accelerating cell cycle and inhibiting cell apoptosis.

AIMS:Endotoxin induced acute lung injury (ALI) is a critical complication of some clinical illnesses. Endothelial cell dysfunction and excessive pro-inflammation cytokine release are pivotal to the injury of alveolar-capillary membrane which is the typical characteristic of endotoxic lung injury. As a potential marker of endothelial cells, endocan plays an important role in many endothelial-dependent pathophysiological diseases. We speculated that endocan have anti-inflammatory property in ALI. Here, we investigated the role of endocan in LPS-induced ALI.MATERIALS AND METHODS:Mice were randomly divided into 4 groups. LPS were used to construct ALI mice model by aerosolization for 20 min. Endocan was intraperitoneal injected at 30 min before LPS exposure. Levels of TNF-α, IFN-γ, IL-1β, IL-6 and MPO activities were detected by indicated ELISA. Cell apoptotic rate was determined by Annexin V/PI kit, ROS level and MPTP were detected by DCFH-DA and JC-1 kit, respectively. Seahorse XF96 was applied to evaluate the alteration of OCR and ECAR. Western blot and qRT-PCR were used to detect indicated molecules.KEY FINDINGS:Endocan effectively decreased TNF-α, IFN-γ, IL-1β, and IL-6 levels as well as relieved pulmonary epithelium cell apoptosis caused by LPS exposure. Endocan significantly reversed LPS induced UPRmt and promoted cell metabolism reprogramming which were crucial for the protective characteristic of endocan in ALI mice model.SIGNIFICANCE:The above findings suggested endocan could significantly suppress inflammatory response in ALI model through attenuating UPRmt associated apoptosis and switch cellular bioenergetics, indicating endocan could be considered as a promising compound against LPS induced ALI.

Baicalin, an important flavonoid in Scutellaria baicalensis Georgi extracts, exerts a variety of pharmacological effects. In this study, we explored the effects of baicalin on chronic hypoxia-induced pulmonary arterial hypertension (PAH) and investigated the mechanism underlying these effects. Moreover, we examined whether the inflammatory response was mediated by the A2A receptor (A2AR) and stromal cell-derived factor-1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR4)-induced phosphatidyl inositol-3-kinase (PI3K) signaling in vivo.

Recent studies have shown that both adenosine monophosphate activated protein kinase (AMPK) and the mammalian target of rapamycin (mTOR) are energy sensors and are related to autophagy. Our recent reports have shown that salidroside can exert protective effects against hypoxia-induced pulmonary arterial smooth muscle cell (PASMC) proliferation and apoptosis resistance through the AMPK pathway. This study aims to explore the relationship among AMPK, mTOR and ULK1 in PASMCs under hypoxic conditions and to investigate whether the protective effects of salidroside are related to the autophagic cell death pathway.