Periplaneta Americana Extract Ameliorates LPS-induced Acute Lung Injury Via Reducing Inflammation and Oxidative Stress

Objective Acute lung injury(ALI)is an acute clinical syndrome characterized by uncontrolled inflammation response,which causes high mortality and poor prognosis.The present study determined the protective effect and underlying mechanism of Periplaneta americana extract(PAE)against lipopolysaccharide(LPS)-induced ALI.Methods The viability of MH-S cells was measured by MTT.ALI was induced in BALB/c mice by intranasal administration of LPS(5 mg/kg),and the pathological changes,oxidative stress,myeloperoxidase activity,lactate dehydrogenase activity,inflammatory cytokine expression,edema formation,and signal pathway activation in lung tissues and bronchoalveolar lavage fluid(BALF)were examined by H&E staining,MDA,SOD and CAT assays,MPO assay,ELISA,wet/dry analysis,immunofluorescence staining and Western blotting,respectively.Results The results revealed that PAE obviously inhibited the release of proinflammatory TNF-α,IL-6 and IL-1βby suppressing the activation of MAPK/Akt/NF-κB signaling pathways in LPS-treated MH-S cells.Furthermore,PAE suppressed the neutrophil infiltration,permeability increase,pathological changes,cellular damage and death,pro-inflammatory cytokines expression,and oxidative stress upregulation,which was associated with its blockage of the MAPK/Akt/NF-κB pathway in lung tissues of ALI mice.Conclusion PAE may serve as a potential agent for ALI treatment due to its anti-inflammatory and anti-oxidative properties,which correlate to the blockage of the MAPK/NF-κB and AKT signaling pathways.

Baicalein ameliorates LPS-induced acute lung injury in mice through Inhibition of inflammatory responses

Aim To study the effects of baicalein （BC）, a phenolic flavonoid extracted mainly from Scutellaria ba- icalensis Georgi, on lipopolysaccharide （LPS）-induced acute lung injury （ALI） in mice and the molecular mecha- nisms underlying. Methods Mice were administrated intranasally with LPS （20 mg · kg^-1/body weight） to estab- lish the ALI model. Then the mice were treated twice with BC （50,100 and 200 mg · kg^-1, p. o. ） 0. 5 hour and 12 hours after LPS stimulation, following another 12 hours, the lungs were collected for histological study. Results LPS caused marked inflammatory cell infiltration and myeloperoxidase activation in lungs, accompanied by significantly in- creased lung W/D ratio, from 7.97±0. 60 in normal group to 12. 49 ± 1.49 in the model. 77.88% reduction in the lung W/D ratio was observed in 200 mg· kg^-1 dose of baicalein. The myeloperoxidase activity was reduced to 40. 14% in mice treated with 200 mg · kg^-1. The number of total cells, neutrophils, and macrophages in BALF de- creased with increasing concentration of baicalein. Inflammatory cytokines level in serum declined significantly while insignificant changes of the same in BALF was observed in mice treated with 50,100 and 200 mg · kg^-1 doses of ba- icalein. Furthermore, LPS induced markedly the expression of inflammasomes and other inflammation-related genes in lung tissue. Treatment of LPS-exposed mice with BC significantly reduced the expression levels of these genes and al- leviated the pathological changes in lungs. Moreover, 1 μmol · L^-1 and 10 μmol · L^-1 BC inhibited remarkably the nuclear translocation of NF-kappaB p65 in Raw264.7 cells. Conclusion Baicalein alleviates LPS-induced acute lung injury in mice by suppressing NF-KB-mediated inflammatory responses and downregulation of inflammasomes.

Effects of methyl palmitate and lutein on LPS-induced acute lung injury in rats

AIM: To investigate the effects of methyl palmitate and lutein on lipopolysaccharide(LPS)-induced acute lung injury(ALI) in rats and explore the possible mechanisms. METHODS: Male Sprague-Dawley rats were divided into 4 groups:(1) control;(2) LPS;(3) Methyl palmitate; and(4) Lutein groups. Methyl palmitate(300 mg/kg, ip) was administered 3 times per week on alternating days while lutein(100 mg/kg, oral) was given once daily. After 1 wk of vehicle/methyl palmitate/lutein treatment, ALI was induced by a single dose of LPS(7.5 mg/kg, iv). After 24 h of LPS injection, animals were sacrificed then biochemical parameters and histopathology were assessed. RESULTS: Treatment with methyl palmitate attenuated ALI, as it significantly decreased the lung wet/dry weight(W/D) ratio, the accumulation of the inflammatory cells in the bronchoalveolar lavage fluid(BALF) andhistopathological damage. However, methyl palmitate failed to decrease lactate dehydrogenase(LDH) activity in BALF. On the other hand, lutein treatment produced significant anti-inflammatory effects as revealed by significant decrease in accumulation of inflammatory cells in lung, LDH level in BALF and histopathological damage. Methyl palmitate and lutein significantly increased superoxide dismutase(SOD) and reduced glutathione(GSH) activities with significant decrease in the lung malondialdehyde(MDA) content. Importantly, methyl palmitate and lutein decreased the level of the inflammatory cytokine tumor necrosis factor-α(TNF-α) in the lung. Lutein also reduced LPS-mediated overproduction of pulmonary nitrite/nitrate(NO-2/NO-3), which was not affected by methyl palmitate pretreatment. CONCLUSION: These results demonstrate the potent protective effects of both methyl palmitate and lutein against LPS-induced ALI in rats. These effects can be attributed to potent antioxidant activities of these agents, which suppress inflammatory cell infiltration and regulated cytokine effects.

DUSP8 inhibits LPS-induced acute lung injury by regulating macrophage response

Background:Although many studies focus on investigating the new therapeutic target of acute lung injury(ALI),there still needs more works on exploring the role of other molecular in the pathology of ALI.Dual specificity phosphatase(DUSP)8 has been reported to participate in the process of tumor.However,the potential role of DUSP8 in lipopolysaccharide(LPS)-induced murine ALI is still unclear.Methods:Firstly,murine ALI was established by LPS treatment and further measured by hematoxylin-eosin staining.Next,the expression of DUSP8 in lung tissues was analyzed by real-time polymerase chain reaction.Then,DUSP8 overexpression vector was utilized and the protein level of DUSP8 was detected by western blot.Moreover,the pathologic injury was measured by hematoxylin-eosin staining and wet/dry ratio.Meanwhile,we cultured bone-marrow-derived macrophages and detected the expression of DUSP8 by real-time polymerase chain reaction and western blot after LPS treatment.In addition,DUSP8 overexpression vector was transfected into bone-marrow-derived macrophages and the levels of related inflammatory cytokines were measured by enzyme-linked immunosorbent assay.Results:Compared with the control mice,DUSP8 significantly decreased in LPS-induced murine ALI.Next,DUSP8 overexpression could attenuate the pathology of ALI by altering lung inflammation and edema.Meanwhile,DUSP8 was also reduced in LPS-treated BMDM and reached a peak at 12h.Besides,DUSP8 overexpression could reduce the productions of related inflammatory cytokines,such as interleukin-1β,tumor necrosis factor-αand interleukin-6 in LPS-treated bone-marrow-derived macrophages.Conclusion:DUSP8 is reduced in LPS-induced murine acute lung injury and DUSP8 overexpression could ameliorate the pathologic injury of ALI by altering macrophage inflammation responses.

Targeting TLR4 and regulating the Keap1/Nrf2 pathway with andrographolide to suppress inflammation and ferroptosis in LPS-induced acute lung injury

Acute lung injury(ALI)is a severe inflammatory condition with a high mortality rate,often precipitated by sepsis.The pathophysiology of ALI involves complex mechanisms,including inflammation,oxidative stress,and ferroptosis,a novel form of regulated cell death.This study explores the therapeutic potential of andrographolide(AG),a bioactive compound derived from Andrographis,in mitigating Lipopolysaccharide(LPS)-induced inflammation and ferroptosis.Our research employed in vitro experiments with RAW264.7 macrophage cells and in vivo studies using a murine model of LPS-induced ALI.The results indicate that AG significantly suppresses the production of pro-inflammatory cytokines and inhibits ferroptosis in LPS-stimulated RAW264.7 cells.In vivo,AG treatment markedly reduces lung edema,decreases inflammatory cell infiltration,and mitigates ferroptosis in lung tissues of LPS-induced ALI mice.These protective effects are mediated via the modulation of the Toll-like receptor 4(TLR4)/Kelch-like ECH-associated protein 1(Keap1)/Nuclear factor erythroid 2-related factor 2(Nrf2)signaling pathway.Molecular docking simulations identified the binding sites of AG on the TLR4 protein(Kd value:-33.5 kcal·mol^(-1)),and these interactions were further corroborated by Cellular Thermal Shift Assay(CETSA)and SPR assays.Collectively,our findings demonstrate that AG exerts potent anti-inflammatory and anti-ferroptosis effects in LPS-induced ALI by targeting TLR4 and modulating the Keap1/Nrf2 pathway.This study underscores AG's potential as a therapeutic agent for ALI and provides new insights into its underlying mechanisms of action.

Association of interleukin-6 with acute lung injury risk and disease severity in sepsis

Sepsis is a life-threatening condition caused by a dysregulated response of the body in response to an infection that harms its tissues and organs.Interleukin-6(IL-6)is a significant component of the inflammatory response as part of the pa-thogenesis of sepsis.It aids in the development of Acute lung injury and,subse-quently,multiple organ dysfunction syndrome.This letter probes into the corre-lation between plasma IL-6 levels and the risk of developing acute lung injury and multiple organ dysfunction syndrome in critically ill patients with sepsis.While it shows promising results,limitations like its observational study design,a limited sample size,a single center involvement,single-time-point measurement,and a lack of a control group restrain its cogency.The study is a big step in identifying IL-6 as a biomarker to improve patient care.

Tectorigenin inhibits the inflammation of LPS-induced acute lung injury in mice

AIM: In a previous study, the anti-inflammatory effects of tectorigenin were disclosed. In this study, the anti-inflammatory effects of tectorigenin on acute lung injury using a lipopolysaccharide(LPS)-induced acute lung injury(ALI) mouse model were investigated. METHOD: The cell-count in the bronchoalveolar lavage fluid(BALF) was measured. The animal lung edema degree was evaluated by the wet/dry weight(W/D) ratio. The superoxidase dismutase(SOD) activity and myeloperoxidase(MPO) activity was assayed using SOD and MPO kits, respectively. The levels of inflammatory mediators, including tumor necrosis factor-α(TNF-α), IL-1β, and IL-6 were assayed using an enzyme-linked immunosorbent assay method. Pathological changes of lung tissues were observed through HE staining. The inflammatory signal pathway related protein nuclear factor NF-κB p65 mR NA expression was measured by real-time PCR, and the protein level of NF-κB p65 was measured using Western blotting analysis. RESULTS: The data showed that treatment with the tectorigenin markedly attenuated the inflammatory cell numbers in the BALF, decreased nuclear factor NF-κB p65 mR NA level and protein level in the lungs, and improved SOD activity and inhibited MPO activity. Histological studies showed that tectorigenin substantially inhibited LPS-induced neutrophils in lung tissue compared with the model group. CONCLUSION: The results indicated that tectorigenin had a protective effect on LPS-induced ALI in mice.

Sangxingtang inhibits the inflammation of LPS-induced acute lung injury in mice by down-regulating the MAPK/NF-κB pathway

In the present study, we investigated anti-inflammatory effects of Sangxingtang(SXT) on acute lung injury using a lipopolysaccharide(LPS)-induced acute lung injury(ALI) mouse model. The cell counting in the bronchoalveolar lavage fluid(BALF) was performed. The degree of lung edema was evaluated by measuring the wet/dry weight(W/D) ratio. The superoxidase dismutase(SOD) and myeloperoxidase(MPO) activities were assayed by SOD and MPO kits, respectively. The levels of inflammatory mediators, including tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6), were assayed by the enzyme-linked immunosorbent assay methods. Pathological changes of lung tissues were observed by Hematoxylin and eosin(HE) staining. The inflammatory signaling pathway-related proteins nuclear factor mitogen activated protein kinases(P38MAPK), extracellular regulated protein kinases(Erk), c-Jun N-terminal kinase(Jnk) and nuclear transcription factor(NF-κB) p65 expressions were measured by Western blotting. Our results showed that the treatment with the SXT markedly attenuated the inflammatory cell numbers in the BALF, decreased the levels of P-P38 MAPK, P-Erk, P-Jnk and P-NF-κB p65 and the total protein levels in lungs, improved the SOD activity and inhibited the MPO activity. Histological studies demonstrated that SXT substantially reduced the LPS-induced neutrophils in lung tissues, compared with the untreated LPS group. In conclusion, our results indicated that SXT had protective effects on LPS-induced ALI in mice.

Xuebijing alleviates LPS-induced acute lung injury by downregulating pro-inflammatory cytokine production and inhibiting gasdermin-E-mediated pyroptosis of alveolar epithelial cells

Acute lung injury/acute respiratory distress syndrome(ALI/ARDS)is characterized by diffuse alveolar injury primarily caused by an excessive inflammatory response.Regrettably,the lack of effective pharmacotherapy currently available contributes to the high mortality rate in patients with this condition.Xuebijing(XBJ),a traditional Chinese medicine recognized for its potent anti-inflammatory properties,exhibits promise as a potential therapeutic agent for ALI/ARDS.This study aimed to explore the preventive effects of XBJ on ALI and its underlying mechanism.To this end,we established an LPS-induced ALI model and treated ALI mice with XBJ.Our results demonstrated that pre-treatment with XBJ significantly alleviated lung inflammation and increased the survival rate of ALI mice by 37.5%.Moreover,XBJ substantially suppressed the production of TNF-α,IL-6,and IL-1βin the lung tissue.Subsequently,we performed a network pharmacology analysis and identified identified 109 potential target genes of XBJ that were mainly involved in multiple signaling pathways related to programmed cell death and anti-inflammatory responses.Furthermore,we found that XBJ exerted its inhibitory effect on gasdermin-E-mediated pyroptosis of lung cells by suppressing TNF-αproduction.Therefore,this study not only establishes the preventive efficacy of XBJ in ALI but also reveals its role in protecting alveolar epithelial cells against gasdermin-E-mediated pyroptosis by reducing TNF-αrelease.

Synthesis and evaluation of 2-cyano-3, 12-dioxooleana-1, 9(11)-en-28-oate-13β, 28-olide as a potent anti-inflammatory agent for intervention of LPS-induced acute lung injury

The present study was designed to synthesize 2-Cyano-3, 12-dioxooleana-1, 9(11)-en-28-oate-13β, 28-olide(1), a lactone derivative of oleanolic acid(OA) and evaluate its anti-inflammatory activity. Compound 1 significantly diminished nitric oxide(NO) production and down-regulated the m RNA expression of iNOS, COX-2, IL-6, IL-1β, and TNF-α in lipopolysaccharide(LPS)-stimulated RAW264.7 cells. Further in vivo studies in murine model of LPS-induced acute lung injury(ALI) showed that 1 possessed more potent protective effects than the well-known anti-inflammatory drug dexamethasone by inhibiting myeloperoxidase(MPO) activity, reducing total cells and neutrophils, and suppressing inflammatory cytokines expression, and thus ameliorating the histopathological conditions of the injured lung tissue. In conclusion, compound 1 could be developed as a promising anti-inflammatory agent for intervention of LPS-induced ALI.

Jinyinqingre Oral Liquid alleviates LPS-induced acute lung injury by inhibiting the NF-κB/NLRP3/GSDMD pathway

Acute lung injury(ALI)is a prevalent and severe clinical condition characterized by inflammatory damage to the lung endothelial and epithelial barriers,resulting in high incidence and mortality rates.Currently,there is a lack of safe and effective drugs for the treatment of ALI.In a previous clinical study,we observed that Jinyinqingre oral liquid(JYQR),a Traditional Chinese Medicine formulation prepared by the Taihe Hospital,Affiliated Hospital of Hubei University of Medicine,exhibited notable efficacy in treating inflammation-related hepatitis and cholecystitis in clinical settings.However,the potential role of JYQR in ALI/acute respiratory distress syndrome(ARDS)and its anti-inflammatory mechanism remains unexplored.Thus,the present study aimed to investigate the therapeutic effects and underlying molecular mechanisms of JYQR in ALI using a mouse model of lipopolysaccharide(LPS)-induced ALI and an in vitro RAW264.7 cell model.JYQR yielded substantial improvements in LPS-induced histological alterations in lung tissues.Additionally,JYQR administration led to a noteworthy reduction in total protein levels within the BALF,a decrease in MPAP,and attenuation of pleural thickness.These findings collectively highlight the remarkable efficacy of JYQR in mitigating the deleterious effects of LPS-induced ALI.Mechanistic investigations revealed that JYQR pretreatment significantly inhibited NF-κB activation and downregulated the expressions of the downstream proteins,namely NLRP3 and GSDMD,as well as proinflammatory cytokine levels in mice and RAW2647 cells.Consequently,JYQR alleviated LPS-induced ALI by inhibiting the NF-κB/NLRP3/GSDMD pathway.JYQR exerts a protective effect against LPS-induced ALI in mice,and its mechanism of action involves the downregulation of the NF-κB/NLRP3/GSDMD inflammatory pathway.

Impact of interleukin 6 levels on acute lung injury risk and disease severity in critically ill sepsis patients

BACKGROUND Sepsis is a life-threatening condition characterized by a dysregulation of the host response to infection that can lead to acute lung injury(ALI)and multiple organ dysfunction syndrome(MODS).Interleukin 6(IL-6)is a pro-inflammatory cytokine that plays a crucial role in the pathogenesis of sepsis and its complications.AIM To investigate the relationship among plasma IL-6 levels,risk of ALI,and disease severity in critically ill patients with sepsis.METHODS This prospective and observational study was conducted in the intensive care unit of a tertiary care hospital between January 2021 and December 2022.A total of 83 septic patients were enrolled.Plasma IL-6 levels were measured upon admission using an enzyme-linked immunosorbent assay.The development of ALI and MODS was monitored during hospitalization.Disease severity was evaluated by Acute Physiology and Chronic Health Evaluation II(APACHE II)and Sequential Organ Failure Assessment(SOFA)scores.RESULTS Among the 83 patients with sepsis,38(45.8%)developed ALI and 29(34.9%)developed MODS.Plasma IL-6 levels were significantly higher in patients who developed ALI than in those without ALI(median:125.6 pg/mL vs 48.3 pg/mL;P<0.001).Similarly,patients with MODS had higher IL-6 levels than those without MODS(median:142.9 pg/mL vs 58.7 pg/mL;P<0.001).Plasma IL-6 levels were strongly and positively correlated with APACHE II(r=0.72;P<0.001)and SOFA scores(r=0.68;P<0.001).CONCLUSIONElevated plasma IL-6 levels in critically ill patients with sepsis were associated with an increased risk of ALI andMODS.Higher IL-6 levels were correlated with greater disease severity,as reflected by higher APACHE II andSOFA scores.These findings suggest that IL-6 may serve as a biomarker for predicting the development of ALI anddisease severity in patients with sepsis.

MicroRNA-451 from Human Umbilical Cord-Derived Mesenchymal Stem Cell Exosomes Inhibits Alveolar Macrophage Autophagy via Tuberous Sclerosis Complex 1/Mammalian Target of Rapamycin Pathway to Attenuate Burn-Induced Acute Lung Injury in Rats

Objective Our previous studies established that microRNA(miR)-451 from human umbilical cord mesenchymal stem cell-derived exosomes(hUC-MSC-Exos)alleviates acute lung injury(ALI).This study aims to elucidate the mechanisms by which miR-451 in hUC-MSC-Exos reduces ALI by modulating macrophage autophagy.Methods Exosomes were isolated from hUC-MSCs.Severe burn-induced ALI rat models were treated with hUC-MSC-Exos carrying the miR-451 inhibitor.Hematoxylin-eosin staining evaluated inflammatory injury.Enzyme-linked immunosorbnent assay measured lipopolysaccharide(LPS),tumor necrosis factor-α,and interleukin-1βlevels.qRT-PCR detected miR-451 and tuberous sclerosis complex 1(TSC1)expressions.The regulatory role of miR-451 on TSC1 was determined using a dual-luciferase reporter system.Western blotting determined TSC1 and proteins related to the mammalian target of rapamycin(mTOR)pathway and autophagy.Immunofluorescence analysis was conducted to examine exosomes phagocytosis in alveolar macrophages and autophagy level.Results hUC-MSC-Exos with miR-451 inhibitor reduced burn-induced ALI and promoted macrophage autophagy.MiR-451 could be transferred from hUC-MSCs to alveolar macrophages via exosomes and directly targeted TSC1.Inhibiting miR-451 in hUC-MSC-Exos elevated TSC1 expression and inactivated the mTOR pathway in alveolar macrophages.Silencing TSC1 activated mTOR signaling and inhibited autophagy,while TSC1 knockdown reversed the autophagy from the miR-451 inhibitor-induced.Conclusion miR-451 from hUC-MSC exosomes improves ALI by suppressing alveolar macrophage autophagy through modulation of the TSC1/mTOR pathway,providing a potential therapeutic strategy for ALI.

Mogroside IIE,an in vivo metabolite of sweet agent,alleviates acute lung injury via Pla2g2a-EGFR inhibition

In the face of increasingly serious environmental pollution,the health of human lung tissues is also facing serious threats.Mogroside IIE(M2E)is the main metabolite of sweetening agents mogrosides from the anti-tussive Chinese herbal Siraitia grosvenori.The study elucidated the anti-inflammatory action and molecular mechanism of M2E against acute lung injury(ALI).A lipopolysaccharide(LPS)-induced ALI model was established in mice and MH-S cells were employed to explore the protective mechanism of M2E through the western blotting,co-immunoprecipitation,and quantitative real time-PCR analysis.The results indicated that M2E alleviated LPS-induced lung injury through restraining the activation of secreted phospholipase A2 type IIA(Pla2g2a)-epidermal growth factor receptor(EGFR).The interaction of Pla2g2a and EGFR was identified by co-immunoprecipitation.In addition,M2E protected ALI induced with LPS against inflammatory and damage which were significantly dependent upon the downregulation of AKT and m TOR via the inhibition of Pla2g2a-EGFR.Pla2g2a may represent a potential target for M2E in the improvement of LPS-induced lung injury,which may represent a promising strategy to treat ALI.

Mechanisms and Research Progress of Traditional Chinese Medicine Regulating NF-κB in the Treatment of Acute Lung Injury/Acute Respiratory Distress Syndrome

Acute lung injury(ALI)has multiple causes and can easily progress to acute respiratory distress syndrome(ARDS)if not properly treated.Nuclear factorκB(NF-κB)is a key pathway in the treatment of ALI/ARDS.By exploring the relevance of NF-κB and the pathogenesis of this disease,it was found that this disease was mainly associated with inflammation,dysfunction of the endothelial barrier,oxidative stress,impaired clearance of alveolar fluid,and coagulation disorders.Traditional Chinese medicine(TCM)has the characteristics of multitargeting,multipathway effects,and high safety,which can directly or indirectly affect the treatment of ALI/ARDS.This article summarizes the mechanism and treatment strategies of TCM in recent years through intervention in the NF-κB-related signaling pathways for treating ALI/ARDS.It provides an overview from the perspectives of Chinese herbal monomers,TCM couplet medicines,TCM injections,Chinese herbal compounds,and Chinese herbal preparations,offering insights into the prevention and treatment of ALI/ARDS with TCM.

Research Progress on the Pathogenesis of Acute Lung Injury(ALI)

In this review,the databases searched were PubMed and Web of Science.It is believed that the main causes of acute lung injury(ALI)and acute respiratory distress syndrome(ARDS)are inflammatory response disorders,excessive oxidative stress,cell death,endoplasmic reticulum stress,coagulation dysfunction,and weakened aquaporin function.

Modulating the crosstalk between macrophage and Th17: potential mechanism of natural products on acute lung injury

Sepsis is a life-threatening multiple organ dysfunction syndrome caused by the imbalance of the immune response to infection,featuring complex and variable conditions,and is one of the leading causes of mortality in ICU patients.Lung injury is a common organ damage observed in sepsis patients.Macrophages and Th17 cells,as crucial components of innate and adaptive immunity,play pivotal roles in the development of sepsis-induced acute lung injury(ALI).This review summarizes the alterations and mechanisms of macrophages and Th17 cells in sepsis-induced ALI.By focusing on the“cross-talk”between macrophages and Th17 cells,this review aims to provide a solid theoretical foundation for further exploring the therapeutic targets of traditional Chinese medicine formulas in the treatment of sepsis complicated with ALI,thereby offering insights and guidance for the clinical application of traditional Chinese medicine in managing sepsis-associated ALI.

Acute lung injury and ARDS in acute pancreatitis: Mechanisms and potential intervention

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in acute pancreatitis still represents a substantial problem,with a mortality rate in the range of 30%-40%.The present review evaluates underlying pathophysiological mechanisms in both ALI and ARDS and potential clinical implications.Several mediators and pathophysiological pathways are involved during the different phases of ALI and ARDS.The initial exudative phase is characterized by diffuse alveolar damage,microvascular injury and influx of inflammatory cells.This phase is followed by a fibro-proliferative phase with lung repair,type Ⅱ pneumocyte hypoplasia and proliferation of fibroblasts.Proteases derived from polymorphonuclear neutrophils,various pro-inflammatory mediators,and phospholipases are all involved,among others.Contributing factors that promote pancreatitis-associated ALI may be found in the gut and mesenteric lymphatics.There is a lack of complete understanding of the underlying mechanisms,and by improving our knowledge,novel tools for prevention and intervention may be developed,thus contributing to improved outcome.

Dexmedetomidine Alleviates Pulmonary Edema by Upregulating AQP1 and AQP5 Expression in Rats with Acute Lung Injury Induced by Lipopolysaccharide

This study aims to elucidate the mechanisms by which dexmedetomidine alleviates pulmonary edema in rats with acute lung injury induced by lipopolysaccharide （LPS）. Male Wistar rats were randomly divided into five groups： normal saline control （NS） group, receiving intravenous 0.9% normal saline （5 mL/kg）; LPS group, receiving intravenous LPS （10 mg/kg）; small-dose dexmedetomidine （S） group, treated with a small dose of dexmedetomidine （0.5 μg·kg^-1·h^-1）; medium-dose dexmedetomidine （M） group, treated with a medium dose of dexmedetomidine （2.5 μg·kg^-1·h^-1）; high-dose dexmedetomidine （H） group, treated with a high dose of dexmedetomidine （5μg·kg^-1·h^-1）. The rats were sacrificed 6 h after intravenous injection of LPS or NS, and the hmgs were removed for evaluating histological characteristics and determining the lung wet/dry weight ratio （W/D）. The levels of tumor necrosis factor-alpha （TNF-α） and interleukin-1β （IL-1β） in the lung tissues were assessed by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expression levels of aquaporin-1 （AQP1） and aquaporin-5 （AQP5） were detected by RT-PCR, immunohistochemistry, and Western blot- ting. The lung tissues from the LPS groups were significantly damaged, which were less pronounced in the H group but not in the small-dose dexmedetomidine group or medium-dose dexmedetomidine group. The W/D and the concentrations of TNF-α and IL-1β in the pulmonary tissues were increased in the LPS group as compared with those in NS group, which were reduced in the H group but not in S group or M group （P〈0.01）. The expression of AQP1 and AQP5 was lower in the LPS group than in the NS group, and significantly increased in the H group but not in the S group or M group （P〈0.01）. Our findings suggest that dexmedetomidine may alleviate pulmonary edema by increasing the expression of AQP-1 and AQP-5.

Circulating miRNAs as biomarkers for severe acute pancreatitis associated with acute lung injury

AIM To identify circulating micro(mi)RNAs as biological markers for prediction of severe acute pancreatitis(SAP) with acute lung injury(ALI).METHODS Twenty-four serum samples were respectively collected and classified as SAP associated with ALI and SAP without ALI, and the mi RNA expression profiles were determined by microarray analysis. These mi RNAs were validated by quantitative reverse transcriptionpolymerase chain reaction, and their putative targets were predicted by the online software Target Scan, mi Randa and Pic Tar database. Gene ontology(GO) and Kyoto encyclopedia of genes and genomes(commonly known as KEGG) were used to predict their possible functions and pathways involved.RESULTS We investigated 287 mi RNAs based on microarray data analysis. Twelve mi RNAs were differentially expressed in the patients with SAP with ALI and those with SAP without ALI. Hsa-mi R-1260 b, 762, 22-3 p, 23 b and 23 a were differently up-regulated and hsa-mi R-550 a*, 324-5 p, 484, 331-3 p, 140-3 p, 342-3 p and 150 were differently down-regulated in patients with SAP with ALI compared to those with SAP without ALI. In addition, 85 putative target genes of the significantly dysregulated mi RNAs were found by Target Scan, mi Randa and Pic Tar. Finally, GO and pathway network analysis showed that they were mainly enriched in signal transduction, metabolic processes, cytoplasm and cell membranes.CONCLUSION This is the first study to identify 12 circulating mi RNAs in patients with SAP with ALI, which may be biomarkers for prediction of ALI after SAP.