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.

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.

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.

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.

The Role of Oxygen Radicals in Rat Acute Lung Injury Induced by Phorbol Myristate Acetate

We tried to clarify the role of oxygen radicals released from granulocytes stimulated byphorbol myristate acetate(PMA) in rat acute lung injury. It was found that DNA strand-breakdamage(DSBD) in peripheral white blood cells (WBC) was significantly increased 40 min after injec-tion of PMA. DSBD in lung tissue of rats treated with PMA was also markedly increased comparedwith the controls. The PMA-treated rats showed significantly higher lipid-peroxide (LPO) level inplasma and lung tissue hemogenate than the controls did. These results suggest that determination ofDSBD, a simple and sensitive indicator for oxygen radical damaging, might be useful in thediagnosis of adult respiratory distress syndrome (ARDS), when it is used together with themeasurement of plasma LPO.

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.

Network pharmacology and molecular docking to explore Polygoni Cuspidati Rhizoma et Radix treatment for acute lung injury

BACKGROUND Polygoni Cuspidati Rhizoma et Radix(PCRR),a well-known traditional Chinese medicine(TCM),inhibits inflammation associated with various human diseases.However,the anti-inflammatory effects of PCRR in acute lung injury(ALI)and the underlying mechanisms of action remain unclear.AIM To determine the ingredients related to PCRR for treatment of ALI using multiple databases to obtain potential targets for fishing.METHODS Recognized and candidate active compounds for PCRR were obtained from Traditional Chinese Medicine Systems Pharmacology,STITCH,and PubMed databases.Target ALI databases were built using the Therapeutic Target,DrugBank,DisGeNET,Online Mendelian Inheritance in Man,and Genetic Association databases.Network pharmacology includes network construction,target prediction,topological feature analysis,and enrichment analysis.Bioinformatics resources from the Database for Annotation,Visualization and Integrated Discovery were utilized for gene ontology biological process and Kyoto Encyclopedia of Genes and Genomes network pathway enrichment analysis,and molecular docking techniques were adopted to verify the combination of major active ingredients and core targets.RESULTS Thirteen bioactive compounds corresponding to the 433 PCRR targets were identified.In addition,128 genes were closely associated with ALI,60 of which overlapped with PCRR targets and were considered therapeutically relevant.Functional enrichment analysis suggested that PCRR exerted its pharmacological effects in ALI by modulating multiple pathways,including the cell cycle,cell apoptosis,drug metabolism,inflammation,and immune modulation.Molecular docking results revealed a strong associative relationship between the active ingredient and core target.CONCLUSION PCRR alleviates ALI symptoms via molecular mechanisms predicted by network pharmacology.This study proposes a strategy to elucidate the mechanisms of TCM at the network pharmacology level.

Veno-Venous Extracorporeal Membrane Oxygenation for Acute Lung Injury after Surgery for Aortic Dissection: A Case Report

Acute respiratory failure after surgery for aortic dissection is a serious complication that has been associated with increased mortality and morbidity. Veno-venous (VV) extracorporeal membrane oxygenation (ECMO) is reported as one of the treatments for this life-threatening complication. A 78-year-old male patient was admitted to our hospital for Stanford type A acute aortic dissection. He underwent emergency replacement of the ascending aorta, after which he developed acute lung injury. It was difficult to maintain oxygenation with a respirator mask. Therefore, VV-ECMO was initiated on postoperative day 1. The oxygenation gradually improved, and VV-ECMO was continued until postoperative day 13. On postoperative day 25, mechanical ventilation was withdrawn. The patient was discharged from the hospital on postoperative day 149. We report a case of successful treatment of acute lung injury with VV-ECMO initiated after surgery for aortic dissection. VV-ECMO can be considered as a treatment option for severe acute lung injury after surgery for aortic dissection.

Multiomics reveal human umbilical cord mesenchymal stem cells improving acute lung injury via the lung-gut axis

BACKGROUND Acute lung injury(ALI)and its final severe stage,acute respiratory distress syndrome,are associated with high morbidity and mortality rates in patients due to the lack of effective specific treatments.Gut microbiota homeostasis,including that in ALI,is important for human health.Evidence suggests that the gut microbiota improves lung injury through the lung-gut axis.Human umbilical cord mesenchymal cells(HUC-MSCs)have attractive prospects for ALI treatment.This study hypothesized that HUC-MSCs improve ALI via the lung-gut microflora.AIM To explore the effects of HUC-MSCs on lipopolysaccharide(LPS)-induced ALI in mice and the involvement of the lung-gut axis in this process.METHODS C57BL/6 mice were randomly divided into four groups(18 rats per group):Sham,sham+HUC-MSCs,LPS,and LPS+HUC-MSCs.ALI was induced in mice by intraperitoneal injections of LPS(10 mg/kg).After 6 h,mice were intervened with 0.5 mL phosphate buffered saline(PBS)containing 1×10^(6) HUC-MSCs by intraperitoneal injections.For the negative control,100 mL 0.9%NaCl and 0.5 mL PBS were used.Bronchoalveolar lavage fluid(BALF)was obtained from anesthetized mice,and their blood,lungs,ileum,and feces were obtained by an aseptic technique following CO_(2) euthanasia.Wright’s staining,enzyme-linked immunosorbent assay,hematoxylin-eosin staining,Evans blue dye leakage assay,immunohistochemistry,fluorescence in situ hybridization,western blot,16S rDNA sequencing,and non-targeted metabolomics were used to observe the effect of HUC-MSCs on ALI mice,and the involvement of the lung-gut axis in this process was explored.One-way analysis of variance with post-hoc Tukey’s test,independent-sample Student’s t-test,Wilcoxon rank-sum test,and Pearson correlation analysis were used for statistical analyses.RESULTS HUC-MSCs were observed to improve pulmonary edema and lung and ileal injury,and decrease mononuclear cell and neutrophil counts,protein concentrations in BALF and inflammatory cytokine levels in the serum,lung,and ileum of ALI mice.Especially,HUC-MSCs decreased Evans blue concentration and Toll-like receptor 4,myeloid differentiation factor 88,p-nuclear factor kappa-B(NF-κB)/NF-κB,and p-inhibitorαof NF-κB(p-IκBα)/IκBαexpression levels in the lung,and raised the pulmonary vascular endothelial-cadherin,zonula occludens-1(ZO-1),and occludin levels and ileal ZO-1,claudin-1,and occludin expression levels.HUC-MSCs improved gut and BALF microbial homeostases.The number of pathogenic bacteria decreased in the BALF of ALI mice treated with HUCMSCs.Concurrently,the abundances of Oscillospira and Coprococcus in the feces of HUS-MSC-treated ALI mice were significantly increased.In addition,Lactobacillus,Bacteroides,and unidentified_Rikenellaceae genera appeared in both feces and BALF.Moreover,this study performed metabolomic analysis on the lung tissue and identified five upregulated metabolites and 11 downregulated metabolites in the LPS+MSC group compared to the LPS group,which were related to the purine metabolism and the taste transduction signaling pathways.Therefore,an intrinsic link between lung metabolite levels and BALF flora homeostasis was established.CONCLUSION This study suggests that HUM-MSCs attenuate ALI by redefining the gut and lung microbiota.

Preemptive mechanical ventilation can block progressive acute lung injury

Mortality from acute respiratory distress syndrome(ARDS) remains unacceptable, approaching 45% in certain high-risk patient populations. Treating fulminant ARDS is currently relegated to supportive care measures only. Thus, the best treatment for ARDS may lie with preventing this syndrome from ever occurring. Clinical studies were examined to determine why ARDS has remained resistant to treatment over the past several decades. In addition, both basic science and clinical studies were examined to determine the impact that early, protective mechanical ventilation may have on preventing the development of ARDS in at-risk patients. Fulminant ARDS is highly resistant to both pharmacologic treatment and methods of mechanical ventilation. However, ARDS is a progressive disease with an early treatment window that can be exploited. In particular, protective mechanical ventilation initiated before the onset of lung injury can prevent the progression to ARDS. Airway pressure release ventilation(APRV) is a novel mechanical ventilation strategy for delivering a protective breath that has been shown to block progressive acute lung injury(ALI) and prevent ALI from progressing to ARDS. ARDS mortality currently remains as high as 45% in some studies. As ARDS is a progressive disease, the key to treatment lies with preventing the disease from ever occurring while it remains subclinical. Early protective mechanical ventilation with APRV appears to offer substantial benefit in this regard and may be the prophylactic treatment of choice for preventing ARDS.

Ubiquitin Reduces Expression of Intercellular Adhesion Molecules and Tumor Necrosis Factor-α in Lung Tissue of Experimental Acute Lung Injury

Background Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are two important cytokines in inflammatory response, which may induce rolling and adhesion of both leukocytes and lymphocytes, while modulating vascular permeability at the same time. These adhesion molecules usually serve as surrogate markers of activation and injury of vascular endothelial cells. Tumor necrosis factor-α (TNF-α) is a key factor to induce the expression and production of the above cell adhesion molecules. However, it remains to be elucidated whether exogenous ubiquitin exerts any effect on the cytokines in sepsis-induced ALI. Methods Sixty mice were devided randomly into five groups with twelve mice in each group, i.e. CLP group, SHAM group, UB1 group (10 mg/kg), UB2 group (5 mg/kg) and UB3 group(1 mg/kg). Mice of SHAM group underwent sham operation, and other four groups underwent CLP. Six hours after surgery, mice of three UB groups received ubiquitin by caudal vein injection while CLP and SHAM group received vehicle. Seven hours after surgery, blood and lungs of all mice were collected. ICAM-1, VCAM-1 and TNF-α level of 9% lung homogenate and serum TNF-α level were measured by ELISA. Results Pulmonary ICAM-1, VCAM-1 and TNF-α level of three UB groups were lower than CLP and SHAM group, and there were several comparisons with a statistically significant difference. Serum TNF-α level of three UB groups were slightly lower than CLP group, but far higher than SHAM group. Pulmonary ICAM-1 level, VCAM-1 level and serum TNF-α level of UB3 group were lower than UB1 and UB2 group, and there was a significant difference in VCAM-1 between UB3 and UB1 group. Pulmonary TNF-α level of UB3 group was slightly higher than UB1 and UB2 group.

Ulinastatin for acute lung injury and acute respiratory distress syndrome: A systematic review and meta-analysis

AIM: To investigate the efficacy and safety of ulinastatin for patients with acute lung injury(ALI) and those with acute respiratory distress syndrome(ARDS).METHODS: A systematic review of randomized controlled trials(RCTs) of ulinastatin for ALI/ARDS was conducted. Oxygenation index, mortality rate [intensive care unit(ICU) mortality rate, 28-d mortality rate] and length of ICU stay were compared between ulinastatin group and conventional therapy group. Meta-analysis was performed by using Rev Man 5.1.RESULTS: Twenty-nine RCTs with 1726 participants were totally included, the basic conditions of which were similar. No studies discussed adverse effect. Oxygenation index was reported in twenty-six studies(1552 patients). Ulinastatin had a significant effect in improving oxygenation [standard mean difference(SMD) = 1.85, 95%CI: 1.42-2.29, P < 0.00001, I2 = 92%]. ICUmortality and 28-d mortality were respectively reported in eighteen studies(987 patients) and three studies(196 patients). We found that ulinastatin significantly decreased the ICU mortality [I2 = 0%, RR = 0.48, 95%CI: 0.38-0.59, number needed to treat(NNT) = 5.06, P < 0.00001], while the 28-d mortality was not significantly affected(I2 = 0%, RR = 0.78, 95%CI: 0.51-1.19, NNT = 12.66, P = 0.24). The length of ICU stay(six studies, 364 patients) in the ulinastatin group was significantly lower than that in the control group(SMD =-0.97, 95%CI:-1.20--0.75, P < 0.00001, I2 = 86%). CONCLUSION: Ulinastatin seems to be effective for ALI and ARDS though most trials included were of poor quality and no information on safety was provided.

Glycolysis and acute lung injury:A review

Acute lung injury is featured as diffuse pulmonary edema and persistent hypoxemia caused by lung or systemic injury.It is believed that these pathological changes are associated with damage to the alveolar epithelium and vascular endothelium,recruitment of inflammatory cells,and inflammatory factor storms.In recent years,the metabolic reprogramming of lung parenchymal cells and immune cells,particularly alterations in glycolysis,has been found to occur in acute lung injury.Inhibition of glycolysis can reduce the severity of acute lung injury.Thus,this review focuses on the interconnection between acute lung injury and glycolysis and the mechanisms of interaction,which may bring hope for the treatment of acute lung injury.

Extracellular vesicles in the pathogenesis and treatment of acute lung injury

Acute lung injury(ALI)and acute respiratory distress syndrome(ARDS)are common life-threatening lung diseases associated with acute and severe inflammation.Both have high mortality rates,and despite decades of research on clinical ALI/ARDS,there are no effective therapeutic strategies.Disruption of alveolar-capillary barrier integrity or activation of inflammatory responses leads to lung inflammation and injury.Recently,studies on the role of extracellular vesicles(EVs)in regulating normal and pathophysiologic cell activities,including inflammation and injury responses,have attracted attention.Injured and dysfunctional cells often secrete EVs into serum or bronchoalveolar lavage fluid with altered cargoes,which can be used to diagnose and predict the development of ALI/ARDS.EVs secreted by mesenchymal stem cells can also attenuate inflammatory reactions associated with cell dysfunction and injury to preserve or restore cell function,and thereby promote cell proliferation and tissue regeneration.This review focuses on the roles of EVs in the pathogenesis of pulmonary inflammation,particularly ALI/ARDS.

Effects of n-butanol extract of Rumex gmelini Turcz on the endotoxin-induced acute lung injury in mice

Objective: To study the effects of n-butanol extract of Rumex gmelini Turcz on the endotoxin-induced acute lung injury (ALI) in mice. Methods: Kunming mice were selected as experimental animals and randomly divided into normal control group (NC group), acute lung injury group (ALI group) and n-butanol extract of Rumex gmelini Turcz group (Rum group). ALI group and Rum group were established into ALI models by intraperitoneal injection of endotoxin, and Rum group were given intragastric administration of n-butanol extract of Rumex gmelini Turcz for intervention before model establishment. 12 h after endotoxin injection, the superior lobe of right lung was taken to determine the water content, and the inferior lobe of right lung was taken to determine the contents of AQPs molecules, inflammatory response molecules and oxidative stress molecules. Results: 12 h after endotoxin injection, the water content of lung tissue in Rum group was (6.82±0.97)%. After variance analysis, the water content of lung tissue in ALI group was significantly higher than that in NC group, AQP1 and AQP5 protein levels in lung tissue were significantly lower than those of NC group, AQP3 and AQP4 protein levels were not different from those of NC group, and MPO, NF-kB, TNF-α, HMGB1, IL-8, ROS, ATP, MDA, Bax and Caspase-3 protein levels were significantly higher than those of NC group;the water content of lung tissue in Rum group was significantly lower than that in ALI group, AQP1 and AQP5 protein levels in lung tissue were significantly higher than those of ALI group, AQP3 and AQP4 protein levels were not different from those of ALI group, and MPO, NF-kB, TNF-α, HMGB1, IL-8, ROS, ATP, MDA, Bax and Caspase-3 protein levels were significantly lower than those of ALI group. Conclusion:The n-butanol extract of Rumex gmelini Turcz reduce the pulmonary edema, inflammatory response, oxidative stress and apoptosis during the endotoxin-induced ALI in mice.

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.

Intervening Effect of Sodium Aescinate on Pulmonary Fibrosis in Rats with Acute Lung Injury

[Objectives] The aim was to investigate the intervening effect of sodium aescinate on pulmonary fibrosis in rats with acute lung injury( ALI). [Methods] The rats were randomly divided into normal group,model group and sodium aescinate group. The rat model of ALI was induced by administration of oleic acid. The rats in the sodium aescinate group were intravenously injected with sodium aescinate according to the amount of 4 mg/kg for 14 consecutive d. Then,11 rats were selected randomly from each group and slaughtered on Day 1 and Day 14,respectively after last administration. The body mass index,arterial partial pressure of oxygen( PaO_2),oxygenation index( PaO_2/FiO_2),lung index,wet/dry mass ratio of lung,serum IL-1β,TNF-α,PC Ⅲ and TGF-β1 levels of the rats were analyzed. [Results]No significant differences were found in body mass index,lung index or lung wet/dry mass ratio among different groups. Compared with the model group,the PaO_2 and PaO_2/FiO_2 ratio increased significantly( P < 0. 05),the serum IL-1β,TNF-α,PC Ⅲ and TGF-β1 levels declined significantly( P <0. 05),the lung histopathological damage was reduced,and the semi-quantitative histological score( IQA) of damaged lung tissue decreased significantly( P < 0. 01). [Conclusions]Sodium aescinate can reduce the levels of inflammatory factors in rats with ALI,with certain intervening on pulmonary effect.

Acute kidney injury spectrum in patients with chronic liver disease:Where do we stand?

Acute kidney injury (AKI) is a common complication of liver cirrhosis and is of the utmost clinical and prognostic relevance. Patients with cirrhosis, especially decompensated cirrhosis, are more prone to develop AKI than those without cirrhosis. The hepatorenal syndrome type of AKI (HRS–AKI), a spectrum of disorders in prerenal chronic liver disease, and acute tubular necrosis (ATN) are the two most common causes of AKI in patients with chronic liver disease and cirrhosis. Differentiating these conditions is essential due to the differences in treatment. Prerenal AKI, a more benign disorder, responds well to plasma volume expansion, while ATN requires more specific renal support and is associated with substantial mortality. HRS–AKI is a facet of these two conditions, which are characterized by a dysregulation of the immune response. Recently, there has been progress in better defining this clinical entity, and studies have begun to address optimal care. The present review synopsizes the current diagnostic criteria, pathophysiology, and treatment modalities of HRS–AKI and as well as AKI in other chronic liver diseases (non-HRS–AKI) so that early recognition of HRS–AKI and the appropriate management can be established.

Research progress of transfering mitochondria application in nanotubes in treatment of acute lung injury sepsis

Acute lung injury (ALI) is a common complication of sepsis with characteristics of acute onset, rapid change in the disease and high mortality. Since current clinical treatment can only alleviate the unfavorable condition to a certain extent but cure, we urgently need to find an effective treatment. Most scholars believe that sepsis-induced ALI is associated with extensive mitochondrial damage. In recent years, a widely studied pluripotent stem cell that is mesenchymal stem cell has been proved to alleviate and treat sepsis-induced ALI by transporting mitochondria via nanotubes in a microtubule-dependent manner. Research progress in this field will be reviewed in this study.

Study of the anti-inflammatory effect of the Traditional Mongolian Medicine Hohgardi-9 in acute lung injury

Background:Hohgardi-9 is a well-known traditional Mongolian drug that relieves cough and removes phlegm.Although it is widely used to treat lung diseases clinically,Hohgardi-9’s bioactive constituents and mechanism of action are unknown.In this study,we explored the bioactive compounds in Hohgardi-9 and the mechanism underlying its therapeutic effect against acute lung injury(ALI).Methods:We obtained the main components of Hohgardi-9 and analyzed the targets related to ALI by searching the traditional Chinese medicine systems pharmacology database and existing literature.Then,we constructed the compound-target network using Cytoscape 3.8.0 software to obtain the bioactive compounds in Hohgardi-9 against ALI.We used a string database to investigate the interaction between the possible protein targets of Hohgardi-9.We also performed Gene Ontology function annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis to predict its anti-ALI mechanism.Further,to verify the therapeutical effects of Hohgardi-9,we used an ALI rat model and analyzed the components of Hohgardi-9 found in the rat plasma using ultra-high-performance liquid chromatography coupled with Q-Exactive mass spectrometry.Results:The network pharmacology and plasma component analysis showed that Hohgardi-9 contained 31 potentially bioactive components,including quercetin,herbacetin,izoteolin,and columbinetin acetate,which affected the NF-κB,TLR,and TNF signaling pathways via key targets,such as RELA(p65)and TLR4.The in vivo experiments using hematoxylin and eosin staining revealed that Hohgardi-9 significantly improved lung tissue injury and pulmonary edema in ALI rats.Simultaneously,Hohgardi-9 significantly reduced the expression levels of genes encoding inflammatory factors,such as TRL4,TNF-α,IL-1β,and ICAM1,in the lungs of ALI rats.Conclusion:Hohgardi-9 alleviated ALI by inhibiting inflammation-related gene expression through its active ingredients,such as quercetin and herbacetin.