Objective:To observe the effects of sevoflurane treatment on lung inflammation in rats with lipopolysaccharide-induced acute lung injury(ALI).Methods:The rat model of ALI was established by intratracheal instillation ...Objective:To observe the effects of sevoflurane treatment on lung inflammation in rats with lipopolysaccharide-induced acute lung injury(ALI).Methods:The rat model of ALI was established by intratracheal instillation of lipopolysaccharide(LPS).45 infantile SD rats[body weight(272±15) g]were randomly divided into 3 groups(n=15):control group,LPS group, sevoflurane group.NS(1 mL/kg) was instillated in rats’airways of control group;LPS(5 mg/ kg) was instillated in rats’airways of LPS group.Sevoflurane group rats received sevoflurane (2.4%) inhalation for a hour after LPS was instillated in rats’airways.Six hours after NS or LPS instillation,all rats were exsanguinated.Lung tissues were examined by HE staining.Expressions of TNF-αand ICAM1 mRNA were detected by semiquantitative RT-PCR techniques.The protein level of TNF-αand ICAM1 were assessed by western blot techniques.Results:In LPS group the permeability of lung tissues increased,organizational structure severely damaged and the alveolar wall turned thick,with interstitial edema and Europhiles infiltrated increasingly.The LPS group had higher mRNA expressions of TNF-αand ICAM1 than control group and sevoflurane group (P【0.05),and LPS group had higher protein level of TNF-αand ICAMI than control group and sevoflurane group(P【0.05).Conclusions:Sevoflurane treatment can attenuate lung inflammation in rats with lipopolysaccharide-induced acute lung injury.展开更多
AIM: To study the changes of endogenous interleukin 18 (IL-18) levels and evaluate the role of IL-18 on lung injury following gut ischemia/reperfusion.METHODS: A superior mesenteric artery occlusion model was selected...AIM: To study the changes of endogenous interleukin 18 (IL-18) levels and evaluate the role of IL-18 on lung injury following gut ischemia/reperfusion.METHODS: A superior mesenteric artery occlusion model was selected for this research. The mice were randomly divided into four groups: Sham operation (sham), ischemia (0.5 h) followed by different times of reperfusion (I/R),and I/R pretreated with exogenous IL-18 (I/R+IL-18) or IL-18 neutralizing antibody (I/R+IL-18Ab) 15 min before ischemia. Serum IL-18 levels were detected by Western blot and ELISA, and the levels of IL-18 in lung tissue were evaluated by immunohistochemical staining. For the study of pulmonary inflammation, the lung myeloperoxidase (MPO) contents and morphological changes were evaluated.RESULTS: Gut ischemia/reperfusion induced rapid increase of serum IL-18 levels, peaked at 1 h after reperfusion and then declined. The levels of IL-18 in lung tissue were gradually enhanced as the progress of reperfusion.Compared with I/R group, exogenous administration of IL-18 (I/R+IL-18) further remarkably enhanced the pulmonary MPO activity and inflammatory cell infiltration,and in I/R+IL-18Ab group, the content of MPO were significantly reduced and lung inflammation was also decreased.CONCLUSION: Gut ischemia/reperfusion induces the increase of IL-18 expression, which may make IL-18 act as an important proinflammatory cytokine and contribute to gut ischemia/reperfusion-induced lung inflammation.展开更多
Severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)is the etiologic agent responsible for the global coronavirus disease 2019(COVID-19)pandemic.Numerous studies have demonstrated that cardiovascular disease m...Severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)is the etiologic agent responsible for the global coronavirus disease 2019(COVID-19)pandemic.Numerous studies have demonstrated that cardiovascular disease may affect COVID-19 progression.In the present study,we investigated the effect of hypertension on viral replication and COVID-19 progression using a hypertensive mouse model infected with SARS-Co V-2.Results revealed that SARS-Co V-2 replication was delayed in hypertensive mouse lungs.In contrast,SARS-Co V-2 replication in hypertensive mice treated with the antihypertensive drug captopril demonstrated similar virus replication as SARS-Co V-2-infected normotensive mice.展开更多
Allergic asthma is an inflammatory disease of the airways characterized by recurrent episodes of wheezing,bronchoconstriction,and airway hyperresponsiveness(AHR)[1].In recent years,allergic asthma has become a heated ...Allergic asthma is an inflammatory disease of the airways characterized by recurrent episodes of wheezing,bronchoconstriction,and airway hyperresponsiveness(AHR)[1].In recent years,allergic asthma has become a heated public health problem because of the highly increased incidence and prevalence[2].The main pathogenesis of asthma is airway inflammation and AHR.AHR is caused by an imbalance of Th1/Th2 cells with predominance to Th2,whereas airway inflammation is caused by increased levels of Th2 cytokine[3].Major effects of pathological changes in the respiratory include eosinophil infiltration,bronchial epithelial cell damage,obstruction of the mucus plug,and thickening of the submucosal muscle layer[4,5].展开更多
Excessive and uncontrollable inflammatory responses in alveoli can dramatically exacerbate pulmonary disease progressions through vigorous cytokine releases,immune cell infiltration and protease-driven tissue damages....Excessive and uncontrollable inflammatory responses in alveoli can dramatically exacerbate pulmonary disease progressions through vigorous cytokine releases,immune cell infiltration and protease-driven tissue damages.It is an urgent need to explore potential drug strategies for mitigating lung inflammation.Protease-activated receptor 2(PAR2)as a vital molecular target principally participates in various inflammatory diseases via intracellular signal transduction.However,it has been rarely reported about the role of PAR2 in lung inflammation.This study applied CRISPR-Cas9 system encoding Cas9 and sg RNA(p Cas9-PAR2)for PAR2 knockout and fabricated an anionic human serum albuminbased nanoparticles to deliver p Cas9-PAR2 with superior inflammation-targeting efficiency and stability(TAP/p Cas9-PAR2).TAP/p Cas9-PAR2 robustly facilitated p Cas9-PAR2 to enter and transfect inflammatory cells,eliciting precise gene editing of PAR2 in vitro and in vivo.Importantly,PAR2 deficiency by TAP/p Cas9-PAR2 effectively and safely promoted macrophage polarization,suppressed proinflammatory cytokine releases and alleviated acute lung inflammation,uncovering a novel value of PAR2.It also revealed that PAR2-mediated pulmonary inflammation prevented by TAP/p Cas9-PAR2was mainly dependent on ERK-mediated NLRP3/IL-1β and NO/i NOS signalling.Therefore,this work indicated PAR2 as a novel target for lung inflammation and provided a potential nanodrug strategy for PAR2 deficiency in treating inflammatory diseases.展开更多
Group 2 innate lymphoid cells(ILC2s)are a category of heterogeneous cells that produce the cytokines IL-5 and IL-13,which mediate the type 2 immune response.However,specific drug targets on lung ILC2s have rarely been...Group 2 innate lymphoid cells(ILC2s)are a category of heterogeneous cells that produce the cytokines IL-5 and IL-13,which mediate the type 2 immune response.However,specific drug targets on lung ILC2s have rarely been reported.Previous studies have shown that type 2 cytokines,such as IL-5 and IL-13,are related to depression.Here,we demonstrated the negative correlation between the depression-associated monoamine neurotransmitter serotonin and secretion of the cytokines IL-5 and IL-13 by ILC2s in individuals with depression.Interestingly,serotonin ameliorates papain-induced lung inflammation by suppressing ILC2 activation.Our data showed that the serotonin receptor HTR2A was highly expressed on ILC2s from mouse lungs and human PBMCs.Furthermore,an HTR2A selective agonist(DOI)impaired ILC2 activation and alleviated the type 2 immune response in vivo and in vitro.Mice with ILC2-specific depletion of HTR2A(Il5^(cre/+)·Htr2a^(flox/flox)mice)abolished the DOI-mediated inhibition of ILC2s in a papain-induced mouse model of inflammation.In conclusion,serotonin and DOI could restrict the type 2 lung immune response,indicating a potential treatment strategy for type 2 lung inflammation by targeting HTR2A on ST2+ILC2s.展开更多
Inhaled nanoparticles(NPs)need to penetrate the bronchial mucosa to deliver drug payloads deeply in the lung for amplified local therapy.However,the bronchial mucociliary barrier eliminates NPs rapidly,which considera...Inhaled nanoparticles(NPs)need to penetrate the bronchial mucosa to deliver drug payloads deeply in the lung for amplified local therapy.However,the bronchial mucociliary barrier eliminates NPs rapidly,which considerably limits their mucosal penetration.In this study,we find that surface ligand modification and stiffness adjustment of NPs contribute to the significantly enhanced bronchial mucosal absorption and pulmonary retention of inhaled drugs.We utilize neonatal Fc receptor ligand(FcBP)to modify the rationally designed low stiffness NPs(Soft-NP)and high stiffness NPs(Stiff-NP)to target bronchial mucosa.In an acute lung inflammation rat model,after intranasal administration with dexamethasone-loaded NPs,Stiff-NP endowed with FcBP displays superior therapeutic effects.The in vitro data demonstrate that the promotion effect of FcBP to bronchial mucosal absorption of Stiff-NP dominates over Soft-NP.This could be attributed to the higher affinity between ligand-receptor when incorporating FcBP on the Stiff-NP surface.Meanwhile,high stiffness modulates more actin filaments aggregation to mediate endocytosis,along with strengthened Ca2+signal to enhance exocytosis.Conclusively,we highlight that FcBP-modified NPs with higher stiffness would be a potential pulmonary drug delivery system.展开更多
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 u...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.展开更多
To the Editor:Lung fibrosis is characterized by extracellular matrix accumulation and remodeling of the lung interstitium.Although lung fibrosis has been extensively studied,there is still a lack of effective anti-pul...To the Editor:Lung fibrosis is characterized by extracellular matrix accumulation and remodeling of the lung interstitium.Although lung fibrosis has been extensively studied,there is still a lack of effective anti-pulmonary fibrosis drugs at present.The pathogenesis of lung fibrosis involves many aspects in which the lung macrophages play a particularly important role.[1]It has been reported that the manipulation of the monocyte/macrophage phenotype switch might be a potential target for many macrophagemediated inflammatory disorders.In our previous study,mice that were exposed to bleomycin(BLM)showed a dynamic change of mononuclear phagocytes in the circulating system,lung alveoli,and interstitial compartments.The rapid increase of the number of circulating Ly6Chi monocytes after BLM stimulation,followed by the expansion of M2-like alveolar macrophages(AMf)numbers,is closely associated with lung inflammatory response and fibrosis.[2,3]展开更多
Lung inflammation is an essential inducer of various diseases and is closely related to pulmonary-endothelium dysfunction.Herein,we propose a pulmonary endothelium-targeted codelivery system of anti-inflammatory indom...Lung inflammation is an essential inducer of various diseases and is closely related to pulmonary-endothelium dysfunction.Herein,we propose a pulmonary endothelium-targeted codelivery system of anti-inflammatory indomethacin(IND)and antioxidant superoxide dismutase(SOD)by assembling the biopharmaceutical SOD onto the“vector”of rod-like pure IND crystals,followed by coating with anti-ICAM-1 antibody(Ab)for targeting endothelial cells.The codelivery system has a 237 nm diameter in length and extremely high drug loading of 39%IND and 2.3%SOD.Pharmacokinetics and biodistribution studies demonstrate the extended blood circulation and the strong pulmonary accumulation of the system after intravenous injection in the lipopolysaccharide(LPS)-induced inflammatory murine model.Particularly,the system allows a robust capacity to target pulmonary endothelium mostly due to the rod-shape and Ab coating effect.In vitro,the preparation shows the synergistic antiinflammatory and antioxidant effects in LPS-activated endothelial cells.In vivo,the preparation exhibits superior pharmacodynamic efficacy revealed by significantly downregulating the inflammatory/oxidative stress markers,such as TNF-a,IL-6,COX-2,and reactive oxygen species(ROS),in the lungs.In conclusion,the codelivery system based on rod-like pure crystals could well target the pulmonary endothelium and effectively alleviate lung inflammation.The study offers a promising approach to combat pulmonary endothelium-associated diseases.展开更多
It has been known for some time that low PLP blood levels are common in asthmatic patients,and supplementation with vitamin B6 may reduce the severity of asthma symptoms[12].In the current study,a comparison of PLP le...It has been known for some time that low PLP blood levels are common in asthmatic patients,and supplementation with vitamin B6 may reduce the severity of asthma symptoms[12].In the current study,a comparison of PLP levels in the plasma of asthmatic patients(n=52)and healthy controls(n=58)confirmed lower PLP concentrations in asthmatic patients,which correlated with reduced lung function and increased circulating eosinophils,suggestive of increased type 2 inflammation.Using several mouse models of acute lung inflammation,they confirmed that systemic or local administration of PLP reduced lung inflammation and eosinophil density,suggesting that PLP concentration may be directly controlling immune responses that lead to the development of allergic airway disease.ILC2s constitutively express ST2,and IL-33 profoundly promotes ILC2 expansion and secretion of IL-5 and IL-13 to mediate allergic reactions and support host defenses against parasitic worms.PLP reduces the number of type 2 innate lymphoid cells(ILC2s)and their expression of IL-5 and IL-13.Conversely,diet-induced vitamin B6 deficiency in mice increased papain-induced lung inflammation,including increasing the proportion of IL5+and IL-13+ILC2s.The authors revealed that PLP treatment decreased IL-33 levels in the bronchoalveolar lavage fluid(BALF)and lung and targeting IL-33 with an antibody during papain-induced lung inflammation did not reduce inflammation beyond that of PLP treatment alone.An important clue to the regulation of IL-33 was that PLP treatment did not modify IL-33 mRNA levels.Instead,pyridoxal(PL)treatment of a human alveolar basal epithelial cell line(A549)stably expressing full-length IL-33 with a hemagglutinin(HA)tag established that PL exposure potently decreased intracellular IL-33 protein levels.The researchers used this cell line to explore the underlying mechanisms and verified that PL conversion to PLP by pyridoxal kinase(PDXK)controlled the stability of IL-33.Consistent with these data,the IL-33 concentration and papain-induced lung inflammation were augmented significantly in PDXK-deficient mice.The author’s use of degradative pathway inhibitors and truncated IL-33 constructs pinpointed a mechanism involving protective ubiquitylation of the IL-33 N-terminal domain that is inhibited by vitamin B6.A comprehensive database search for proteome-wide known and predicted ubiquitin ligase/deubiquitinase-substrate interactions showed that mouse double minute 2 homolog(MDM2)was a likely E3 ubiquitin ligase interacting with IL-33.Recent studies have shown that MDM2,while best known for its regulation of p53,mediates the ubiquitination and stability of numerous nuclear proteins,including Foxp3,HDACs,and STATs[13,14,15].In the current work,MDM2 interacted with IL-33 via a RING domain to facilitate IL-33 stability via ubiquitination of lysines to control IL-33 homeostasis,and this ubiquitination could be inhibited by vitamin B6(Fig.2).It will be important for future studies to establish how precisely PLP suppresses the functional interactions between IL-33 and MDM2.展开更多
Local ischemia often causes a series of inflammatory reactions when both brain immune cells and the peripheral immune response are activated.In the human body,the gut and lung are regarded as the key reactional target...Local ischemia often causes a series of inflammatory reactions when both brain immune cells and the peripheral immune response are activated.In the human body,the gut and lung are regarded as the key reactional targets that are initiated by brain ischemic attacks.Mucosal microorganisms play an important role in immune regulation and metabolism and affect blood-brain barrier permeability.In addition to the relationship between peripheral organs and central areas and the intestine and lung also interact among each other.Here,we review the molecular and cellular immune mechanisms involved in the pathways of inflammation across the gut-brain axis and lung-brain axis.We found that abnormal intestinal flora,the intestinal microenvironment,lung infection,chronic diseases,and mechanical ventilation can worsen the outcome of ischemic stroke.This review also introduces the influence of the brain on the gut and lungs after stroke,highlighting the bidirectional feedback effect among the gut,lungs,and brain.展开更多
Brain organoids mimic closely the embryonic human brain:Over the last decade,the development of human organoid systems has evolved rapidly.Different tissues have been modeled with organoids,such as the gut,lung,liver,...Brain organoids mimic closely the embryonic human brain:Over the last decade,the development of human organoid systems has evolved rapidly.Different tissues have been modeled with organoids,such as the gut,lung,liver,kidney retina and brain.These systems have a high cellular heterogeneity,with many cell types integrated into the same system.Organoids'cellular populations interact between and amongst each other in a cellular and molecular level,which represents an advantage with respects to monolayer 2D cell culture systems.展开更多
In neurodegenerative and classically demyelinating disorders such as multiple sclerosis(MS),spinal cord injury(SCI),stroke,and Charcot-Marie-Tooth disease,glial functioning is compromised and nervous tissue integrity ...In neurodegenerative and classically demyelinating disorders such as multiple sclerosis(MS),spinal cord injury(SCI),stroke,and Charcot-Marie-Tooth disease,glial functioning is compromised and nervous tissue integrity is lost.Recently,primary neurodegenerative disorders such as Alzheimer’s disease,amyotrophic lateral sclerosis(ALS),and Parkinson’s disease(PD)are increasingly linked to impaired oligodendroglia functioning upon neurodegeneration.Due to the destructive micro-environment created by nervous tissue damage,the progressive cellular loss in these disorders,and the amitotic nature of neurons,spontaneous endogenous repair process are limited in nature.Hence,there is a medical need for efficient therapeutic strategies capable of supporting neuro-reparative processes to occur,likely supported by improved oligodendroglia cell functioning.展开更多
BACKGROUND:Prolonged invasive respiratory support and extracorporeal membrane oxygenation(ECMO)in patients requiring urgent lung transplantation(ULTx)present signifi cant challenges to clinical practice due to severe ...BACKGROUND:Prolonged invasive respiratory support and extracorporeal membrane oxygenation(ECMO)in patients requiring urgent lung transplantation(ULTx)present signifi cant challenges to clinical practice due to severe underlying diseases and complex conditions.The aim of the study was to report the clinical outcomes of patients who received ULTx and followed the perioperative rehabilitation protocol implemented in a lung transplant center.METHODS:A retrospective analysis was conducted in ULTx patients who required preoperative invasive mechanical ventilation(IMV)and ECMO between January 2018 and January 2023.Data were retrieved from electronic medical records at our lung transplant center.RESULTS:Fourteen patients(mean age 57.43±10.97 years;12 males,2 females)underwent ULTx with bridging ECMO and IMV.The mean body mass index was 23.94±3.33 kg/m²,and the mean Acute Physiology and Chronic Health Evaluation(APACHE)II score was 21.50±3.96.The Nutritional Risk Screening 2002(NRS 2002)scores were≥3.ULTx was performed after an 8.5-day waiting period(interquartile interval[IQR]5.0-26.5 d).Following the surgeries,the average lengths of ECMO and IMV were 1.0(IQR 1.0-2.0)d and 5.0(IQR 3.0-7.3)d,respectively.The total length of hospital stay was 60.1±30.8 d,with an average intensive care unit stay of 38.3±22.9 d and post-operative hospitalization stay of 45.8±26.1 d.Two patients died within 30 d after ULTx,with a 30-day survival rate of 85.71%.CONCLUSION:Patients receiving ULTx showed an acceptable short-term survival rate,validating the practicality and safety of the treatment protocols implemented in our center.展开更多
Pre-diabetic insulin resistance is associated with sub-clinical inflammation and concomitant increase in systemic C-reactive protein(CRP)levels.Type 2 diabetes mellitus(T2DM)patients register even higher chronic level...Pre-diabetic insulin resistance is associated with sub-clinical inflammation and concomitant increase in systemic C-reactive protein(CRP)levels.Type 2 diabetes mellitus(T2DM)patients register even higher chronic levels of inflammation,with excess circulating CRP originating from both typical hepatic synthesis,and also visceral white adipose tissue.展开更多
Global Cancer Statistics 2022 reported the prevalence and high mortality rate of lung cancer.Notably,non-small cell lung cancer(NSCLC)accounts for the majority of the histologic types1.Precision therapy for lung cance...Global Cancer Statistics 2022 reported the prevalence and high mortality rate of lung cancer.Notably,non-small cell lung cancer(NSCLC)accounts for the majority of the histologic types1.Precision therapy for lung cancer has progressed rapidly and immune checkpoint inhibitors(ICIs)have become a leading research topic.Indeed,ICI therapy has been shown to improve the prognosis of lung cancer patients.展开更多
BACKGROUND There are few cases of pulmonary granulomatous changes secondary to primary biliary cirrhosis(PBC).No case of granulomatous lung disease secondary to PBC misdiagnosed as lung cancer had been reported.CASE S...BACKGROUND There are few cases of pulmonary granulomatous changes secondary to primary biliary cirrhosis(PBC).No case of granulomatous lung disease secondary to PBC misdiagnosed as lung cancer had been reported.CASE SUMMARY A middle-aged woman presented with lung nodules and was misdiagnosed with lung cancer by positron emission tomography/computed tomography.She underwent left lobectomy,and the pathology of the nodules showed granulomatous inflammation,which was then treated with antibiotics.However,a new nodule appeared.Further investigation with lung biopsy and liver serology led to the diagnosis of PBC,and chest computed tomography indicated significant reduction in the pulmonary nodule by treatment with methylprednisolone and ursodeoxycholic acid.CONCLUSION Diagnosis of pulmonary nodules requires integrating various clinical data to avoid unnecessary pulmonary lobectomy.展开更多
Dear Editor,Lung adenocarcinoma with choroidal metastasis is a common form of cancer,with breast cancer accounting for 40%-53%and lung cancer accounting for 20%-29%of primary cases with choroidal metastases[1].This ty...Dear Editor,Lung adenocarcinoma with choroidal metastasis is a common form of cancer,with breast cancer accounting for 40%-53%and lung cancer accounting for 20%-29%of primary cases with choroidal metastases[1].This type of metastatic cancer typically affects people aged 40-70y,and is more prevalent in women than men[1].Ocular symptoms,including vision loss,can be an early indication of the disease,as many tumors are asymptomatic in their early stages.Studies have shown that 40.3%of cases involve the macular region,which explains why ocular symptoms are often the first manifestation of the disease[2].When choroidal metastasis is suspected in patients without a history of cancer,a combination of diagnostic tools should be used to identify the primary source of the tumor.Choroidal tumors can serve as an indication of future lung cancer diagnosis in some patients with lung cancer[1].In this report,we present a case of bilateral lung adenocarcinoma where ocular symptoms were the first indication of the disease.展开更多
基金Supported by Henan Province health science and technology creative talents innovation talents Foundation(Grant No.20114155)
文摘Objective:To observe the effects of sevoflurane treatment on lung inflammation in rats with lipopolysaccharide-induced acute lung injury(ALI).Methods:The rat model of ALI was established by intratracheal instillation of lipopolysaccharide(LPS).45 infantile SD rats[body weight(272±15) g]were randomly divided into 3 groups(n=15):control group,LPS group, sevoflurane group.NS(1 mL/kg) was instillated in rats’airways of control group;LPS(5 mg/ kg) was instillated in rats’airways of LPS group.Sevoflurane group rats received sevoflurane (2.4%) inhalation for a hour after LPS was instillated in rats’airways.Six hours after NS or LPS instillation,all rats were exsanguinated.Lung tissues were examined by HE staining.Expressions of TNF-αand ICAM1 mRNA were detected by semiquantitative RT-PCR techniques.The protein level of TNF-αand ICAM1 were assessed by western blot techniques.Results:In LPS group the permeability of lung tissues increased,organizational structure severely damaged and the alveolar wall turned thick,with interstitial edema and Europhiles infiltrated increasingly.The LPS group had higher mRNA expressions of TNF-αand ICAM1 than control group and sevoflurane group (P【0.05),and LPS group had higher protein level of TNF-αand ICAMI than control group and sevoflurane group(P【0.05).Conclusions:Sevoflurane treatment can attenuate lung inflammation in rats with lipopolysaccharide-induced acute lung injury.
基金Supported by the CAS Pilot Project of Knowledge Innovation Program, No. KSCX 2-3-04-03
文摘AIM: To study the changes of endogenous interleukin 18 (IL-18) levels and evaluate the role of IL-18 on lung injury following gut ischemia/reperfusion.METHODS: A superior mesenteric artery occlusion model was selected for this research. The mice were randomly divided into four groups: Sham operation (sham), ischemia (0.5 h) followed by different times of reperfusion (I/R),and I/R pretreated with exogenous IL-18 (I/R+IL-18) or IL-18 neutralizing antibody (I/R+IL-18Ab) 15 min before ischemia. Serum IL-18 levels were detected by Western blot and ELISA, and the levels of IL-18 in lung tissue were evaluated by immunohistochemical staining. For the study of pulmonary inflammation, the lung myeloperoxidase (MPO) contents and morphological changes were evaluated.RESULTS: Gut ischemia/reperfusion induced rapid increase of serum IL-18 levels, peaked at 1 h after reperfusion and then declined. The levels of IL-18 in lung tissue were gradually enhanced as the progress of reperfusion.Compared with I/R group, exogenous administration of IL-18 (I/R+IL-18) further remarkably enhanced the pulmonary MPO activity and inflammatory cell infiltration,and in I/R+IL-18Ab group, the content of MPO were significantly reduced and lung inflammation was also decreased.CONCLUSION: Gut ischemia/reperfusion induces the increase of IL-18 expression, which may make IL-18 act as an important proinflammatory cytokine and contribute to gut ischemia/reperfusion-induced lung inflammation.
基金supported by the National Key R&D Program of China(2020YFC0842000)National Natural Science Foundation of China(81960662)Science and Technology Department of Yunnan Province(202001AS070034)。
文摘Severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)is the etiologic agent responsible for the global coronavirus disease 2019(COVID-19)pandemic.Numerous studies have demonstrated that cardiovascular disease may affect COVID-19 progression.In the present study,we investigated the effect of hypertension on viral replication and COVID-19 progression using a hypertensive mouse model infected with SARS-Co V-2.Results revealed that SARS-Co V-2 replication was delayed in hypertensive mouse lungs.In contrast,SARS-Co V-2 replication in hypertensive mice treated with the antihypertensive drug captopril demonstrated similar virus replication as SARS-Co V-2-infected normotensive mice.
基金supported by the National Natural Science Foundation of China[Grant Nos.31971562 and 81671586].
文摘Allergic asthma is an inflammatory disease of the airways characterized by recurrent episodes of wheezing,bronchoconstriction,and airway hyperresponsiveness(AHR)[1].In recent years,allergic asthma has become a heated public health problem because of the highly increased incidence and prevalence[2].The main pathogenesis of asthma is airway inflammation and AHR.AHR is caused by an imbalance of Th1/Th2 cells with predominance to Th2,whereas airway inflammation is caused by increased levels of Th2 cytokine[3].Major effects of pathological changes in the respiratory include eosinophil infiltration,bronchial epithelial cell damage,obstruction of the mucus plug,and thickening of the submucosal muscle layer[4,5].
基金supported by the National Natural Science Foundation of China(Nos.82003784 and 81872789)the Fundamental Research Funds for the Central Universities(No.2682022ZTPY037,China)Large Instruments Open Foundation of Southwest Jiaotong University(No.2022SRII-046,China)。
文摘Excessive and uncontrollable inflammatory responses in alveoli can dramatically exacerbate pulmonary disease progressions through vigorous cytokine releases,immune cell infiltration and protease-driven tissue damages.It is an urgent need to explore potential drug strategies for mitigating lung inflammation.Protease-activated receptor 2(PAR2)as a vital molecular target principally participates in various inflammatory diseases via intracellular signal transduction.However,it has been rarely reported about the role of PAR2 in lung inflammation.This study applied CRISPR-Cas9 system encoding Cas9 and sg RNA(p Cas9-PAR2)for PAR2 knockout and fabricated an anionic human serum albuminbased nanoparticles to deliver p Cas9-PAR2 with superior inflammation-targeting efficiency and stability(TAP/p Cas9-PAR2).TAP/p Cas9-PAR2 robustly facilitated p Cas9-PAR2 to enter and transfect inflammatory cells,eliciting precise gene editing of PAR2 in vitro and in vivo.Importantly,PAR2 deficiency by TAP/p Cas9-PAR2 effectively and safely promoted macrophage polarization,suppressed proinflammatory cytokine releases and alleviated acute lung inflammation,uncovering a novel value of PAR2.It also revealed that PAR2-mediated pulmonary inflammation prevented by TAP/p Cas9-PAR2was mainly dependent on ERK-mediated NLRP3/IL-1β and NO/i NOS signalling.Therefore,this work indicated PAR2 as a novel target for lung inflammation and provided a potential nanodrug strategy for PAR2 deficiency in treating inflammatory diseases.
基金the Ministry of Science and Technology of China(2018YFA0507402)the National Natural Science Foundation of China(32000667)+5 种基金the Shanghai Science and Technology Innovation Action(21ZR1470600)the Youth Innovation Promotion Association of the Chinese Academy of Sciences(2022264)the National Natural Science Foundation of China(81771465 and 81930033)the Science and Technology Project of the Department of Education of Jiangxi Province(GJJ211248)the Division of Intramural Research,National Institute of Allergy and Infectious Diseases,National Institutes of Health(grant 1ZIA-Al-001169)the US-China Biomedical Collaborative Research Program(grant Al-129775).
文摘Group 2 innate lymphoid cells(ILC2s)are a category of heterogeneous cells that produce the cytokines IL-5 and IL-13,which mediate the type 2 immune response.However,specific drug targets on lung ILC2s have rarely been reported.Previous studies have shown that type 2 cytokines,such as IL-5 and IL-13,are related to depression.Here,we demonstrated the negative correlation between the depression-associated monoamine neurotransmitter serotonin and secretion of the cytokines IL-5 and IL-13 by ILC2s in individuals with depression.Interestingly,serotonin ameliorates papain-induced lung inflammation by suppressing ILC2 activation.Our data showed that the serotonin receptor HTR2A was highly expressed on ILC2s from mouse lungs and human PBMCs.Furthermore,an HTR2A selective agonist(DOI)impaired ILC2 activation and alleviated the type 2 immune response in vivo and in vitro.Mice with ILC2-specific depletion of HTR2A(Il5^(cre/+)·Htr2a^(flox/flox)mice)abolished the DOI-mediated inhibition of ILC2s in a papain-induced mouse model of inflammation.In conclusion,serotonin and DOI could restrict the type 2 lung immune response,indicating a potential treatment strategy for type 2 lung inflammation by targeting HTR2A on ST2+ILC2s.
基金support from the National Science Foundation for Distinguished Yong Scholars(81625023)the National Natural Science Foundation of China(81872818).
文摘Inhaled nanoparticles(NPs)need to penetrate the bronchial mucosa to deliver drug payloads deeply in the lung for amplified local therapy.However,the bronchial mucociliary barrier eliminates NPs rapidly,which considerably limits their mucosal penetration.In this study,we find that surface ligand modification and stiffness adjustment of NPs contribute to the significantly enhanced bronchial mucosal absorption and pulmonary retention of inhaled drugs.We utilize neonatal Fc receptor ligand(FcBP)to modify the rationally designed low stiffness NPs(Soft-NP)and high stiffness NPs(Stiff-NP)to target bronchial mucosa.In an acute lung inflammation rat model,after intranasal administration with dexamethasone-loaded NPs,Stiff-NP endowed with FcBP displays superior therapeutic effects.The in vitro data demonstrate that the promotion effect of FcBP to bronchial mucosal absorption of Stiff-NP dominates over Soft-NP.This could be attributed to the higher affinity between ligand-receptor when incorporating FcBP on the Stiff-NP surface.Meanwhile,high stiffness modulates more actin filaments aggregation to mediate endocytosis,along with strengthened Ca2+signal to enhance exocytosis.Conclusively,we highlight that FcBP-modified NPs with higher stiffness would be a potential pulmonary drug delivery system.
基金This study was funded in part by the National Natural Science Foundation of China(Nos.31861143050,31772476 and 31911530077).
文摘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.
基金supported by a grant from Tianjin Municipal Science and Technology Committee(No.18JCZDJC12000).
文摘To the Editor:Lung fibrosis is characterized by extracellular matrix accumulation and remodeling of the lung interstitium.Although lung fibrosis has been extensively studied,there is still a lack of effective anti-pulmonary fibrosis drugs at present.The pathogenesis of lung fibrosis involves many aspects in which the lung macrophages play a particularly important role.[1]It has been reported that the manipulation of the monocyte/macrophage phenotype switch might be a potential target for many macrophagemediated inflammatory disorders.In our previous study,mice that were exposed to bleomycin(BLM)showed a dynamic change of mononuclear phagocytes in the circulating system,lung alveoli,and interstitial compartments.The rapid increase of the number of circulating Ly6Chi monocytes after BLM stimulation,followed by the expansion of M2-like alveolar macrophages(AMf)numbers,is closely associated with lung inflammatory response and fibrosis.[2,3]
基金supported by the National Natural Science Foundation of China,China (Nos.81872823,82073782 and 82241002)the Shanghai Science and Technology Committee,China (No.19430741500)the Key Laboratory of Modern Chinese Medicine Preparation of Ministry of Education of Jiangxi University of Traditional Chinese Medicine,China (zdsys202103)。
文摘Lung inflammation is an essential inducer of various diseases and is closely related to pulmonary-endothelium dysfunction.Herein,we propose a pulmonary endothelium-targeted codelivery system of anti-inflammatory indomethacin(IND)and antioxidant superoxide dismutase(SOD)by assembling the biopharmaceutical SOD onto the“vector”of rod-like pure IND crystals,followed by coating with anti-ICAM-1 antibody(Ab)for targeting endothelial cells.The codelivery system has a 237 nm diameter in length and extremely high drug loading of 39%IND and 2.3%SOD.Pharmacokinetics and biodistribution studies demonstrate the extended blood circulation and the strong pulmonary accumulation of the system after intravenous injection in the lipopolysaccharide(LPS)-induced inflammatory murine model.Particularly,the system allows a robust capacity to target pulmonary endothelium mostly due to the rod-shape and Ab coating effect.In vitro,the preparation shows the synergistic antiinflammatory and antioxidant effects in LPS-activated endothelial cells.In vivo,the preparation exhibits superior pharmacodynamic efficacy revealed by significantly downregulating the inflammatory/oxidative stress markers,such as TNF-a,IL-6,COX-2,and reactive oxygen species(ROS),in the lungs.In conclusion,the codelivery system based on rod-like pure crystals could well target the pulmonary endothelium and effectively alleviate lung inflammation.The study offers a promising approach to combat pulmonary endothelium-associated diseases.
基金supported by funding from the National Institutes of Health(R01HL22489 and R01AR073527)the Department of Defense(W81XWH-21–1–0896).
文摘It has been known for some time that low PLP blood levels are common in asthmatic patients,and supplementation with vitamin B6 may reduce the severity of asthma symptoms[12].In the current study,a comparison of PLP levels in the plasma of asthmatic patients(n=52)and healthy controls(n=58)confirmed lower PLP concentrations in asthmatic patients,which correlated with reduced lung function and increased circulating eosinophils,suggestive of increased type 2 inflammation.Using several mouse models of acute lung inflammation,they confirmed that systemic or local administration of PLP reduced lung inflammation and eosinophil density,suggesting that PLP concentration may be directly controlling immune responses that lead to the development of allergic airway disease.ILC2s constitutively express ST2,and IL-33 profoundly promotes ILC2 expansion and secretion of IL-5 and IL-13 to mediate allergic reactions and support host defenses against parasitic worms.PLP reduces the number of type 2 innate lymphoid cells(ILC2s)and their expression of IL-5 and IL-13.Conversely,diet-induced vitamin B6 deficiency in mice increased papain-induced lung inflammation,including increasing the proportion of IL5+and IL-13+ILC2s.The authors revealed that PLP treatment decreased IL-33 levels in the bronchoalveolar lavage fluid(BALF)and lung and targeting IL-33 with an antibody during papain-induced lung inflammation did not reduce inflammation beyond that of PLP treatment alone.An important clue to the regulation of IL-33 was that PLP treatment did not modify IL-33 mRNA levels.Instead,pyridoxal(PL)treatment of a human alveolar basal epithelial cell line(A549)stably expressing full-length IL-33 with a hemagglutinin(HA)tag established that PL exposure potently decreased intracellular IL-33 protein levels.The researchers used this cell line to explore the underlying mechanisms and verified that PL conversion to PLP by pyridoxal kinase(PDXK)controlled the stability of IL-33.Consistent with these data,the IL-33 concentration and papain-induced lung inflammation were augmented significantly in PDXK-deficient mice.The author’s use of degradative pathway inhibitors and truncated IL-33 constructs pinpointed a mechanism involving protective ubiquitylation of the IL-33 N-terminal domain that is inhibited by vitamin B6.A comprehensive database search for proteome-wide known and predicted ubiquitin ligase/deubiquitinase-substrate interactions showed that mouse double minute 2 homolog(MDM2)was a likely E3 ubiquitin ligase interacting with IL-33.Recent studies have shown that MDM2,while best known for its regulation of p53,mediates the ubiquitination and stability of numerous nuclear proteins,including Foxp3,HDACs,and STATs[13,14,15].In the current work,MDM2 interacted with IL-33 via a RING domain to facilitate IL-33 stability via ubiquitination of lysines to control IL-33 homeostasis,and this ubiquitination could be inhibited by vitamin B6(Fig.2).It will be important for future studies to establish how precisely PLP suppresses the functional interactions between IL-33 and MDM2.
基金supported by the National Natural Science Foundation of China,No.82204663the Natural Science Foundation of Shandong Province,No.ZR2022QH058(both to TZ).
文摘Local ischemia often causes a series of inflammatory reactions when both brain immune cells and the peripheral immune response are activated.In the human body,the gut and lung are regarded as the key reactional targets that are initiated by brain ischemic attacks.Mucosal microorganisms play an important role in immune regulation and metabolism and affect blood-brain barrier permeability.In addition to the relationship between peripheral organs and central areas and the intestine and lung also interact among each other.Here,we review the molecular and cellular immune mechanisms involved in the pathways of inflammation across the gut-brain axis and lung-brain axis.We found that abnormal intestinal flora,the intestinal microenvironment,lung infection,chronic diseases,and mechanical ventilation can worsen the outcome of ischemic stroke.This review also introduces the influence of the brain on the gut and lungs after stroke,highlighting the bidirectional feedback effect among the gut,lungs,and brain.
文摘Brain organoids mimic closely the embryonic human brain:Over the last decade,the development of human organoid systems has evolved rapidly.Different tissues have been modeled with organoids,such as the gut,lung,liver,kidney retina and brain.These systems have a high cellular heterogeneity,with many cell types integrated into the same system.Organoids'cellular populations interact between and amongst each other in a cellular and molecular level,which represents an advantage with respects to monolayer 2D cell culture systems.
文摘In neurodegenerative and classically demyelinating disorders such as multiple sclerosis(MS),spinal cord injury(SCI),stroke,and Charcot-Marie-Tooth disease,glial functioning is compromised and nervous tissue integrity is lost.Recently,primary neurodegenerative disorders such as Alzheimer’s disease,amyotrophic lateral sclerosis(ALS),and Parkinson’s disease(PD)are increasingly linked to impaired oligodendroglia functioning upon neurodegeneration.Due to the destructive micro-environment created by nervous tissue damage,the progressive cellular loss in these disorders,and the amitotic nature of neurons,spontaneous endogenous repair process are limited in nature.Hence,there is a medical need for efficient therapeutic strategies capable of supporting neuro-reparative processes to occur,likely supported by improved oligodendroglia cell functioning.
文摘BACKGROUND:Prolonged invasive respiratory support and extracorporeal membrane oxygenation(ECMO)in patients requiring urgent lung transplantation(ULTx)present signifi cant challenges to clinical practice due to severe underlying diseases and complex conditions.The aim of the study was to report the clinical outcomes of patients who received ULTx and followed the perioperative rehabilitation protocol implemented in a lung transplant center.METHODS:A retrospective analysis was conducted in ULTx patients who required preoperative invasive mechanical ventilation(IMV)and ECMO between January 2018 and January 2023.Data were retrieved from electronic medical records at our lung transplant center.RESULTS:Fourteen patients(mean age 57.43±10.97 years;12 males,2 females)underwent ULTx with bridging ECMO and IMV.The mean body mass index was 23.94±3.33 kg/m²,and the mean Acute Physiology and Chronic Health Evaluation(APACHE)II score was 21.50±3.96.The Nutritional Risk Screening 2002(NRS 2002)scores were≥3.ULTx was performed after an 8.5-day waiting period(interquartile interval[IQR]5.0-26.5 d).Following the surgeries,the average lengths of ECMO and IMV were 1.0(IQR 1.0-2.0)d and 5.0(IQR 3.0-7.3)d,respectively.The total length of hospital stay was 60.1±30.8 d,with an average intensive care unit stay of 38.3±22.9 d and post-operative hospitalization stay of 45.8±26.1 d.Two patients died within 30 d after ULTx,with a 30-day survival rate of 85.71%.CONCLUSION:Patients receiving ULTx showed an acceptable short-term survival rate,validating the practicality and safety of the treatment protocols implemented in our center.
文摘Pre-diabetic insulin resistance is associated with sub-clinical inflammation and concomitant increase in systemic C-reactive protein(CRP)levels.Type 2 diabetes mellitus(T2DM)patients register even higher chronic levels of inflammation,with excess circulating CRP originating from both typical hepatic synthesis,and also visceral white adipose tissue.
基金the Hunan Lung Cancer Clinical Medical Research Center(Grant No.2023SK4024 to LW)the Hunan Science and Technology Innovation Program(Grant No.2021SK51121 to LW)the Hunan Cancer Hospital Climb plan(Grant No.ZX2020005-5 to LW)。
文摘Global Cancer Statistics 2022 reported the prevalence and high mortality rate of lung cancer.Notably,non-small cell lung cancer(NSCLC)accounts for the majority of the histologic types1.Precision therapy for lung cancer has progressed rapidly and immune checkpoint inhibitors(ICIs)have become a leading research topic.Indeed,ICI therapy has been shown to improve the prognosis of lung cancer patients.
基金The Special Health Project of the Department of Finance of Jilin Province,China,No.2020SCZT023 and No.3D5177713429.
文摘BACKGROUND There are few cases of pulmonary granulomatous changes secondary to primary biliary cirrhosis(PBC).No case of granulomatous lung disease secondary to PBC misdiagnosed as lung cancer had been reported.CASE SUMMARY A middle-aged woman presented with lung nodules and was misdiagnosed with lung cancer by positron emission tomography/computed tomography.She underwent left lobectomy,and the pathology of the nodules showed granulomatous inflammation,which was then treated with antibiotics.However,a new nodule appeared.Further investigation with lung biopsy and liver serology led to the diagnosis of PBC,and chest computed tomography indicated significant reduction in the pulmonary nodule by treatment with methylprednisolone and ursodeoxycholic acid.CONCLUSION Diagnosis of pulmonary nodules requires integrating various clinical data to avoid unnecessary pulmonary lobectomy.
文摘Dear Editor,Lung adenocarcinoma with choroidal metastasis is a common form of cancer,with breast cancer accounting for 40%-53%and lung cancer accounting for 20%-29%of primary cases with choroidal metastases[1].This type of metastatic cancer typically affects people aged 40-70y,and is more prevalent in women than men[1].Ocular symptoms,including vision loss,can be an early indication of the disease,as many tumors are asymptomatic in their early stages.Studies have shown that 40.3%of cases involve the macular region,which explains why ocular symptoms are often the first manifestation of the disease[2].When choroidal metastasis is suspected in patients without a history of cancer,a combination of diagnostic tools should be used to identify the primary source of the tumor.Choroidal tumors can serve as an indication of future lung cancer diagnosis in some patients with lung cancer[1].In this report,we present a case of bilateral lung adenocarcinoma where ocular symptoms were the first indication of the disease.
