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 I...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.展开更多
Background：Pyroptosis is the term for caspase-l-dependent cell death associated with pro-inflammatory cytokines.The role of alveolar macrophage （AM） pyroptosis in the pathogenesis of the acute lung injury and acute...Background：Pyroptosis is the term for caspase-l-dependent cell death associated with pro-inflammatory cytokines.The role of alveolar macrophage （AM） pyroptosis in the pathogenesis of the acute lung injury and acute respiratory distress syndrome （ALI/ARDS） remains unclear.Methods：C57BL/6 wild-type mice were assigned to sham,lipopolysaccharide （LPS） ＋ vehicle,LPS ＋ acetyl-tyrosyl-valyl-alanyl-aspartyl-chloromethylketone （Ac-YVAD-CMK） and LPS ＋ Z-Asp-Glu-Val-Asp-fluoromethylketone groups.Mice were given intraperitoneal （IP） injections of LPS.Drugs were IP injected 1 h before LPS administration.Mice were sacrificed 16 h after LPS administration,and AMs were isolated.Western blot analysis for active caspase-1 and cleaved caspase-3,evaluation of lung injury and a cytokine release analysis were performed.AMs were treated with LPS and adenosine triphosphate （ATP）;caspase-l-dependent cell death was evaluated using flow cytometry;the apoptosis-associated speck-like protein containing a caspase recruitment domain （ASC） pyroptosomes were examined by immunofluorescence.Results：The expression of activated caspase-1 in AMs was enhanced following LPS challenge compared with the sham group.In the ex vivo study,the caspase-1/propidium iodide-positive cells,caspase-1 specks and ASC pyroptosomes were up-regulated in AMs following LPS/ATP stimulation.The specific caspase-1 inhibitor Ac-YVAD-CMK inhibited the activation of caspase-1 and pyroptotic cell death.Ac-YVAD-CMK also reduced the lung injury,pulmonary edema and total protein in bronchoalveolar lavage fluid （BALF）.In addition,Ac-YVAD-CMK significantly inhibited interleukin-β （IL-lβ） release both in serum and BALF and reduced the levels of IL-18,tumor necrosis factor-α （TNF-α）,High Mobility Group Box 1 （HMGB1） in BALF during LPS-induced ALI/ARDS.Conclusions：This study reported AM pyroptosis during LPS-induced ALI/ARDS in mice and has demonstrated that Ac-YVAD-CMK can prevent AM-induced pyroptosis and lung injury.These preliminary findings may form the basis for further studies to evaluate this pathway as a target for prevention or reduction of ALI/ARDS.展开更多
Severe acute pancreatitis-associated acute lung injury(SAP-ALI) is a serious disease associated with high mortality. Emodin has been applied to alleviate SAP-ALI;however, the mechanism remains unclear. We report that ...Severe acute pancreatitis-associated acute lung injury(SAP-ALI) is a serious disease associated with high mortality. Emodin has been applied to alleviate SAP-ALI;however, the mechanism remains unclear. We report that the therapeutic role of emodin in attenuating SAP-ALI is partly dependent on an exosomal mechanism. SAP rats had increased levels of plasma exosomes with altered protein contents compared to the sham rats. These infused plasma exosomes tended to accumulate in the lungs and promoted the hyper-activation of alveolar macrophages and inflammatory damage. Conversely,emodin treatment decreased the plasma/pancreatic exosome levels in the SAP rats. Emodin-primed exosomes showed less pro-inflammatory effects in alveolar macrophages and lung tissues than SAP exosomes. In detail, emodin-primed exosomes suppressed the NF-κB pathway to reduce the activation of alveolar macrophage and ameliorate lung inflammation by regulating PPARγ pathway, while these effects were amplified/abolished by PPARγ agonist/antagonist. Blockage of pancreatic acinar cell exosome biogenesis also exhibited suppression of alveolar macrophage activation and reduction of lung inflammation. This study suggests a vital role of exosomes in participating inflammation-associated organ-injury,and indicates emodin can attenuate SAP-ALI by reducing the pancreatic exosome-mediated alveolar macrophage activation.展开更多
Objective: To determine the role of mononuclear macrophages in the pathogenesis of acute lung injury during acute obstructive cholangitis. Methods: Sixty Wistar rats were used to study the correlation between the beha...Objective: To determine the role of mononuclear macrophages in the pathogenesis of acute lung injury during acute obstructive cholangitis. Methods: Sixty Wistar rats were used to study the correlation between the behavior of mononuclear macrophages and acute pulmonary injury during a- cute obstructive cholangitis (AOC). Animal model of AOC was made according to the method that the common bile duct was injected with Escherichia coli and ligated. The rats were killed at 6 h, 12 h, 24 h and 48 h after operation. The phagocytic function of Kupffer cells (KCs), the number of alveolar macro- phages (AMs) in bronchoalveolar lavage liquid, and the extravascular water content of lung tissue were measured. The levels of lipid peroxide (LPO) and supperoxide dismutase (SOD) were determined too. Pathological alterations of liver and lung tissue were observed under light and electron microscopes. Results: KCs phagocytic function was significantly el- evated at the 6th hour but markedly decreased from the 24th hour to the 48th hour in the AOC group as compared with the control (P<0. 05). From the 12th to the 48th hour, the number of AMs, the ex- travascular water content of lung tissue, and the con- tent of LPO significantly increased, but the SOD lev- el of lung tissue decreased greatly (P<0. 05). Mor- phologically, KCs proliferated diffusely in the early period in livers of the AOC group, but decreased markedly in the late period. Mitochondria of KCs were swollen or even vacuolated; focal cytoplasmic degeneration and many myeli like figures could be seen in the cytoplasm. The changes of injury such as disturbance of pulmonary capillary blood circula- tion, degeneration and/or necrosis of the lung tissue and endothelium, and inflammatory reactions could be observed. In other two groups, no evident mor- phological changes were observed. Conclusions: KCs phagocytic function is decreased, whereas AM is activated by the invading bacteria to release such inflammatory mediators as free radicals, resulting in acute pulmonary injury. It seems that there is a close relationship between the functional status of mononuclear macrophages and the develop- ment of acute lung injury. The dysfunction of mono- nuclear macrophages may play an important role in the pathogenesis of multiple organ damage, especial- ly acute pulmonary injury.展开更多
OBJECTIVE:To establish an in vitro model of radiation-induced lung injury using rat lung alveolar macrophages(NR8383).METHODS:Using a medical electronic linear accelerator,cells were irradiated with either 0 Gy or 6 G...OBJECTIVE:To establish an in vitro model of radiation-induced lung injury using rat lung alveolar macrophages(NR8383).METHODS:Using a medical electronic linear accelerator,cells were irradiated with either 0 Gy or 6 Gy X-rays.At 6,12,24,30 and 48 h,the DNA damage index(8-OHd G)and lipid damage index(MDA)were measured in the two groups.We also determined the levels of tumor necrosis factor-alpha(TNF-α),interleukin-6(IL-6)and transforming growth factor-β(TGF-β).RESULTS:The levels of 8-OHd G and MDA in the 6 Gy irradiation group were higher than those in the0 Gy group at 6,12,24,30 and 48 h after irradiation.The levels reached the highest value-6 h after irradiation,and then gradually decreased.The levels of the inflammatory factors TNF-α,TGF-βand IL-6 were higher in the 6 Gy irradiation group than those in the 0 Gy group at 6,12,24,30 and 48 h after irradiation.CONCLUSION:Six Gy X-ray irradiated NR8383 cells can be used to establish an in-vitro model of radiation-induced lung injury.The levels of 8-OHd G,MDA,TNF-α,TGF-βand IL-6 can be used as effective evaluation indicators.展开更多
This study investigated the effects of hyperoxia on dynamic changes of thioredoxin-1 （Trx1） and thioredoxin reductase-1 （TrxR1） in alveolar type Ⅱ epithelial cells （AECⅡ） of premature rats. Pregnant Sprague-Da...This study investigated the effects of hyperoxia on dynamic changes of thioredoxin-1 （Trx1） and thioredoxin reductase-1 （TrxR1） in alveolar type Ⅱ epithelial cells （AECⅡ） of premature rats. Pregnant Sprague-Dawley rats were sacrificed on day 19 of gestation. AECⅡ were isolated and purified from the lungs of premature rats. When cultured to 80% confluence, in vitro cells were randomly divided into air group and hyperoxia group. Cells in the hyperoxia group were continuously exposed to 95% O2/5% CO2 and those in the air group to 95% air/5% CO2. After 12, 24 and 48 h, cells in the two groups were harvested to detect their reactive oxygen species （ROS）, apoptosis, TrxR1 activity and the expressions of Trx1 and TrxR1 by corresponding protocols, respectively. The results showed that AECⅡ exposed to hyperoxia generated excessive ROS and the apoptosis percentage in the hyperoxia group was increased significantly at each time points as compared with that in the air group （P0.001）. Moreover, TrxR1 activity was found to be markedly depressed in the hyperoxia group in comparison to that in the air group （P0.001）. RT-PCR showed the expressions of both Trx1 and TrxR1 mRNA were significantly increased in AECⅡ exposed to hyperoxia for 12 and 24 h （P0.01）, respectively. At 48 h, the level of Trx1 mRNA as well as that of TrxR1 mRNA in the hyperoxia group was reduced and showed no significant difference from that in the air group （P0.05）. Western blotting showed the changes of Trx1 protein expressions in the hyperoxia group paralleled those of Trx1 mRNA expressions revealed by RT-PCR. It was concluded that hyperoxia can up-regulate the protective Trx1/TrxR1 expressed by AECⅡ in a certain period, however, also cause dysfunction of the cytoplasmic thioredoxin system by decreasing TrxR1 activity, which may contribute to the progression of oxidative stress and cell apoptosis and finally result in lung injury.展开更多
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 ...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.展开更多
Objective:To describe the clinical features,proportion of lipid-laden alveolar macrophages in bronchoalveolar lavage(BAL),and short-term and 6-month to 12-month outcomes of patients with Electronic cigarette/Vaping pr...Objective:To describe the clinical features,proportion of lipid-laden alveolar macrophages in bronchoalveolar lavage(BAL),and short-term and 6-month to 12-month outcomes of patients with Electronic cigarette/Vaping product use-Associated Lung Injury(EVALI).Methods:Retrospective review of clinical characteristics,radiographs,and BAL samples for all patients with a history of vaping who presented with acute hypoxemic respiratory failure to the University Hospital in San Antonio,Texas from 9/2019 to 6/2020 was performed.Results:We report 16 cases(15 men;median age,30 years[range 19-75])of EVALI with a history of vaping Tetrahydrocannabinol(THC),nicotine,or both.The most common presenting symptoms were tachycardia,dyspnea,cough,and fever.All patients required supplemental oxygen,including two who required noninvasive positive pressure ventilation,and five who required mechanical ventilation.All 16 patients had bilateral ground-glass opacities(GGO)with peripheral sparing on chest computerized tomography(CT).Cultures were negative,except for one patient who tested positive for rhinovirus.COVID-19 PCR was done in one individual which was negative.Cytology demonstrated lipid-laden macrophages on Oil-Red-O stain on fresh(i.e.,without fixative)BAL in the majority of patients(N=12)with a mean lipid-saturation percentage of 78%[range,44%-100%]and the mean Colombo count of 194[range,101-359].Fifteen patients were treated with systemic corticosteroids.The median length of hospital stay was 10 days.At discharge,three patients required supplemental oxygen.Eight of those who had follow-up imaging showed resolution of GGO.One patient had a relapse of symptoms and was again treated with systemic corticosteroids and mycophenolate,with resolution of symptoms.Fourteen patients who were evaluated after discharge denied vaping post-discharge(two patients were not able to be contacted and did not keep follow-up appointments).Conclusions:Successful diagnosis and management of EVALI requires a high clinical suspicion,thorough evaluation to rule out infectious etiologies,and aggressive treatment with systemic corticosteroids,along with sustained abstinence from vaping.展开更多
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 specifici...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.展开更多
基金supported by the National Natural Science Foundation of China(No.82104581,No.82060864).
文摘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.
基金The author thanks the National Natural Science Foundation of China （No. 81470266）.
文摘Background：Pyroptosis is the term for caspase-l-dependent cell death associated with pro-inflammatory cytokines.The role of alveolar macrophage （AM） pyroptosis in the pathogenesis of the acute lung injury and acute respiratory distress syndrome （ALI/ARDS） remains unclear.Methods：C57BL/6 wild-type mice were assigned to sham,lipopolysaccharide （LPS） ＋ vehicle,LPS ＋ acetyl-tyrosyl-valyl-alanyl-aspartyl-chloromethylketone （Ac-YVAD-CMK） and LPS ＋ Z-Asp-Glu-Val-Asp-fluoromethylketone groups.Mice were given intraperitoneal （IP） injections of LPS.Drugs were IP injected 1 h before LPS administration.Mice were sacrificed 16 h after LPS administration,and AMs were isolated.Western blot analysis for active caspase-1 and cleaved caspase-3,evaluation of lung injury and a cytokine release analysis were performed.AMs were treated with LPS and adenosine triphosphate （ATP）;caspase-l-dependent cell death was evaluated using flow cytometry;the apoptosis-associated speck-like protein containing a caspase recruitment domain （ASC） pyroptosomes were examined by immunofluorescence.Results：The expression of activated caspase-1 in AMs was enhanced following LPS challenge compared with the sham group.In the ex vivo study,the caspase-1/propidium iodide-positive cells,caspase-1 specks and ASC pyroptosomes were up-regulated in AMs following LPS/ATP stimulation.The specific caspase-1 inhibitor Ac-YVAD-CMK inhibited the activation of caspase-1 and pyroptotic cell death.Ac-YVAD-CMK also reduced the lung injury,pulmonary edema and total protein in bronchoalveolar lavage fluid （BALF）.In addition,Ac-YVAD-CMK significantly inhibited interleukin-β （IL-lβ） release both in serum and BALF and reduced the levels of IL-18,tumor necrosis factor-α （TNF-α）,High Mobility Group Box 1 （HMGB1） in BALF during LPS-induced ALI/ARDS.Conclusions：This study reported AM pyroptosis during LPS-induced ALI/ARDS in mice and has demonstrated that Ac-YVAD-CMK can prevent AM-induced pyroptosis and lung injury.These preliminary findings may form the basis for further studies to evaluate this pathway as a target for prevention or reduction of ALI/ARDS.
基金supported by Natural Science Foundation of China(Nos.81974552,81774160)Technology Agency of Sichuan Province Foundation Project(No.2019YFS0389)Scientific Research Foundation of the Science and Technology Department of Sichuan Province(No.2022YFS0417,China).
文摘Severe acute pancreatitis-associated acute lung injury(SAP-ALI) is a serious disease associated with high mortality. Emodin has been applied to alleviate SAP-ALI;however, the mechanism remains unclear. We report that the therapeutic role of emodin in attenuating SAP-ALI is partly dependent on an exosomal mechanism. SAP rats had increased levels of plasma exosomes with altered protein contents compared to the sham rats. These infused plasma exosomes tended to accumulate in the lungs and promoted the hyper-activation of alveolar macrophages and inflammatory damage. Conversely,emodin treatment decreased the plasma/pancreatic exosome levels in the SAP rats. Emodin-primed exosomes showed less pro-inflammatory effects in alveolar macrophages and lung tissues than SAP exosomes. In detail, emodin-primed exosomes suppressed the NF-κB pathway to reduce the activation of alveolar macrophage and ameliorate lung inflammation by regulating PPARγ pathway, while these effects were amplified/abolished by PPARγ agonist/antagonist. Blockage of pancreatic acinar cell exosome biogenesis also exhibited suppression of alveolar macrophage activation and reduction of lung inflammation. This study suggests a vital role of exosomes in participating inflammation-associated organ-injury,and indicates emodin can attenuate SAP-ALI by reducing the pancreatic exosome-mediated alveolar macrophage activation.
基金This study was supported by the National Natural Science Foundation of China (No. 39970719, 30170919).
文摘Objective: To determine the role of mononuclear macrophages in the pathogenesis of acute lung injury during acute obstructive cholangitis. Methods: Sixty Wistar rats were used to study the correlation between the behavior of mononuclear macrophages and acute pulmonary injury during a- cute obstructive cholangitis (AOC). Animal model of AOC was made according to the method that the common bile duct was injected with Escherichia coli and ligated. The rats were killed at 6 h, 12 h, 24 h and 48 h after operation. The phagocytic function of Kupffer cells (KCs), the number of alveolar macro- phages (AMs) in bronchoalveolar lavage liquid, and the extravascular water content of lung tissue were measured. The levels of lipid peroxide (LPO) and supperoxide dismutase (SOD) were determined too. Pathological alterations of liver and lung tissue were observed under light and electron microscopes. Results: KCs phagocytic function was significantly el- evated at the 6th hour but markedly decreased from the 24th hour to the 48th hour in the AOC group as compared with the control (P<0. 05). From the 12th to the 48th hour, the number of AMs, the ex- travascular water content of lung tissue, and the con- tent of LPO significantly increased, but the SOD lev- el of lung tissue decreased greatly (P<0. 05). Mor- phologically, KCs proliferated diffusely in the early period in livers of the AOC group, but decreased markedly in the late period. Mitochondria of KCs were swollen or even vacuolated; focal cytoplasmic degeneration and many myeli like figures could be seen in the cytoplasm. The changes of injury such as disturbance of pulmonary capillary blood circula- tion, degeneration and/or necrosis of the lung tissue and endothelium, and inflammatory reactions could be observed. In other two groups, no evident mor- phological changes were observed. Conclusions: KCs phagocytic function is decreased, whereas AM is activated by the invading bacteria to release such inflammatory mediators as free radicals, resulting in acute pulmonary injury. It seems that there is a close relationship between the functional status of mononuclear macrophages and the develop- ment of acute lung injury. The dysfunction of mono- nuclear macrophages may play an important role in the pathogenesis of multiple organ damage, especial- ly acute pulmonary injury.
基金Supported by the National Natural Science Foundation of China the Mechanism Underlying Nourishing Yin,Clearing Lung and Activating Blood Circulation to Regulate AMPK Mediated Autophagy in Radiation-induced Lung Injury(No.81673754)。
文摘OBJECTIVE:To establish an in vitro model of radiation-induced lung injury using rat lung alveolar macrophages(NR8383).METHODS:Using a medical electronic linear accelerator,cells were irradiated with either 0 Gy or 6 Gy X-rays.At 6,12,24,30 and 48 h,the DNA damage index(8-OHd G)and lipid damage index(MDA)were measured in the two groups.We also determined the levels of tumor necrosis factor-alpha(TNF-α),interleukin-6(IL-6)and transforming growth factor-β(TGF-β).RESULTS:The levels of 8-OHd G and MDA in the 6 Gy irradiation group were higher than those in the0 Gy group at 6,12,24,30 and 48 h after irradiation.The levels reached the highest value-6 h after irradiation,and then gradually decreased.The levels of the inflammatory factors TNF-α,TGF-βand IL-6 were higher in the 6 Gy irradiation group than those in the 0 Gy group at 6,12,24,30 and 48 h after irradiation.CONCLUSION:Six Gy X-ray irradiated NR8383 cells can be used to establish an in-vitro model of radiation-induced lung injury.The levels of 8-OHd G,MDA,TNF-α,TGF-βand IL-6 can be used as effective evaluation indicators.
基金supported by a grant from the National Natural Sciences Foundation of China (No. 30770944)
文摘This study investigated the effects of hyperoxia on dynamic changes of thioredoxin-1 （Trx1） and thioredoxin reductase-1 （TrxR1） in alveolar type Ⅱ epithelial cells （AECⅡ） of premature rats. Pregnant Sprague-Dawley rats were sacrificed on day 19 of gestation. AECⅡ were isolated and purified from the lungs of premature rats. When cultured to 80% confluence, in vitro cells were randomly divided into air group and hyperoxia group. Cells in the hyperoxia group were continuously exposed to 95% O2/5% CO2 and those in the air group to 95% air/5% CO2. After 12, 24 and 48 h, cells in the two groups were harvested to detect their reactive oxygen species （ROS）, apoptosis, TrxR1 activity and the expressions of Trx1 and TrxR1 by corresponding protocols, respectively. The results showed that AECⅡ exposed to hyperoxia generated excessive ROS and the apoptosis percentage in the hyperoxia group was increased significantly at each time points as compared with that in the air group （P0.001）. Moreover, TrxR1 activity was found to be markedly depressed in the hyperoxia group in comparison to that in the air group （P0.001）. RT-PCR showed the expressions of both Trx1 and TrxR1 mRNA were significantly increased in AECⅡ exposed to hyperoxia for 12 and 24 h （P0.01）, respectively. At 48 h, the level of Trx1 mRNA as well as that of TrxR1 mRNA in the hyperoxia group was reduced and showed no significant difference from that in the air group （P0.05）. Western blotting showed the changes of Trx1 protein expressions in the hyperoxia group paralleled those of Trx1 mRNA expressions revealed by RT-PCR. It was concluded that hyperoxia can up-regulate the protective Trx1/TrxR1 expressed by AECⅡ in a certain period, however, also cause dysfunction of the cytoplasmic thioredoxin system by decreasing TrxR1 activity, which may contribute to the progression of oxidative stress and cell apoptosis and finally result in lung injury.
基金supported by National Natural Science Foundation of China(No.81960351)High-level Talent Fund of Hainan Province(No.822RC835).
文摘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.
文摘Objective:To describe the clinical features,proportion of lipid-laden alveolar macrophages in bronchoalveolar lavage(BAL),and short-term and 6-month to 12-month outcomes of patients with Electronic cigarette/Vaping product use-Associated Lung Injury(EVALI).Methods:Retrospective review of clinical characteristics,radiographs,and BAL samples for all patients with a history of vaping who presented with acute hypoxemic respiratory failure to the University Hospital in San Antonio,Texas from 9/2019 to 6/2020 was performed.Results:We report 16 cases(15 men;median age,30 years[range 19-75])of EVALI with a history of vaping Tetrahydrocannabinol(THC),nicotine,or both.The most common presenting symptoms were tachycardia,dyspnea,cough,and fever.All patients required supplemental oxygen,including two who required noninvasive positive pressure ventilation,and five who required mechanical ventilation.All 16 patients had bilateral ground-glass opacities(GGO)with peripheral sparing on chest computerized tomography(CT).Cultures were negative,except for one patient who tested positive for rhinovirus.COVID-19 PCR was done in one individual which was negative.Cytology demonstrated lipid-laden macrophages on Oil-Red-O stain on fresh(i.e.,without fixative)BAL in the majority of patients(N=12)with a mean lipid-saturation percentage of 78%[range,44%-100%]and the mean Colombo count of 194[range,101-359].Fifteen patients were treated with systemic corticosteroids.The median length of hospital stay was 10 days.At discharge,three patients required supplemental oxygen.Eight of those who had follow-up imaging showed resolution of GGO.One patient had a relapse of symptoms and was again treated with systemic corticosteroids and mycophenolate,with resolution of symptoms.Fourteen patients who were evaluated after discharge denied vaping post-discharge(two patients were not able to be contacted and did not keep follow-up appointments).Conclusions:Successful diagnosis and management of EVALI requires a high clinical suspicion,thorough evaluation to rule out infectious etiologies,and aggressive treatment with systemic corticosteroids,along with sustained abstinence from vaping.
基金This work is supported by the Field of Scientific Research Develop Project of North Sichuan Medical College in 2017(No.CBY17-A-YB39)the Science and Technology Project of the Health Planning Committee of Sichuan(No.18PJ430).
文摘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.
