1.Effect of Isodon ternifolius-medicated serum on hepatic stellate cells based on TLR4/NF-κB/NLRP3 signaling pathway.
Gui-Dong HUANG ; Zhi-Pin ZHOU ; Zhi PANG ; Le QIN ; Rui-Sheng WU ; Yong CHEN ; Xiao-Xue YE
China Journal of Chinese Materia Medica 2023;48(14):3913-3921
The present study aimed to investigate the inhibitory effect and mechanism of Isodon terricolous-medicated serum on lipopolysaccharide(LPS)-induced hepatic stellate cell(HSC) activation. LPS-induced HSCs were divided into a blank control group, an LPS model group, a colchicine-medicated serum group, an LPS + blank serum group, an I. terricolous-medicated serum group, a Toll-like receptor 4(TLR4) blocker group, and a TLR4 blocker + I. terricolous-medicated serum group. HSC proliferation was detected by methyl thiazolyl tetrazolium(MTT) assay. Enzyme-linked immunosorbent assay(ELISA) was used to measure type Ⅰ collagen(COL Ⅰ), COL Ⅲ, transforming growth factor-β1(TGF-β1), intercellular adhesion molecule-1(ICAM-1), α-smooth muscle actin(α-SMA), vascular cell adhesion molecule-1(VCAM-1), cysteinyl aspartate-specific proteinase-1(caspase-1), and monocyte chemotactic protein-1(MCP-1). Real-time PCR(RT-PCR) was used to detect mRNA expression of TLR4, IκBα, and NOD-like receptor thermal protein domain associated protein 3(NLRP3), nuclear factor-κB(NF-κB) p65, gasdermin D(GSDMD), and apoptosis-associated speck-like protein containing a CARD(ASC) in HSCs. Western blot(WB) was used to detect the protein levels of TLR4, p-IκBα, NF-κB p65, NLRP3, ASC, and GSDMD in HSCs. The results showed that I. terricolous-medicated serum could inhibit the proliferation activity of HSCs and inhibit the secretion of COL Ⅰ, COL Ⅲ, α-SMA, TGF-β1, caspase-1, MCP-1, VCAM-1, and ICAM-1 in HSCs. Compared with the LPS model group, the I. terricolous-medicated serum group, the colchicine-medicated serum group, and the TLR4 blocker group showed down-regulated expression of p-IκBα, NLRP3, NF-κB p65, GSDMD, and ASC, and up-regulated expression of IκBα. Compared with the TLR4 blocker group, the TLR4 blocker + I. terricolous-medicated serum group showed decreased expression of TLR4, p-IκBα, NLRP3, NF-κB p65, GSDMD, and ASC, and increased expression of IκBα. In conclusion, I. terricolous-medicated serum down-regulates HSC activation by inhibiting the TLR4/NF-κB/NLRP3 signaling pathway.
NF-kappa B/metabolism*
;
Hepatic Stellate Cells
;
Transforming Growth Factor beta1/metabolism*
;
NF-KappaB Inhibitor alpha/metabolism*
;
Intercellular Adhesion Molecule-1/metabolism*
;
Isodon
;
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism*
;
Toll-Like Receptor 4/metabolism*
;
Vascular Cell Adhesion Molecule-1/metabolism*
;
Lipopolysaccharides/pharmacology*
;
Signal Transduction
;
Colchicine/pharmacology*
;
Caspases
2.Two cases of airway dysfunction related to diacetyl exposure.
Bo Hua HU ; Xiao Ping HUANG ; Xiao Pin YU ; Li Na CHEN ; Lu Yan DAI ; Guo Chuan MAO
Chinese Journal of Industrial Hygiene and Occupational Diseases 2023;41(3):222-224
Occupational exposure to diacetyl can lead to bronchiolitis obliterans. In this paper, two patients with severe obstructive ventilation disorder who were exposed to diacetyl at a fragrance and flavours factory were analyzed. The clinical manifestations were cough and shortness of breath. One of them showed Mosaic shadows and uneven perfusion in both lungs on CT, while the other was normal. Field investigation found that 4 of the 8 workers in the factory were found to have obstructive ventilation disorder, and 2 had small airway dysfunction. This paper summarizes the diagnostic process of patients in order to improve the understanding of airway dysfunction caused by occupational exposure to diacetyl and promote the development of relevant standards.
Humans
;
Diacetyl/adverse effects*
;
Occupational Diseases/diagnosis*
;
Occupational Exposure/adverse effects*
;
Lung
;
Bronchiolitis Obliterans/diagnosis*
3.A Case Series of Olfactory Dysfunction in Imported COVID-19 Patients: A 12-Month Follow-Up Study.
Ni WANG ; Ming Bo YANG ; Pu Ye YANG ; Ren Bo CHEN ; Fei HUANG ; Nan Nan SHI ; Yan MA ; Yan ZHANG ; You XU ; Si Hong LIU ; Heng Yi LU ; Qing Qing FU ; Yi Pin FAN ; Hong Min KAN ; Xiao Hong WANG ; Ya Ling GUO
Biomedical and Environmental Sciences 2022;35(5):402-411
Objective:
The scientific community knows little about the long-term influence of coronavirus disease 2019 (COVID-19) on olfactory dysfunction (OD). With the COVID-19 pandemic ongoing worldwide, the risk of imported cases remains high. In China, it is necessary to understand OD in imported cases.
Methods:
A prospective follow-up design was adopted. A total of 11 self-reported patients with COVID-19 and OD from Xi'an No. 8 Hospital were followed between August 19, 2021, and December 12, 2021. Demographics, clinical characteristics, laboratory and radiological findings, and treatment outcomes were analyzed at admission. We surveyed the patients via telephone for recurrence and sequelae at the 1-, 6-, and 12-month follow-up.
Results:
Eleven patients with OD were enrolled; of these, 54.5% (6/11) had hyposmia and 45.5% (5/11) had anosmia. 63.6% (7/11) reported OD before or on the day of admission as their initial symptom; of these, 42.9% (3/7) described OD as the only symptom. All patients in the study received combined treatment with traditional Chinese medicine and Western medicine, and 72.7% (8/11) had partially or fully recovered at discharge. In terms of OD recovery at the 12-month follow-up, 45.5% (5/11) reported at least one sequela, 81.8% (9/11) had recovered completely, 18.2% (2/11) had recovered partially, and there were no recurrent cases.
Conclusions
Our data revealed that OD frequently presented as the initial or even the only symptom among imported cases. Most OD improvements occurred in the first 2 weeks after onset, and patients with COVID-19 and OD had favorable treatment outcomes during long-term follow-up. A better understanding of the pathogenesis and appropriate treatment of OD is needed to guide clinicians in the care of these patients.
COVID-19/complications*
;
Follow-Up Studies
;
Humans
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Olfaction Disorders/etiology*
;
Pandemics
;
Prospective Studies
;
SARS-CoV-2
4.Relationship between body mass index and sexual development in Chinese children.
Xiao Qin XU ; Jian Wei ZHANG ; Rui Min CHEN ; Jing Si LUO ; Shao Ke CHEN ; Rong Xiu ZHENG ; Di WU ; Min ZHU ; Chun Lin WANG ; Yan LIANG ; Hui YAO ; Hai Yan WEI ; Zhe SU ; Mireguli MAIMAITI ; Hong Wei DU ; Fei Hong LUO ; Pin LI ; Shu Ting SI ; Wei WU ; Ke HUANG ; Guan Ping DONG ; Yun Xian YU ; Jun Fen FU
Chinese Journal of Pediatrics 2022;60(4):311-316
Objective: To investigate the relationship between body mass index (BMI) and sexual development in Chinese children. Methods: A nationwide multicenter and population-based large cross-sectional study was conducted in 13 provinces, autonomous regions and municipalities of China from January 2017 to December 2018. Data on sex, age, height, weight were collected, BMI was calculated and sexual characteristics were analyzed. The subjects were divided into four groups based on age, including ages 3-<6 years, 6-<10 years, 10-<15 years and 15-<18 years. Multiple Logistic regression models were used for evaluating the associations of BMI with sexual development in children. Dichotomous Logistic regression was used to compare the differences in the distribution of early and non-early puberty among normal weight, overweight and obese groups. Curves were drawn to analyze the relationship between the percentage of early puberty and BMI distribution in girls and boys at different Tanner stages. Results: A total of 208 179 healthy children (96 471 girls and 111 708 boys) were enrolled in this study. The OR values of B2, B3 and B4+ in overweight girls were 1.72 (95%CI: 1.56-1.89), 3.19 (95%CI: 2.86-3.57), 7.14 (95%CI: 6.33-8.05) and in obese girls were 2.05 (95%CI: 1.88-2.24), 4.98 (95%CI: 4.49-5.53), 11.21 (95%CI: 9.98-12.59), respectively; while the OR values of G2, G3, G4+ in overweight boys were 1.27 (95%CI: 1.17-1.38), 1.52 (95%CI: 1.36-1.70), 1.88 (95%CI: 1.66-2.14) and in obese boys were 1.27 (95%CI: 1.17-1.37), 1.59 (95%CI: 1.43-1.78), and 1.93 (95%CI: 1.70-2.18) (compared with normal weight Tanner 1 group,all P<0.01). Analysis in different age groups found that OR values of obese girls at B2 stage and boys at G2 stage were 2.02 (95%CI: 1.06-3.86) and 2.32 (95%CI:1.05-5.12) in preschool children aged 3-<6 years, respectively (both P<0.05). And in the age group of 6-10 years, overweight girls had a 5.45-fold risk and obese girls had a 12.54-fold risk of B3 stage compared to girls with normal BMI. Compared with normal weight children, the risk of early puberty was 2.67 times higher in overweight girls, 3.63 times higher in obese girls, and 1.22 times higher in overweight boys, 1.35 times higher in obese boys (all P<0.01). Among the children at each Tanner stages, the percentage of early puberty increased with the increase of BMI, from 5.7% (80/1 397), 16.1% (48/299), 13.8% (27/195) to 25.7% (198/769), 65.1% (209/321), 65.4% (157/240) in girls aged 8-<9, 10-<11 and 11-<12 years, and 6.6% (34/513), 18.7% (51/273), 21.6% (57/264) to 13.3% (96/722), 46.4% (140/302), 47.5% (105/221) in boys aged 9-<10, 12-<13 and 13-<14 years, respectively. Conclusions: BMI is positively correlated with sexual development in both Chinese boys and girls, and the correlation is stronger in girls. Obesity is a risk factor for precocious puberty in preschool children aged 3-<6 years, and 6-<10 years of age is a high risk period for early development in obese girls.
Adolescent
;
Body Mass Index
;
Child
;
Child, Preschool
;
China/epidemiology*
;
Cross-Sectional Studies
;
Female
;
Humans
;
Male
;
Obesity/epidemiology*
;
Overweight/epidemiology*
;
Puberty
;
Puberty, Precocious
;
Sexual Development
5.Non-alcoholic fatty liver disease increases risk of carotid atherosclerosis and ischemic stroke: An updated meta-analysis with 135,602 individuals
Ansel Shao Pin TANG ; Kai En CHAN ; Jingxuan QUEK ; Jieling XIAO ; Phoebe TAY ; Margaret TENG ; Keng Siang LEE ; Snow Yunni LIN ; May Zin MYINT ; Benjamin TAN ; Vijay K SHARMA ; Darren Jun Hao TAN ; Wen Hui LIM ; Apichat KAEWDECH ; Daniel HUANG ; Nicholas WS CHEW ; Mohammad Shadab SIDDIQUI ; Arun J SANYAL ; Mark MUTHIAH ; Cheng Han NG
Clinical and Molecular Hepatology 2022;28(3):483-496
Background/Aims:
Non-alcoholic fatty liver disease (NAFLD) is associated with the development of cardiovascular disease. While existing studies have examined cardiac remodeling in NAFLD, there has been less emphasis on the development of carotid atherosclerosis and stroke. We sought to conduct a meta-analysis to quantify the prevalence, risk factors, and degree of risk increment of carotid atherosclerosis and stroke in NAFLD.
Methods:
Embase and Medline were searched for articles relating to NAFLD, carotid atherosclerosis, and stroke. Proportional data was analysed using a generalized linear mixed model. Pairwise meta-analysis was conducted to obtain odds ratio or weighted mean difference for comparison between patients with and without NAFLD.
Results:
From pooled analysis of 30 studies involving 7,951 patients with NAFLD, 35.02% (95% confidence interval [CI], 27.36–43.53%) had carotid atherosclerosis with an odds ratio of 3.20 (95% CI, 2.37–4.32; P<0.0001). Pooled analysis of 25,839 patients with NAFLD found the prevalence of stroke to be 5.04% (95% CI, 2.74–9.09%) with an odds ratio of 1.88 (95% CI, 1.23–2.88; P=0.02) compared to non-NAFLD. The degree of steatosis assessed by ultrasonography in NAFLD was closely associated with risk of carotid atherosclerosis and stroke. Older age significantly increased the risk of developing carotid atherosclerosis, but not stroke in NAFLD.
Conclusions
This meta-analysis shows that a stepwise increment of steatosis of NAFLD can significantly increase the risk of carotid atherosclerosis and stroke development in NAFLD. Patients more than a third sufferred from carotid atherosclerosis and routine assessment of carotid atherosclerosis is quintessential in NAFLD.
6.Association of Overlapped and Un-overlapped Comorbidities with COVID-19 Severity and Treatment Outcomes: A Retrospective Cohort Study from Nine Provinces in China.
Yan MA ; Dong Shan ZHU ; Ren Bo CHEN ; Nan Nan SHI ; Si Hong LIU ; Yi Pin FAN ; Gui Hui WU ; Pu Ye YANG ; Jiang Feng BAI ; Hong CHEN ; Li Ying CHEN ; Qiao FENG ; Tuan Mao GUO ; Yong HOU ; Gui Fen HU ; Xiao Mei HU ; Yun Hong HU ; Jin HUANG ; Qiu Hua HUANG ; Shao Zhen HUANG ; Liang JI ; Hai Hao JIN ; Xiao LEI ; Chun Yan LI ; Min Qing LI ; Qun Tang LI ; Xian Yong LI ; Hong De LIU ; Jin Ping LIU ; Zhang LIU ; Yu Ting MA ; Ya MAO ; Liu Fen MO ; Hui NA ; Jing Wei WANG ; Fang Li SONG ; Sheng SUN ; Dong Ting WANG ; Ming Xuan WANG ; Xiao Yan WANG ; Yin Zhen WANG ; Yu Dong WANG ; Wei WU ; Lan Ping WU ; Yan Hua XIAO ; Hai Jun XIE ; Hong Ming XU ; Shou Fang XU ; Rui Xia XUE ; Chun YANG ; Kai Jun YANG ; Sheng Li YUAN ; Gong Qi ZHANG ; Jin Bo ZHANG ; Lin Song ZHANG ; Shu Sen ZHAO ; Wan Ying ZHAO ; Kai ZHENG ; Ying Chun ZHOU ; Jun Teng ZHU ; Tian Qing ZHU ; Hua Min ZHANG ; Yan Ping WANG ; Yong Yan WANG
Biomedical and Environmental Sciences 2020;33(12):893-905
Objective:
Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear.
Methods:
A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio (
Results:
Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks.
Conclusion
Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult
;
Aged
;
COVID-19/virology*
;
China/epidemiology*
;
Comorbidity
;
Female
;
Humans
;
Male
;
Middle Aged
;
Retrospective Studies
;
Severity of Illness Index
;
Treatment Outcome
7.Relationship between social norms and smoking cessation among male smokers in three cities of China
Xin-yuan HUANG ; Wen-jie FU ; Jing WANG ; Hong LI ; Hai-ying ZHANG ; Xiao-xia LI ; Yong YANG ; Pin-pin ZHENG
Shanghai Journal of Preventive Medicine 2020;32(2):102-
Objective To explore the relationship between social norms and smoking intention, among male smokers in China. Methods A total 3 621 (with 95.8% of effective response rate) male smokers were selected and investigated with questionnaires from August to November in 2013.Univariate logistic regressions and multivariate logistic regressions were conducted to find the associations between social norms, smoking intention and quitting attempts. Results Smokers perceived low pro-quitting social norms from their family members, friends and other people around.With a 1 point increase in pro-quitting social norms score, smokers′ willingness to quit in the next 6 months increased by 69% (
8.Chromosome polymorphisms and their influence on semen quality and sperm DNA integrity in males undergoing IVF/ICSI.
Xian-Bao MAO ; Lin-Tao XUE ; Wei-Ying MO ; Yao-Xi MO ; Jun-Ping CHENG ; Shi-Kai WANG ; Yue-Yue HUANG ; Zheng-da LI ; Xiao-Hui ZHANG ; Ting-Ting ZHOU ; Ping-Pin WEI ; Wei-Hong TAN
National Journal of Andrology 2019;25(3):223-230
Objective:
To investigate the incidence of chromosome polymorphisms and their influence on semen quality and sperm DNA integrity in male patients receiving in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI).
METHODS:
We retrospectively analyzed the chromosomal karyotypes and the types and incidence rate of chromosome polymorphisms in 2 370 male patients undergoing IVF/ICSI between June 2016 and June 2018. We classified the patients into groups A (with variation in the secondary constriction region in the autosomal long arm), B (with variation in the short arm of the D/G group chromosomes), C (with interbrachial inversion of chromosome 9) and D (with Y chromosome polymorphisms), and compared the semen parameters and sperm DNA fragmentation indexes (DFI) between the patients with chromosome polymorphisms and those with normal chromosomes.
RESULTS:
Totally, 154 (6.50%) of the patients undergoing IVF/ICSI were found with chromosome polymorphisms, including 34 cases of secondary constriction variation in the long arm of the autosome (1.43% [34/2 370], 22.08% [34/154]), 82 cases of short arm polymorphisms of the D/G group chromosomes (3.46% [82/2 370], 53.25% [82/154]), 26 cases of interbrachial inversion of chromosome 9 (1.10% [26/2 370], 16.88% [26/154]), 10 cases of Y chromosome polymorphisms (0.42% [10/2 370], 6.50% [10/154]), and 2 cases of mixed chromosome polymorphisms (0.08% [2/2 370], 1.42% [2/154]). The total sperm count was lower in group D than in the other polymorphism groups and the normal chromosome group, but with no statistically significant difference among the five groups (P > 0.05). The sperm progressive motility was also lower in group D than in the other five groups, with statistically significant difference from group B (27.5 ± 13.5 vs. 41.5 ± 21.1, P = 0.027), but not from the other groups (P > 0.05). No statistically significant difference was observed in the sperm DFI between the polymorphism groups and the normal chromosome group (P > 0.05), or among the polymorphism groups (P > 0.05). The proportion of normal semen was lower in group D than in the other four groups, but with no statistically significant difference among the five groups (P > 0.05). The incidence rate of asthenospermia was higher in group D than in the other four groups, but with no statistically significant difference among the five groups (P > 0.05), and so was that of oligoasthenospermia, with statistically significant difference from the normal chromosome group (30.0% vs 8.0%, P = 0.041), but not from the other polymorphism groups (P > 0.05).
CONCLUSIONS
Short arm polymorphisms of the D/G group chromosomes are the most common type of chromosome polymorphisms in male patients undergoing IVF/ICSI. Polymorphisms of the Y chromosome have a negative effect on semen quality, while those of the other chromosomes do not significantly affect semen quality and sperm DNA integrity.
9.Chinese medicine syndromes in congestive heart failure: A literature study and retrospective analysis of clinical cases.
Xiao-Qian LI ; Jian-Cheng HE ; Pin-Xian HUANG ; Xue-Bin CAO
Chinese journal of integrative medicine 2016;22(10):738-744
OBJECTIVETo discuss the characteristics of Chinese medicine (CM) syndrome factors and distribution of congestive heart failure (CHF), and provide a basis for the diagnosis criteria of essential syndromes.
METHODSBased on databases of China National Knowledge Infrastructure (CNKI, 1980-2012) and Chinese Journal of Chongqing VIP Database (1989-2012), the eligible studies in CHF and extracted factors associated with compound syndromes were analyzed. All the syndromes were classified into deficiency, excess, and deficiency-excess in complexity syndrome were classified. Compound syndromes were separated into syndrome factors including single, double, three or four factors, along with the frequency of occurrence. The relation of CHF syndromes with age, gender, primary disease, brain natriuretic peptide (BNP) and cardiac functional grade was studied in 1,451 CHF cases (between December 2010 and September 2012), and the clinical distribution of common CHF syndromes was summarized.
RESULTSThe literature study involved 6,799 CHF cases in 66 literatures after screening. Of the different factors affecting CHF, qi deficiency was the most important one. In deficiency syndrome, Xin (Heart)-qi-deficiency was the most common single factor, and deficiency of both qi and yin was the most common double factor. The retrospective analysis involved 1,451 CHF cases (431 cases with test results of BNP). The xin blood stasis and obstruction and deficiency of both qi and yin syndrome were mostly seen in female patients, and phlegm-blocking-Xin-vessel and qi-deficiency-blood-stasis syndrome mostly in males. Xin-qi-deficiency and qi-deficiency-blood-stasis syndrome were mostly seen in patients aged 50-60 years. Patients aged over 60 years likely manifest deficiency of both qi and yin and Xin blood stasis and obstruction syndrome. The severity of syndrome is aggravated with increased BNP and cardiac functional grade.
CONCLUSIONSThe essential syndromes of CHF include qi-deficiency-blood-stasis and deficiency of both qi and yin. The clinical distribution is linked to patients' age and gender. BNP and cardiac functional grade is closely related to CHF syndromes, which may indicate the severity of CM syndromes of CHF.
Aged ; Aged, 80 and over ; Heart Failure ; therapy ; Humans ; Medicine, Chinese Traditional ; Middle Aged ; Natriuretic Peptide, Brain ; metabolism ; Retrospective Studies ; Syndrome
10.Inhibition of Alveolar Macrophage Pyroptosis Reduces Lipopolysaccharide-induced Acute Lung Injury in Mice.
Dong-Dong WU ; Pin-Hua PAN ; Ben LIU ; Xiao-Li SU ; Le-Meng ZHANG ; Hong-Yi TAN ; Zu CAO ; Zuo-Ren ZHOU ; Hai-Tao LI ; Hao-Si LI ; Li HUANG ; Yuan-Yuan LI
Chinese Medical Journal 2015;128(19):2638-2645
BACKGROUNDPyroptosis is the term for caspase-1-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.
METHODSC57BL/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-1-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.
RESULTSThe 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-α2 (IL-1α2) 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.
CONCLUSIONSThis 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.
Acute Lung Injury ; chemically induced ; prevention & control ; Amino Acid Chloromethyl Ketones ; pharmacology ; Animals ; Lipopolysaccharides ; toxicity ; Macrophages, Alveolar ; drug effects ; Male ; Mice ; Mice, Inbred C57BL ; Oligopeptides ; pharmacology ; Pyroptosis ; drug effects

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