1.Rectal Administration of Leek and Konjac-derived Extracellular Vesicles Alleviates High-fat Diet-induced Obesity in Mice via Gut Microbiota Modulation
Ya-Ru ZHANG ; Yu-Jia WU ; Cheng-Bang LIANG ; Xin-He YU ; Yan MU ; Yan TAN
Progress in Biochemistry and Biophysics 2026;53(5):1224-1239
ObjectiveObesity, a global chronic metabolic disease, is closely associated with disruptions in lipid metabolism and gut microbiota. Current intervention strategies still have limitations in terms of safety and microecological regulation, necessitating the exploration of novel natural regulatory approaches. Based on the early pathological characteristics of obesity, this study innovatively employs a rectal delivery method alongside a high-fat diet (HFD)-induced obesity model to systematically evaluate the inhibitory effects, safety, and gut microbiota regulation mechanisms of leek-derived and konjac-derived extracellular vesicles on obesity development. By simulating early clinical intervention scenarios, this study aims to explore the preventive potential of plant-derived extracellular vesicles during the initial stages of obesity onset. MethodsExtracellular vesicles from leek and konjac were isolated using ultracentrifugation combined with density gradient centrifugation. Their nanoscale properties were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). Male C57BL/6J mice were randomly divided into four groups: normal control (NC), high-fat diet (HFD), leek-derived extracellular vesicles (LEVs), and konjac-derived extracellular vesicles (KEVs). Beginning simultaneously with HFD feeding, mice in the intervention groups received 20 g/L vesicles rectally every 3 d for 4 weeks. Body mass and body composition were monitored throughout. At endpoint, mouse serum, adipose tissue, and colonic contents were collected. Serum biochemical indices (lipid profile, liver and kidney function, cardiac markers) were assessed to evaluate safety and metabolic efficacy, while 16S rRNA sequencing was employed to analyze gut microbial structure and diversity. ResultsDLS, NTA, and TEM confirmed that both LEVs and KEVs exhibited typical cup-shaped nanostructures with average particle sizes of approximately 284 nm and 223 nm, respectively. LEVs and KEVs treatment significantly suppressed HFD-induced weight gain and elevation of body-fat percentage (P<0.05), and reduced accumulation of abdominal white and epididymal adipose tissue. Serological analyses showed that both vesicles lowered total cholesterol, triglycerides and LDL-cholesterol, and ameliorated liver enzyme profiles (ALT, AST), demonstrating lipid-metabolic regulation and hepatoprotective effects. No hepatic, renal or cardiac dysfunction was observed, indicating favorable safety. Gut microbiota analyses revealed that vesicle intervention partially restored HFD-depleted microbial diversity and reshaped community structure. Notably, LEVs markedly increased the relative abundance of the beneficial taxon Lachnospiraceae at the family level, which is known for producing short-chain fatty acids and enhancing intestinal barrier function. Furthermore, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) functional prediction suggested that LEVs and KEVs modulated gut microbial functions through distinct mechanisms: LEVs downregulated pathways related to ribosomes and DNA replication while enhancing xenobiotic degradation, whereas KEVs tended to upregulate energy metabolism and protein synthesis toward healthy levels. ConclusionRectally administered LEVs and KEVs exhibit excellent safety and pronounced metabolic benefits during the early phase of obesity, suppressing weight gain, correcting lipid dysregulation, and exerting effects via modulation of gut microbial composition and function. This study provides systematic experimental evidence supporting plant-derived exosome-like vesicles as an early intervention strategy against obesity.
2.Rectal Administration of Leek and Konjac-derived Extracellular Vesicles Alleviates High-fat Diet-induced Obesity in Mice via Gut Microbiota Modulation
Ya-Ru ZHANG ; Yu-Jia WU ; Cheng-Bang LIANG ; Xin-He YU ; Yan MU ; Yan TAN
Progress in Biochemistry and Biophysics 2026;53(5):1224-1239
ObjectiveObesity, a global chronic metabolic disease, is closely associated with disruptions in lipid metabolism and gut microbiota. Current intervention strategies still have limitations in terms of safety and microecological regulation, necessitating the exploration of novel natural regulatory approaches. Based on the early pathological characteristics of obesity, this study innovatively employs a rectal delivery method alongside a high-fat diet (HFD)-induced obesity model to systematically evaluate the inhibitory effects, safety, and gut microbiota regulation mechanisms of leek-derived and konjac-derived extracellular vesicles on obesity development. By simulating early clinical intervention scenarios, this study aims to explore the preventive potential of plant-derived extracellular vesicles during the initial stages of obesity onset. MethodsExtracellular vesicles from leek and konjac were isolated using ultracentrifugation combined with density gradient centrifugation. Their nanoscale properties were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). Male C57BL/6J mice were randomly divided into four groups: normal control (NC), high-fat diet (HFD), leek-derived extracellular vesicles (LEVs), and konjac-derived extracellular vesicles (KEVs). Beginning simultaneously with HFD feeding, mice in the intervention groups received 20 g/L vesicles rectally every 3 d for 4 weeks. Body mass and body composition were monitored throughout. At endpoint, mouse serum, adipose tissue, and colonic contents were collected. Serum biochemical indices (lipid profile, liver and kidney function, cardiac markers) were assessed to evaluate safety and metabolic efficacy, while 16S rRNA sequencing was employed to analyze gut microbial structure and diversity. ResultsDLS, NTA, and TEM confirmed that both LEVs and KEVs exhibited typical cup-shaped nanostructures with average particle sizes of approximately 284 nm and 223 nm, respectively. LEVs and KEVs treatment significantly suppressed HFD-induced weight gain and elevation of body-fat percentage (P<0.05), and reduced accumulation of abdominal white and epididymal adipose tissue. Serological analyses showed that both vesicles lowered total cholesterol, triglycerides and LDL-cholesterol, and ameliorated liver enzyme profiles (ALT, AST), demonstrating lipid-metabolic regulation and hepatoprotective effects. No hepatic, renal or cardiac dysfunction was observed, indicating favorable safety. Gut microbiota analyses revealed that vesicle intervention partially restored HFD-depleted microbial diversity and reshaped community structure. Notably, LEVs markedly increased the relative abundance of the beneficial taxon Lachnospiraceae at the family level, which is known for producing short-chain fatty acids and enhancing intestinal barrier function. Furthermore, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) functional prediction suggested that LEVs and KEVs modulated gut microbial functions through distinct mechanisms: LEVs downregulated pathways related to ribosomes and DNA replication while enhancing xenobiotic degradation, whereas KEVs tended to upregulate energy metabolism and protein synthesis toward healthy levels. ConclusionRectally administered LEVs and KEVs exhibit excellent safety and pronounced metabolic benefits during the early phase of obesity, suppressing weight gain, correcting lipid dysregulation, and exerting effects via modulation of gut microbial composition and function. This study provides systematic experimental evidence supporting plant-derived exosome-like vesicles as an early intervention strategy against obesity.
3.Whole genome sequencing and analysis of multidrug resistant ST314 Salmonella Kentucky from a broiler slaughterhouse
Jia-rui LI ; Rui-yuan SUN ; Pei-jie HE ; Hao-tian LIU ; Ru-yi KUANG ; Jing XIA ; Min CUI ; Yong HUANG ; Li-kou ZOU ; Xin-feng HAN
Chinese Journal of Zoonoses 2025;41(5):537-543
This study investigated the potential pathogenicity and genetic characteristics of ST314 Salmonella Kentucky(S.Ken-tucky)isolates from a broiler slaughterhouse.Antimicrobial susceptibility testing and whole-genome sequencing(WGS)were used to determine antimicrobial resistance,virulence factors,and the presence of antimicrobial resistance genes(ARGs)and mobile genetic elements(MGEs)among the isolates.The three multidrug resistant(MDR)isolates exhibited high resistance to multiple antimicrobial agents.The F4-2S strain exhibited resistance to 14 drugs across seven categories,whereas the F4T strain showed resistance to 13 drugs in the same number of categories.In contrast,the Y23 strain was resistant to nine drugs in six categories.Notably,F4-2S dem-onstrated high homology with F4T:both possessed 13 ARGs distributed across nine categories,in addition to a wide range of virulence factors,including secretion systems and effector proteins.The presence of IncR and IncX1 plasmids significantly enhanced both the antimicrobial resistance and pathogenicity of the isolates.The genome map of Y23 revealed a chromosome alongside two plasmids.The chromosome containedonly one resistance gene but several virulence factors,including the type III secretion system(T3SS),which is crucial for bacterial invasion.The plasmid pY23-1 contained eight types of 19 ARGs.Comparative analysis indicated that pY23-1 ex-hibited high homology with pZ1323SSL0055 and pSAL-045,all of which contained multiple ARGs,thus suggesting critical roles of these genes in the evolution of bacterial resistance.In conclusion,ST314 S.Kentucky demonstrated a complex mechanism of resis-tance coupled with significant pathogenic potential.The ARGs and MGEs in the plasmid contributed to the emergence and dissemina-tion of antimicrobial resistance.The multiple virulence factors present in the chromosome may be key factors driving the increasing virulence of ST314 S.Kentucky.
4.Analysis of tobacco use situation and related factors among occupational population in Beijing in 2018
Jianhui HUANG ; Ru ZHENG ; Li QI ; Guan WANG ; Ying SUN ; Jiali DUAN
Chinese Journal of Preventive Medicine 2025;59(5):634-639
Objective:To understand the tobacco use situation and related factors among the occupational population in Beijing in 2018.Methods:The data were obtained from a special survey on “Healthy Beijing People—Ten-year Action Plan for Health Promotion (2009—2018)”. From June to September 2018, 12 908 participants were recruited from 16 districts of Beijing using the stratified sampling method combined with the typical sampling method. Questionnaires were conducted to collect basic information, work situations, tobacco exposure in public places, and smoking cessation. The Chi-square test was used to compare the differences in current smoking rates, smoking cessation rates and second-hand smoke exposure rates among participants with different characteristics. Multivariate logistic regression analysis was used to analyze the related factors of tobacco use.Results:The present smoking rate of the occupational population in Beijing was 18.0% (95% CI: 17.3%-18.7%), and the passive smoking exposure rate of non-smokers was 61.0% (95% CI: 60.1%-61.9%). The smoking cessation rate among the working population was 22.2% (95% CI: 20.7%-23.7%), and the proportion of current smokers with the intention to quit was 63.9% (1 485/2 325). The present smoking rate of employees of different genders, ages, education levels and occupational nature showed statistically significant differences ( P<0.05). The results of multivariate logistic regression analysis showed that in males, compared with the age group of 16-29 years old, the risk of smoking increased in the age groups of 30-39 years old, 40-49 years old and over 50 years old [ OR (95% CI) values were 1.49 (1.27-1.74), 1.34 (1.13-1.59) and 1.30 (1.06-1.59)]. Compared with those with junior high school or lower education, participants with high school/vocational/college education group had a higher risk of smoking ( OR=1.38, 95% CI: 1.13-1.69), while those with master′s degree or above had a lower risk of smoking ( OR=0.30, 95% CI: 0.22-0.42). The physical workers ( OR=1.28, 95% CI: 1.11-1.47) had a higher risk of smoking than the mental workers. Conclusion:The current smoking rate among the occupational population in Beijing is lower than the national level during the same period, but the exposure rate to second-hand smoke is relatively high. Age, educational level, job nature and gender are related factors of smoking.
5.Knowledge, attitude and practice of salt reduction and hypertension status and related factors among restaurant practitioners in Beijing City
Jianhui HUANG ; Jingjuan REN ; Ru ZHENG ; Fei XU ; Yan QU ; Jiali DUAN ; Ye HAN
Chinese Journal of Preventive Medicine 2025;59(8):1299-1304
A convenience sampling method was employed to recruit 445 food service employees from 67 Chinese restaurants across all 16 administrative districts of Beijing City from August to December in 2022. A questionnaire survey was conducted to assess their knowledge, attitudes, and behaviors regarding salt reduction and hypertension. The results revealed that awareness was highest for the statement "Hypertensive patients should reduce salt intake" (88.3%), while awareness of "China′s diagnostic criteria for hypertension" was the lowest (23.8%). Positive attitude endorsement rates were 96.0% for willingness to reduce salt, 95.3% for perceived self-efficacy in salt reduction, and 93.0% for agreement with a low-salt diet. Regarding behaviors, the rates of actively reducing salt when ordering takeout or dining out, using low-sodium salt, and using salt-reducing spoons were 73.7%, 45.4%, and 55.5%, respectively. The overall compliance rate for salt-reduction related behaviors was 73.9%. Multivariable logistic regression analysis demonstrated that: compared to the 18-29 age group, employees aged 30-39 ( OR=2.19, 95% CI: 1.16-4.14), 40-49 ( OR=3.36, 95% CI: 1.52-7.42), and 50-59 ( OR=3.25, 95% CI: 1.25-8.50) were significantly more likely to achieve compliance with salt-reduction behaviors; chefs were significantly more likely to achieve behavioral compliance compared to managerial staff ( OR=2.08, 95% CI: 1.08-3.98); employees in catering with adequate knowledge about salt reduction and hypertension were significantly more likely to exhibit behavioral compliance compared to those with inadequate knowledge ( OR=3.32, 95% CI: 1.83-5.92); employees in catering with positive attitudes towards salt reduction were significantly more likely to achieve behavioral compliance compared to those with negative attitudes ( OR=5.81, 95% CI: 2.05-16.43). In conclusion, food service employees in Beijing exhibit insufficient knowledge about salt intake and hypertension. While they demonstrate strong willingness to reduce salt, this does not consistently translate into action. Compliance with salt-reduction behaviors is influenced by age, education level, and job position. There is an urgent need to strengthen the dissemination of knowledge regarding high salt intake and hypertension and to implement personalized interventions targeting salt-reduction behaviors and skills.
6.Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury (version 2025)
Kai HUANG ; Lunhao BAI ; Qing BI ; Hong CHEN ; Jiwu CHEN ; Xuesong DAI ; Wenyong FEI ; Weili FU ; Zhizeng GAO ; Lin GUO ; Yinghui HUA ; Jingmin HUANG ; Suizhu HUANG ; Xuan HUANG ; Jian LI ; Qiang LI ; Shuzhen LI ; Yanlin LI ; Yunxia LI ; Zhong LI ; Ning LIU ; Yuqiang LIU ; Wei LU ; Hongbin LYU ; Haile PAN ; Xiaoyun PAN ; Chao QI ; Weiliang SHEN ; Luning SUN ; Jin TANG ; Zimin WANG ; Bide WANG ; Ru WANG ; Shaobai WANG ; Licheng WEI ; Weidong XU ; Yongsheng XU ; Jizhou YANG ; Liang YANG ; Rui YANG ; Hongbo YOU ; Tengbo YU ; Jiakuo YU ; Bing YUE ; Hua ZHANG ; Hui ZHANG ; Qingsong ZHANG ; Xintao ZHANG ; Jiajun ZHAO ; Lilian ZHAO ; Qichun ZHAO ; Song ZHAO ; Jiapeng ZHENG ; Jiang ZHENG ; Zhi ZHENG ; Jingbin ZHOU ; Jinzhong ZHAO
Chinese Journal of Trauma 2025;41(4):325-338
With the rapid development of competitive sports, the incidence of anterior cruciate ligament (ACL) injury is on the rise. Such injuries may shorten athletes′ career and lead to other long-term adverse consequences. Although athletes generally recover well after ACL reconstruction, many still struggle to return to their pre-injury performance levels. Advances in the understanding of ACL anatomy and injury mechanisms, along with the evolution of surgical techniques and rehabilitation methods, have provided more individualized and tailored options for athletes following ACL injuries. However, there is currently no consensus in China regarding surgical and rehabilitation strategies for competitive athletes aiming to return to sports after ACL injuries. To this end, the Sports Medicine Committee of the Chinese Research Hospital Association and the Editorial Board of the Chinese Journal of Trauma jointly formulated the Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury ( version 2025), and presented 14 recommendations covering surgical indications, preoperative rehabilitation, surgical timing, surgical strategies and postoperative rehabilitation strategies, aiming to improve the surgical treatment and rehabilitation system for ACL injuries in competitive athletes and facilitate their return to high-level sports performance after injury.
7.The efficacy of combining mirror therapy with pneumatic flexible glove training in treating post-stroke hand dysfunction
Cuifeng WEN ; Hao HUANG ; Ru YA ; Yulong BAI ; Xiaowen WANG ; Haoming SONG
Chinese Journal of Physical Medicine and Rehabilitation 2025;47(10):914-921
Objective:To observe the effectiveness of combining mirror therapy with pneumatic flexible glove training in treating hand dysfunction after a stroke. Its effect on cerebral cortex activation was documented using near-infrared functional imaging of the brain.Methods:A total of 84 stroke survivors with hand dysfunction were randomly divided into a Mirror Group, a Glove Group and a Combined Group, each of 28. In addition to standard rehabilitation training, the Glove Group received 20 minutes of training with a pneumatic soft glove, 5 days per week for 6 consecutive weeks. The Mirror Group received mirror therapy (MT). The Combined Group was given both simultaneously. Before and after the treatment, everyone′s upper limb functioning was evaluated (using the Fugl-Meyer Upper Limb Assessment (FMA-U)), along with their hand motor skills (using the Arm Action Test (ARAT)) and their ability in daily living activities (using the Barthel Index (BI)). Functional near-infrared spectroscopy (fNIRS) was employed to measure any changes in oxygenated hemoglobin (HBO) concentration at 730nm and 850nm wavelengths.Results:The FMA-U, ATAT and BI scores in both the proximal and distal regions of all three groups showed significant improvement after the treatments compared to pre-treatment levels. The combined group demonstrated significantly better distal FMA-U and ARAT scores after the treatment (12.25±8.80 and 20.93±15.68 respectively), outperforming both the glove and mirror groups. The infrared spectroscopy revealed that bilateral SM1 activation, affected-side somatosensory association cortex (SAC) and supplementary motor cortex excitability in both the mirror and combined groups were significantly better than among the glove group after the experiment.Conclusions:Combined with pneumatic flexible glove training, mirror therapy can not only significantly improve the hand function of stroke survivors, but also activate the relevant brain regions of both hemispheres through bilateral motor patterns combined with multisensory stimulation, promoting the balance between hemispheres.
8.Comparison of clinical outcomes between modified posterolateral approach and traditional posterolateral approach internal fixation in treatment of trimalleolar fracture
Chao-ming HUANG ; Shao-xiang XIA ; Ru PEI ; Jie ZHANG ; Ren-hao HE
Journal of Regional Anatomy and Operative Surgery 2025;34(5):413-416
Objective To compare the clinical outcomes of modified posterolateral approach and traditional posterolateral approach combined with open reduction and internal fixation via medial approach in treatment of trimalleolar fracture.Methods Sixty-two patients with trimalleolar fractures who underwent modified posterolateral approach combined with open reduction and internal fixation via medial approach from January 2019 to June 2022 in orthopedics department of our hospital were enrolled in the modified approach group,and 62 patients who underwent traditional posterolateral approach combined with open reduction and internal fixation via medial approach at the same period were matched as the traditional approach group.The perioperative indicators were collected.The range of ankle motion 12 months after surgery was measured.The Maryland score,American Orthopaedic Foot and Ankle Society(AOFAS)score and Baird-Jackson score were employed to evaluate the recovery of patients 12 months after surgery,and the occurence of complications was recorded.Results There was no significant difference in the operation time,intraoperative blood loss,incision length,postoperative drainage volume or pain score between the two groups(P<0.05).The Maryland scores,AOFAS scores and Baird-Jackson scores 12 months after surgery of the two groups were higher than those before operation(P<0.05),while there was no significant difference between the two groups(P<0.05).The range of ankle motion in the modified approach group was better than that in the traditional approach group,and the incidence of nerve injury after surgery was lower than that in the traditional approach group,with statistically significant differences(P<0.05).Conclusions The modified posterolateral approach combined with open reduction and internal fixation via medial approach in treatment of trimalleolar fracture can achieve good early clinical outcome,effectively improve range of ankle motion,and reduce postoperative nerve injury.
9.Qingda Granule Attenuates Hypertension-Induced Cardiac Damage via Regulating Renin-Angiotensin System Pathway.
Lin-Zi LONG ; Ling TAN ; Feng-Qin XU ; Wen-Wen YANG ; Hong-Zheng LI ; Jian-Gang LIU ; Ke WANG ; Zhi-Ru ZHAO ; Yue-Qi WANG ; Chao-Ju WANG ; Yi-Chao WEN ; Ming-Yan HUANG ; Hua QU ; Chang-Geng FU ; Ke-Ji CHEN
Chinese journal of integrative medicine 2025;31(5):402-411
OBJECTIVE:
To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved.
METHODS:
Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively.
RESULTS:
The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01).
CONCLUSIONS
Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals
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Drugs, Chinese Herbal/therapeutic use*
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Hypertension/pathology*
;
Renin-Angiotensin System/drug effects*
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Rats, Inbred SHR
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Oxidative Stress/drug effects*
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Male
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Rats, Inbred WKY
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Blood Pressure/drug effects*
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Myocardium/pathology*
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Rats
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Inflammation/pathology*
10.Resveratrol Attenuates Inflammation in Acute Lung Injury through ROS-Triggered TXNIP/NLRP3 Pathway.
Wen-Han HUANG ; Kai-Ying FAN ; Yi-Ting SHENG ; Wan-Ru CAI
Chinese journal of integrative medicine 2025;31(12):1078-1086
OBJECTIVE:
To evaluate the protective effects of resveratrol against acute lung injury (ALI) and investigate the potential mechanisms underlying the reactive oxygen species (ROS)-triggered thioredoxin-interacting protein (TXNIP)/NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) pathway.
METHODS:
C57BL/6 mice and J774A.1 cells were selected as the research subjects. Thirty Mice were randomly divided into 5 groups of 6 in each group: control with 0.9% saline, 5 mg/kg lipopolysaccharide (LPS) 24 h, 25 mg/kg resveratrol + 5 mg/kg LPS, 100 mg/kg resveratrol + 5 mg/kg LPS, and 4 mg/kg NLRP3 inhibitor CY-09 + 5 mg/kg LPS. For cell stimulation, cells were pretreated with 5 and 20 µmol/L resveratrol for 2 h, and stimulated with or without 1 µg/mL LPS and 3 mmol/L ATP for 2 h. The antioxidant N-acetyl-L-cysteine (NAC, 2 µmol/L) was used as the positive control group. Hematoxylin and eosin staining was used to evaluate the degree of lung LPS-induced tissue damage, and enzyme-linked immunosorbent assay was used to evaluate the contents of interleukin-1 β (IL-1 β) and IL-18 in the serum and cell supernatant. ROS and malondialdehyde (MDA) levels in the lung tissue were detected using the corresponding kits. Western blotting was used to detect the expressions of TXNIP, high-mobility group box 1 (HMGB1), NLRP3, as well as cysteine-aspartic acid protease 1 (caspase-1) and gasdermin D (GSDMD) along with their cleaved forms in lung tissue. Additionally, reverse transcription quantitative polymerase chain reaction was performed to analyze the expression of related inflammatory cytokines. ROS content was detected using flow cytometry and confocal laser microscopy. Mitochondrial morphological changes were observed using transmission electron microscopy, and HMGB1 expression was detected using immunofluorescence.
RESULTS:
Resveratrol significantly alleviated LPS-induced lung damage with reduced inflammation, interstitial edema, and leukocyte infiltration (P<0.01). It also decreased serum levels of IL-1 β and IL-18 (P<0.05), while downregulating the expressions of NLRP3, IL-6, and other inflammatory markers at both the protein and mRNA levels (P<0.05). Notably, the higher dose (100 mg/kg) demonstrated a better effect than the lower dose (25 mg/kg). In macrophages, resveratrol reduced IL-1 β and IL-18 following LPS and ATP stimulation, suppressed HMGB1 translocation, and inhibited formation and activation of the NLRP3 inflammasome (P<0.05 or P<0.01). These anti-inflammatory effects were mediated through the suppression ROS accumulation (P<0.01) and mitochondrial dysfunction. Transmission electron microscopy revealed that resveratrol preserved mitochondrial structure, preventing the mitochondrial damage seen in LPS-treated groups (P<0.01). The expressions of cleaved caspase-1, cleaved GSDMD, and cytoplasmic HMGB1 were all reduced following resveratrol treatment (P<0.01). Moreover, resveratrol inhibited dissociation of TXNIP from thioredoxin, blocking subsequent activation of NLRP3 and downstream inflammatory cytokines (P<0.01). Similarly, the higher concentration of resveratrol (20 µ mol/L) exhibited superior efficacy in vitro.
CONCLUSION
Resveratrol can reduce the inflammatory response following ALI and inhibit the activation of NLRP3 inflammasome and the level of HMGB1 in the cytoplasm by inhibiting ROS overproduction.
Acute Lung Injury/metabolism*
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NLR Family, Pyrin Domain-Containing 3 Protein/metabolism*
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Animals
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Resveratrol/pharmacology*
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Reactive Oxygen Species/metabolism*
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Inflammation/complications*
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Mice, Inbred C57BL
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Carrier Proteins/metabolism*
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Signal Transduction/drug effects*
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Lipopolysaccharides
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Thioredoxins/metabolism*
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Mice
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Lung/drug effects*
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Male
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Cell Line
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Interleukin-1beta/metabolism*
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Cell Cycle Proteins
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Stilbenes/therapeutic use*

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