1.Steroids combined with anticoagulant in acute/subacute severe cerebral venous thrombosis.
Shimin HU ; Yaqin GU ; Tingyu ZHAO ; Kaiyuan ZHANG ; Jingkai LI ; Chen ZHOU ; Haiqing SONG ; Zhi LIU ; Xunming JI ; Jiangang DUAN
Chinese Medical Journal 2025;138(15):1825-1834
BACKGROUND:
Inflammation plays a critical role in severe cerebral venous thrombosis (CVT) pathogenesis, but the benefits of anti-inflammatory therapies remain unclear. This study aimed to investigate the association between steroid therapy combined with anticoagulation and the prognosis of acute/subacute severe CVT patients.
METHODS:
A prospective cohort study enrolled patients with acute/subacute severe CVT at Xuanwu Hospital (July 2020-January 2024). Patients were allocated into steroid and non-steroid groups based on the treatment they received. Functional outcomes (modified Rankin scale [mRS]) were evaluated at admission, discharge, and 6 months after discharge. Serum high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), cerebrospinal fluid (CSF) IL-6, and intracranial pressure were measured at admission and discharge in the steroid group. Fundoscopic Frisén grades were assessed at admission and 6 months after discharge. Univariate and multivariate logistic regression were used to evaluat associations between steroid use and favorable outcomes (mRS ≤2) at the 6-month follow-up. Paired tests assessed changes in hs-CRP and other variables before and after treatment, and Spearman's correlations were used to analyze relationships between these changes and functional improvements.
RESULTS:
A total of 107 and 58 patients in the steroid and non-steroid groups, respectively, were included in the analysis. Compared with the non-steroid group, the steroid group had a higher likelihood of achieving an mRS score of 0-2 (93.5% vs . 82.5%, odds ratio [OR] = 2.98, P = 0.037) at the 6-month follow-up. After adjusting for confounding factors, the result remained consistent. Pulsed steroid therapy did not increase mortality during hospitalization or follow-up, nor did it lead to severe steroid-related complications (all P >0.05). Patients in the steroid group showed a significant reduction in serum hs-CRP, IL-6, CSF IL-6, and intracranial pressure at discharge compared to at admission, as well as a significant reduction in the fundoscopic Frisén grade at the 6-month follow-up compare to at admission (all P <0.001). A reduction in serum inflammatory marker levels during hospitalization positively correlated with improvements in functional outcomes ( P <0.05).
CONCLUSION:
Short-term steroid use may be an effective and safe adjuvant therapy for acute/subacute severe CVT when used alongside standard anticoagulant treatments, which are likely due to suppression of the inflammatory response. However, these findings require further validation in randomized controlled trials.
TRAIL REGISTRATION
ClinicalTrials.gov , NCT05990894.
Adult
;
Aged
;
Female
;
Humans
;
Male
;
Middle Aged
;
Anticoagulants/therapeutic use*
;
C-Reactive Protein/metabolism*
;
Interleukin-6/metabolism*
;
Intracranial Thrombosis/drug therapy*
;
Prospective Studies
;
Steroids/therapeutic use*
;
Venous Thrombosis/drug therapy*
2.Mechanism of 4-methylcatechol in inhibiting fibroblast-like synoviocyte migration and suppressing inflammatory responses in treatment of rheumatoid arthritis.
Zhendong YING ; Peng WANG ; Lei ZHANG ; Dailing CHEN ; Qiuru WANG ; Qibin LIU ; Tiantian TANG ; Changjun CHEN ; Qingwei MA
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(8):1051-1060
OBJECTIVE:
To investigate the effects of 4-methylcatechol (4MC) on the migration and inflammatory response in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS), as well as its underlying mechanisms of action.
METHODS:
RA-FLS was isolated from synovial tissue donated by RA patients, and the optimal concentration of 4MC was determined by cell counting kit 8 method for subsequent experiments, and the effect of 4MC on the migratory ability of RA-FLS was evaluated via a cell scratch assay. An inflammation model of RA-FLS was induced by tumor necrosis factor α (TNF-α). Real-time fluorescence quantitative PCR and ELISA were employed to detect the gene and protein expression levels of interleukin-1β (IL-1β) and IL-6 in RA-FLS and their culture supernatants, respectively, thereby investigating the anti-inflammatory effects of 4MC. Western blot was used to examine the expressions of nuclear factor κB (NF-κB) signaling pathway-related proteins, including inhibitor of NF-κB-α (IKBα), phosphorylated (P)-IκBα, NF-κB-inducing kinase α (IKKα), P-IKKαβ, P-p65, and p65. Cellular immunofluorescence was utilized to detect the expression and localization of p65 in RA-FLS, exploring whether 4MC exerts its anti-inflammatory effects by regulating the NF-κB signaling pathway. Finally, a collagen-induced arthritis (CIA) mouse model was established. The anti-RA effect of 4MC in vivo was evaluated by gross observation and histological examination.
RESULTS:
4MC inhibited RA-FLS migration in a concentration-dependent manner. In the TNF-α-induced RA-FLS inflammation model, 4MC significantly decreased the gene and protein expression levels of IL-1β and IL-6. Furthermore, 4MC markedly reduced the ratios of P-IΚBα/IΚBα, P-IKKαβ/IKKα, and P-p65/p65, thereby blocking the transcriptional activity of p65 by inhibiting its nuclear translocation. This mechanism effectively suppressed the activation of the TNF-α-mediated NF-κB signaling pathway. Animal studies demonstrated that 4MC [10 mg/(kg·day)] significantly lowered serum levels of IL-1β, IL-6, and TNF-α, and alleviated arthritis severity and bone destruction in CIA mice.
CONCLUSION
4MC not only inhibits the migration of RA-FLS but also mitigates their inflammatory response by suppressing the NF-κB signaling pathway, thereby effectively exerting its anti-RA effects.
Synoviocytes/metabolism*
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Arthritis, Rheumatoid/metabolism*
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Animals
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Cell Movement/drug effects*
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Humans
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Catechols/therapeutic use*
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Fibroblasts/drug effects*
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Mice
;
Tumor Necrosis Factor-alpha/pharmacology*
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Interleukin-1beta/metabolism*
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Interleukin-6/metabolism*
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Signal Transduction/drug effects*
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NF-kappa B/metabolism*
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Transcription Factor RelA/metabolism*
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Synovial Membrane/cytology*
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Cells, Cultured
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Male
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Arthritis, Experimental
;
Anti-Inflammatory Agents/pharmacology*
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NF-KappaB Inhibitor alpha
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Inflammation
3.Role of antibiotic eluting absorbable calcium sulfate in phaseⅠrevision treatment of periprosthetic knee infection.
Xiao-Bo CHEN ; Shuai-Lei LI ; Ai-Bin LIU ; Hao CHAI ; Yong-Qiang SUN
China Journal of Orthopaedics and Traumatology 2025;38(6):580-586
OBJECTIVE:
To explore the role of antibiotic-eluting absorbable calcium sulfate in treating periprosthetic infection after one-stage revision of knee arthroplasty.
METHODS:
A retrospective analysis was performed on 36 patients(36 knees)who underwent phaseⅠrevision for periprosthesis infection after total knee arthroplasty from January 2018 to March 2022. All patients were underwent knee cavity puncture before operation and had positive results of aseptic body fluid culture, 21 patients received revision combined with antibiotic loaded calcium sulfate at stageⅠ(calcium sulfate group) during operation, and 15 patients underwent renovation at stageⅠ(revision group). There were 9 males and 12 females in calcium sulfate group, aged from 54 to 76 years old with an average of(67.6±6.2) years old. There were 15 patients in revision group, including 4 males and 11 females, aged from 60 to 75 years old with average of (69.6±4.1) years old. The levels of serum C-reactive protein (CRP), interleukin-6 (IL-6) at 7, 14, 30 and 90 days after operation were compared between two groups, and the rate of end-infection control at follow-up were compared. The systemic antibiotic application time, hospital stay and postoperative complications were observed between two groups.
RESULTS:
Calcium sulfate group were followed up for 12 to 29 months with an average of(18.9±4.2) months, and the infection control rate was 90.5%;while revision group were followed up 18 to 29 months with average of (21.6±3.7) months, and the infection control rate was 86.7% (13/15). There were no significant differences in follow-up time and infection control rate between two groups(P>0.05). Postoperative levels of CRP and IL-6 at 7, 14 and 30 days in calcium sulfate group were (32.79±11.48), (15.50±6.52), (9.36±3.32) mg·L-1 and (17.31±6.15) pg·ml-1, respectively;which were lower than those in revision group (40.65±11.32), (30.15±10.57), (18.97±5.86) mg·L-1 and (25.54±6.73) pg·ml-1, had statistical differences(P<0.05). There were no significant differences in IL-6 levels at 7 and 14 days after operation and CRP levels at 90 days after operation between two groups (P>0.05). The hospitalization time and systemic antibiotic application time in calcium sulfate group were (18.4±2.2) and (63.5±21.4) d, respectively;which were better than those in revision group (20.5±2.4) and (82.7±16.9) d, and had statistical differences(P<0.05). No significant wound complications and hypercalcemia were observed in calcium sulfate group.
CONCLUSION
Antibiotic eluted absorbable calcium sulfate could be used to treat periprosthetic knee infection, significantly reducing CRP levels in the early postoperative period, shortening hospital stay and systemic antibiotic application time, but it does not significantly improve the control rate of revision infection at stageⅠ.
Humans
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Male
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Female
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Aged
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Prosthesis-Related Infections/surgery*
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Middle Aged
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Calcium Sulfate/administration & dosage*
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Arthroplasty, Replacement, Knee/adverse effects*
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Retrospective Studies
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Anti-Bacterial Agents/therapeutic use*
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Interleukin-6/blood*
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C-Reactive Protein/metabolism*
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Reoperation
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Knee Prosthesis/adverse effects*
4.Research on the anti-inflammatory effects of a novel sleep-aid decoction on elderly insomnia patients across traditional Chinese medicine constitutional types.
Zhen WU ; Zhuoqiong BIAN ; Ailin CHEN ; Qiuping ZHANG ; Jie LI ; Hui ZHOU ; Hongying ZHU
Chinese Journal of Cellular and Molecular Immunology 2025;41(11):1007-1012
Objective To evaluate the clinical efficacy of a novel sleep-aid decoction in treating elderly insomnia patients with different traditional Chinese medicine (TCM) constitutional types, and its effects on neurotransmitter and inflammatory factor levels. Methods A total of 200 patients with four different TCM constitutions-peaceful, Qi-deficient, Yin-deficient, and Yang-deficient-were recruited. Peripheral blood neurotransmitter and inflammatory factor levels were measured for variations among insomnia patients across different constitutions. These patients were treated using the novel sleep-aid decoction, the effects of which were evaluated based on changes in neurotransmitters and inflammatory factors. Results Compared to the peaceful constitution group, insomnia patients with Qi-deficient, Yin-deficient, and Yang-deficient constitutions exhibited significantly elevated baseline levels of neurotransmitters (5-HT, GABA) and inflammatory factors (IL-6, TNF-α, IL-1β, CRP). Following the treatment, the Qi-deficient and Yin-deficient groups showed a marked increase in 5-HT levels, restored balance of Glu, GABA, and melatonin, and significant reductions in IL-6 and TNF-α levels. The overall effective rate was 83.5%, with optimal efficacy observed in the Qi-deficient (97.72%) and Yin-deficient (95.34%) groups. Conclusion The novel sleep-aid decoction is effective in treating insomnia in elderly patients, with the best results observed in the Qi-deficient and Yin-deficient constitution groups.
Humans
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Sleep Initiation and Maintenance Disorders/blood*
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Aged
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Male
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Female
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Drugs, Chinese Herbal/therapeutic use*
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Medicine, Chinese Traditional
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Middle Aged
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Tumor Necrosis Factor-alpha/blood*
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Sleep Aids, Pharmaceutical/therapeutic use*
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Anti-Inflammatory Agents/therapeutic use*
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Interleukin-6/blood*
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Interleukin-1beta/blood*
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Neurotransmitter Agents/blood*
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Aged, 80 and over
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C-Reactive Protein/metabolism*
5.Vitexin-4 ″-O-glucoside alleviates acetaminophen-induced acute liver injury.
Fan DONG ; Shanglei LAI ; Jiannan QIU ; Xiaobing DOU
Journal of Zhejiang University. Medical sciences 2025;54(3):307-317
OBJECTIVES:
To explore the protective effect of vitexin-4 ″-O-glucoside (VOG) against acetaminophen-induced acute liver injury in mice and its underlying mechanism.
METHODS:
C57BL/6 mice were randomly divided into 4 groups: normal control group, model control group, low-dose group of VOG (30 mg/kg), and high-dose group of VOG (60 mg/kg). Acute liver injury was induced by intraperitoneal injection of acetaminophen (500 mg/kg). VOG was administrated by gavage 2 h before acetaminophen treatment in VOG groups. The protective effect of VOG against acute liver injury was evaluated by detecting alanine transaminase (ALT), aspartate transaminase (AST) levels and hematoxylin and eosin staining. The malondialdehyde (MDA) content, superoxide dismutase (SOD) and catalase (CAT) activity in liver were detected to evaluate the hepatic oxidative stress. The expression levels of tumor necrosis factor (TNF)-α, Il-1β, and Il-6 in liver were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The expression levels of phosphorylated c-jun N-terminal kinase (JNK)/JNK, phosphorylated p38/p38, inositol-requiring enzyme 1 alpha (IRE-1α), X-box binding protein 1s (XBP1s), and glucose-regulated protein 78 (GRP78) in liver were detected by Western blotting. An endoplasmic reticulum stress model was established in AML-12 cells using tunicamycin. Cell viability was assessed using the CCK-8 assay, and the degree of cell damage was detected by lactate dehydrogenase (LDH) assay. The gene expression levels of Ire-1α, Xbp1s, and Grp78 in the cells were detected using qRT-PCR.
RESULTS:
In the animal experiments, compared with the model control group, VOG significantly improved plasma ALT and AST levels, liver MDA content, as well as SOD and CAT activities. VOG also reduced the expression levels of Tnf-α, Il-1β, and Il-6 in the liver, and improved protein phosphorylation levels of JNK and p38, as well as the protein expression levels of IRE-1α, XBP1s, and GRP78. In cell experiments, VOG pretreatment enhanced cell viability, reduced LDH release and decreased the mRNA expression of Ire-1α, Xbp1s, and Grp78.
CONCLUSIONS
VOG can suppress inflammation and oxidative stress, and alleviate acetaminophen-induced acute liver injury in mice by suppressing endoplasmic reticulum stress and modulating the MAPK signaling pathway.
Animals
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Endoplasmic Reticulum Chaperone BiP
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Mice
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Acetaminophen/adverse effects*
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Mice, Inbred C57BL
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Chemical and Drug Induced Liver Injury/prevention & control*
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Glucosides/therapeutic use*
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Oxidative Stress/drug effects*
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Male
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Apigenin/therapeutic use*
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Liver/drug effects*
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Tumor Necrosis Factor-alpha/metabolism*
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Endoplasmic Reticulum Stress/drug effects*
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X-Box Binding Protein 1
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Endoribonucleases/metabolism*
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Interleukin-1beta/metabolism*
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Interleukin-6/metabolism*
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Protein Serine-Threonine Kinases
6.Effects of nebulized self-developed Zangsiwei Qingfei Mixture on airway inflammation in cigarette smoke-induced COPD mice and a network pharmacology analysis.
Meizhi LI ; Fei PENG ; Quan ZHANG ; Yanna WU ; Jingping SUN ; Si LEI ; Shangjie WU
Journal of Central South University(Medical Sciences) 2025;50(7):1113-1125
OBJECTIVES:
Chronic obstructive pulmonary disease (COPD) is a major chronic respiratory condition with high morbidity and mortality, imposing a serious economic and public health burden. The World Health Organization ranks COPD among the top 4 chronic diseases worldwide. Zangsiwei Qingfei Mixture (ZSWQF), a novel Tibetan herbal formulation independently developed by our research team, has shown therapeutic potential for chronic respiratory diseases. This study aims to evaluate the effects of aerosolized ZSWQF on cigarette smoke-induced COPD in mice and explore its underlying mechanisms.
METHODS:
Thirty C57 mice were randomly divided into a Control group, a COPD group, and a ZSWQF group. The Control group received saline aerosol inhalation without cigarette smoke exposure; both the COPD group and the ZSWQF group were exposed to cigarette smoke, with the former receiving saline inhalation and the latter treated with ZSWQF aerosol. White blood cell (WBC) count was performed using a fully automatic blood cell analyzer. Serum, alanine transaminase (ALT), and serum creatinine (SCr), as well as interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α levels in serum and bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). BALF cell classification was determined using a hematology analyzer. Lung function was assessed with a small animal pulmonary function system, including airway resistance (RI) and cyclic dynamic compliance (CyDN). Lung tissues were stained with hematoxylin and eosin (HE), and mean linear intercept (MLI) and destruction index (DI) were calculated to evaluate morphological changes. Network pharmacology was applied to identify disease-related and ZSWQF-related targets, followed by intersection and protein-protein interaction (PPI) network analysis, and enrichment analysis of biological functions and pathways. Primary type II alveolar epithelial cell (AEC II) from SD rats were isolated and divided into a Control group, a lipopolysaccharide (LPS) group, a normal serum group, a water extract of ZSWQF (W-ZSWQF) group, a ZSWQF containing serum group, and a MLN-4760 [angiotensin-converting enzyme (ACE) 2 inhibitor]. Western blotting was performed to assess protein expression of ACE, p38 [a mitogen-activated protein kinase (MAPK)], phospho (p)-p38, extracellular signal-regulated kinases 1 and 2 (ERK1/2), p-ERK1/2, c-Jun N-terminal kinase (JNK), p-JNK, inhibitor of nuclear factor-kappa B alpha (IκBα), p-IκBα, and p-p65 subunit of nuclear factor-kappa B (NF-κBp65).
RESULTS:
WBC counts were significantly higher in the COPD group than in controls (P<0.01) and decreased following ZSWQF treatment (P<0.05). No significant intergroup differences were found in organ weights, ALT, or SCr (all P>0.05). Serum and BALF levels of IL-6, IL-8, and TNF-α, as well as total BALF cells, neutrophils, and macrophages, were elevated in the COPD group compared with controls and reduced by ZSWQF treatment (P<0.05). COPD mice exhibited increased RI, decreased CyDN, marked alveolar congestion, inflammatory infiltration, thickened septa, and higher MLI and DI values versus controls (P<0.05); ZSWQF treatment significantly reduced MLI and DI (P<0.05). Network pharmacology identified 151 potential therapeutic targets for ZSWQF against COPD, with key nodes including TNF, IL-6, protein kinase B (Akt) 1, albumin (ALB), tumor protein p53 (TP53), non-receptor tyrosine kinase (SRC), epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 3 (STAT) 3, matrix metalloproteinase (MMP)-9, and beta-catenin (CTNNB1). Enrichment analysis indicates involvement of cancer-related, phosphatidylinositol 3-kinase (PI3K)/Akt, hypoxia-inducible factor (HIF)-1, calcium, and MAPK signaling pathways. Western blotting results showed that compared with the LPS group, AEC II treated with ZSWQF-containing serum exhibited decreased expression of ACE, p-p38/p38, p-ERK1/2/ERK1/2, p-JNK/JNK, p-IκBα/IκBα, and p-NF-κBp65, while ACE2 expression was upregulated, consistent with the MAPK/nuclear factor-kappa B (NF-κB) pathway regulation predicted by network pharmacology.
CONCLUSIONS
Aerosolized ZSWQF provides protective effects in COPD mice by reducing airway inflammation and remodeling.
Animals
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Pulmonary Disease, Chronic Obstructive/etiology*
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Drugs, Chinese Herbal/therapeutic use*
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Mice
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Mice, Inbred C57BL
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Male
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Network Pharmacology
;
Smoke/adverse effects*
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Bronchoalveolar Lavage Fluid
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Administration, Inhalation
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Inflammation/drug therapy*
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Tumor Necrosis Factor-alpha
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Lung/drug effects*
;
Interleukin-6/blood*
7.Schistosoma japonicum cystatin has protective effects against "two-hit" sepsis in mice by regulating the inflammatory microenvironment.
Wenjuan DUO ; Yixiang WANG ; Jiaxing WANG ; Xinlong XU ; Linxian LI ; Dongchen YANG ; Qili SHEN ; Lichun YANG ; Xiaojing LIU ; Qiwang JING ; Liang CHU ; Xiaodi YANG
Journal of Southern Medical University 2025;45(1):110-117
OBJECTIVES:
To evaluate the protective effect of Schistosoma japonicum cystatin (rSj-Cystatin) in a mouse mode of "two-hit" sepsis.
METHODS:
Sixty male C57BL/6 mice randomized equally into sham-operated group, protein group, "two-hit" modeling group, and protein intervention group. In the former two groups, the mice received an intraperitoneal injection of 100 μL PBS followed by exposure of the cecum and then by intraperitoneal injection of 100 μL PBS or 25 μg rSj-Cystatin 30 min later; In the latter two groups, 100 μL PBS containing LPS (5 mg/kg) was injected intraperitoneally 24 h before cecal ligation and puncture (CLP), and 100 μL PBS or 25 μg rSj-Cystatin were injected 30 min after CLP. At 12 h after rSj-Cystatin treatment, 6 mice from each group were sacrificed for detection of TNF-α, IL-6, IL-10, TGF-β, iNOS and Arg-1 in the serum, spleen, liver, lung and kidney tissues using ELISA, for examinations of liver, lung and kidney pathologies with HE staining, and for analysis of CD3+CD4+CD25+Foxp3+ T cell percentage in the spleen using flow cytometry. The remaining mice were observed for general condition and 72-h survival.
RESULTS:
The 72-h survival rates in the 4 groups were 100%, 100%, 0% and 20%, respectively, showing significant differences between the latter two groups. The mouse models of "two-hit" sepsis exhibited obvious tissue pathologies and significant elevations of TNF-α and IL-6 in both the serum and tissue homogenate, which were significantly ameliorated by rSj-Cystatin treatment. Treatment with rSj-Cystatin also increased IL-10 and TGF-β levels and spleen CD3+CD4+CD25+Foxp3+ T cell percentage. The septic mouse models also showed increased iNOS levels in all the detected tissues and a decreased Arg-1 level in the kidney, and these changes were obviously improved by rSj-Cystatin treatment.
CONCLUSIONS
rSj-Cystatin has a protective effect against "two-hit" sepsis in mice by regulating the inflammatory microenvironment.
Animals
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Mice
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Sepsis/drug therapy*
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Male
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Schistosoma japonicum/chemistry*
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Mice, Inbred C57BL
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Cystatins/therapeutic use*
;
Interleukin-10/metabolism*
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Interleukin-6/blood*
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Tumor Necrosis Factor-alpha/blood*
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Disease Models, Animal
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Transforming Growth Factor beta/metabolism*
8.Effect of ginsenoside Rb3 on experimental periodontitis in rats.
Hua LI ; Kang ZHANG ; Huijuan QU ; Honghai JI ; Minmin SUN
West China Journal of Stomatology 2025;43(5):711-721
OBJECTIVES:
This study aimed to explore the therapeutic effect and mechanism of ginsenoside Rb3 on experimental periodontitis and bone resorption in rats.
METHODS:
Male SD rats were randomly divided into a control group, a ligation group, an Rb3 group, and a doxycycline (Dox) group for in vivo experiments. A periodontitis model was established by ligating the maxillary second molar, and samples were collected after 3 weeks of drug treatment. Micro-CT assessment of alveolar bone resorption was performed, and hematoxylin-eosin (HE) staining was used to observe pathological changes in periodontal and visceral tissues. Tartrate resistant acid phosphatase (TRAP) staining was applied to detect the formation of osteoclasts in periodontal tissues, and enzyme-linked immunosorbent assay (ELISA) was adopted to detect the serum levels of interleukin (IL)-6, IL-8, immunoglobulin (Ig)M, and IgG. Quantitative polymerase chain reaction (qPCR) was employed to detect the expression of factors related to gingival inflammation and osteoclast formation. Immunofluorescence staining was used to detect phospho-extracellular signal-regulated kinase (p-ERK) expression. In vitro experiments were conducted by pretreating RAW264.7 cells with drugs and adding lipopolysaccharides (LPS) stimulation from Porphyromonas gingivalis (P. gingivalis). IL-1β and IL-6 mRNA expression was detected by qPCR, and Western blot was used to detect the effect of Rb3 on the mitogen-activated protein kinases (MAPKs) signaling pathway.
RESULTS:
Compared with the control group, the ligation group showed significant periodontitis and bone resorption. Compared with the ligation group, the Rb3 group showed a decrease in alveolar bone resorption and osteoclast formation; p-ERK/ERK ratio, IL-1β, IL-6, and nuclear factor of activated T cells (NFATc1) mRNA levels and downstream gene expression in periodontal tissues; serum IL-6, IL-8, IgG, and IgM levels. Rb3 reduced IL-8 and IL-1β mRNA expression levels and p-ERK/ERK and p-p38 MAPK/p38 MAPK ratios in RAW264.7 cells induced by P. gingivalis LPS stimulation.
CONCLUSIONS
Rb3 inhibits inflammation and bone resorption in experimental periodontitis in rats. Compared with Dox, Rb3 has better effects in inhibiting pro-inflammatory factors and osteoclast gene expression and may exert anti-inflammatory effects by activating the MAPK signaling pathway.
Animals
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Ginsenosides/therapeutic use*
;
Rats, Sprague-Dawley
;
Male
;
Periodontitis/pathology*
;
Rats
;
Osteoclasts/drug effects*
;
Interleukin-1beta/metabolism*
;
Interleukin-6/blood*
;
Mice
;
Alveolar Bone Loss
;
Interleukin-8/blood*
;
Immunoglobulin G/blood*
;
RAW 264.7 Cells
;
Transcription Factors
9.Liangxue Jiedu Huayu Formula improves liver function of mice with acute-on-chronic liver failure by inhibiting excessive activation of the cGAS-STING signaling pathway.
Qiao TANG ; Chao ZHOU ; Zhaofang BAI ; Qing YAO ; Simin CHEN ; Xinru WEN ; Zhaoyun HE ; Jin ZHANG ; Ruisheng LI ; Man GONG
Journal of Southern Medical University 2024;44(12):2291-2299
OBJECTIVES:
To explore the role of the cGAS-STING signaling pathway in the therapeutic mechanism of Liangxue Jiedu Huayu Formula (LXJDHYF) for acute-on-chronic liver failure (ACLF) in mice.
METHODS:
Thirty C57BL/6 mice were randomly divided into blank control group, model group, low- and high-dose LXJDHYF groups, and H151 (a specific cGAS-STING pathway inhibitor) group (n=6). In all but the control group, the mice were treated with CCl4 to induce liver cirrhosis followed by intraperitoneal injections of lipopolysaccharide and D-amino galactose to establish mouse models of ACLF. After the treatments, the mouse livers were collected for HE and TUNEL staining, and serum levels of ALT, AST and TBil were determined. In bone marrow-derived macrophages (BMDMs) and liver tissues of ACLF mice, the expressions of cGAS-STING signaling pathway-related mRNAs including IFN‑β, ISG15, IL-6 and TNF-α were determined with RT-qPCR, and the phosphorylation levels of IRF3 and STING proteins were investigated using Western blotting.
RESULTS:
Compared with the mice in the model group, the LXJDHYF-treated mice exhibited milder hepatocyte necrosis and inflammatory cell infiltration in the liver with significantly reduced hepatocyte apoptosis. LXJDHYF treatment also significantly lowered serum levels of ALT, AST, TBil, IL-6 and TNF-α in ACLF mice and effectively suppressed the expressions of cGAS-STING signaling pathway-related mRNA in both the BMDMs and the liver tissues and the phosphorylation of IRF3 and STING proteins in the BMDMs.
CONCLUSIONS
LXJDHYF can significantly improve liver function and attenuate inflammation in ACLF mice possibly by inhibiting excessive activation of the cGAS-STING signaling pathway.
Animals
;
Signal Transduction/drug effects*
;
Mice
;
Nucleotidyltransferases/metabolism*
;
Mice, Inbred C57BL
;
Acute-On-Chronic Liver Failure/etiology*
;
Membrane Proteins/metabolism*
;
Drugs, Chinese Herbal/therapeutic use*
;
Liver/metabolism*
;
Disease Models, Animal
;
Interferon Regulatory Factor-3/metabolism*
;
Interleukin-6/metabolism*
;
Male
10.Clinical efficacy of vitamin B1 in ICU-acquired weakness patients.
Dandan ZHOU ; Jianhua GUO ; Xuebin WANG
Chinese Critical Care Medicine 2024;36(12):1301-1304
OBJECTIVE:
To observe the clinical efficacy of vitamin B1 in patients with ICU-acquired weakness (ICU-AW).
METHODS:
A retrospective analysis was conducted to select ICU-AW patients treated with vitamin B1 in the intensive care unit (ICU) of Shanghai East Hospital, Tongji University from July 2022 to December 2023. Propensity score matching was used to match the control group and observation group at a 1 : 1 ratio, considering differences in patient age, gender, and acute physiology and chronic health evaluation II (APACHE II). The control group received conventional treatment, while the observation group received vitamin B1 in addition to conventional treatment. Comparisons were made between the two groups in terms of basic information, APACHE II scores, Medical Research Council muscle strength score (MRC), interleukin-6 (IL-6), C-reactive protein (CRP), and serum creatinine (SCr) levels before and after treatment, mechanical ventilation time, and length of ICU stay were collected and compared between the two groups.
RESULTS:
A total of 30 patients with ICU-AW were included, both 15 in each group. There were no significant differences in gender, age and APACHE II score between the two groups. There were no significant differences in APACHE II score, MRC score, IL-6, CRP, SCr levels, and the duration of ventilator-assisted ventilation and ICU stay between the two groups of patients before treatment. Both groups showed improvements in APACHE II scores and MRC scores after treatment, with the observation group showing significantly greater improvement compared to the control group (APACHE II score: 10.80±1.47 vs. 12.20±1.52, MRC score: 50.40±7.10 vs. 42.00±8.78, both P < 0.05). After treatment, both groups showed significant reductions in IL-6, CRP, and SCr levels, but there were no significant differences between the observation group and control group. The observation group had significantly shorter durations of mechanical ventilation (days: 7.67±1.54 vs. 9.67±2.44, P < 0.05) and ICU stay (days: 13.33±1.72 vs. 15.13±2.56, P < 0.05) compared to the control group.
CONCLUSIONS
The use of vitamin B1 during the treatment of ICU-AW significantly improves muscle strength and reduces the duration of mechanical ventilation and ICU stay.
Humans
;
Intensive Care Units
;
Retrospective Studies
;
APACHE
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Muscle Weakness/drug therapy*
;
Respiration, Artificial
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Thiamine/therapeutic use*
;
C-Reactive Protein
;
Interleukin-6/blood*
;
Length of Stay
;
Male
;
Female
;
Treatment Outcome
;
Propensity Score
;
Middle Aged

Result Analysis
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