Aim To investigate the effect of colchicine on lipopolysaccharide (LPS) induced endothelial to mesenchymal transition (EndMT) in human umbilical vein vascular endothelial cells (HUVECs) and its related mechanisms. Methods The EndMT model was established by treating HUVECs with LPS. Cell proliferation rate was detected by CCK-8 assay, cytotoxicity was detected by LDH assay, and the optimal drug concentration was screened. The cells were divided into the normal control group, the normal control + colchicine (10 nmol • L) group, the LPS (10 mg • L) model group, and the LPS + colchicine (10 nmol • L) group. The morphologic changes of the cells were observed under an inverted microscope, the cell migration ability was detected by Transwell assay, and the ability of tube formation was analyzed by tube formation assay. The expression of endothelial markers (CD31/ VE-cadherin) and mesenchymal cell markers (a-SMA/FSP-1) were detected by Western blot. NF-KB inhibitor was used to detect the changes in related signaling pathways. Results CCK-8 and LDH experiments showed that 10 nmol • L colchicine was the optimal concentration. LPS could induce morphological changes in HUVECs, and colchicine could reverse morphological changes in HUVECs to a certain extent. Transwell experiment showed that the migration ability of HUVECs in the LPS treatment group was significantly enhanced (P < 0. 05), and colchicine could significantly reverse this phenomenon (P < 0. 05) . Tube formation experiment showed that LPS decreased the endothelial tube formation ability of HUVECs (P < 0. 05), while colchicine treatment markedly improved LPS-induced tube formation defects (P < 0. 05) . Western blot assay showed that after colchicine co-cultured with LPS, the expression levels of CD31 and VE-cadherin significantly increased compared with the model group (P < 0. 05), while the expression levels of a-SMA and FSP-1 significantly decreased compared with the model group (P < 0. 05) . During the induction of EndMT by LPS, colchicine could inhibit the activation of the NF-KB/Snail signaling pathway. Conclusions Colchicine can effectively inhibit EndMT induced by LPS, and the mechanism may be related to the regulation of the NF-KB/Snail signaling pathway.

Objective:To explore the application effect of the single-port air-filling technique in breast-conserving surgery for patients with early breast cancer.Methods:A retrospective study was conducted to select 60 female patients with early breast cancer who underwent breast-conserving surgery in the Beijing Fengtai Hospital from June 2020 to June 2023, and they were divided into two groups according to different surgical methods: observation group ( n=28) and control group ( n=32). Patients in the observation group were treated with single-port air-filling technique in breast-conserving surgery, while patients in the control group were treated with traditional open breast-conserving surgery. Perioperative indicators of the two groups of patients were analyzed, including operation time, intraoperative bleeding volume, postoperative drainage time, postoperative drainage volume, postoperative complications, Functional Assessment of Cancer Therapy-Breast (FACT-B) score, tumor recurrence, cosmetic effect and other related indicators. The measurement data were expressed as mean ± standard deviation ( ± s), and independent sample t-test was used for comparison between groups; the count data were expressed as the number of cases and percentage, and the Chi-square test was used for comparison between groups. Results:All 60 patients had successfully completed the surgery. The operative time in the observation group was (123.6±35.2) min, which was significantly longer than that in the control group [(62.3±21.5 ) min], and the difference was statistically significant ( P<0.05). The intraoperative bleeding volume in the observation group was (21.2±12.3) ml, which was significantly lower than that in the control group [(38.3±18.6) mL], and the differences were statistically significant ( P< 0.05). The postoperative drainage time and drainage volume between the two groups of patients has no statistically significant difference ( P>0.05). There was no skin necrosis and wound infection in both groups. In terms of cosmetic effect scores at 1 and 6 months after surgery, the observation group [(10.8±0.8), (11.6±1.3) points] were superior to the control group [(8.9±0.9), (9.2±1.2) points], and the differences were statistically significant ( P<0.05). In terms of postoperative FACT-B score at 1 and 6 months after surgery, the observation group [(15.40±2.00), (18.60±2.10) points] were higher than control group [(11.10±2.90), (17.10±2.70) points], and the differences were statistically significant ( P<0.05). There was no local recurrence or distant metastasis in both groups during the follow-up period. Conclusion:The application of single-port air-filling technique in breast-conserving surgery for patients with early breast cancer not only has a definite tumor treatment effect, but also has ideal cosmetic effect, which greatly improves the quality of life of patients.

This study established a pyroptosis injury model by stimulating insulinoma cells(INS-1) of rats with high glucose(HG) and observed the impact of additional ethanol(ET) exposure on cell pyroptosis, as well as the intervention effect of salidroside(SAL). INS-1 cells were cultured and divided into a normal control group(NG), an HG group, an HG + ET(100 mmol·L~(-1)) group, and an HG + ET + SAL(1-100 μmol·L~(-1)) group. After 72 hours of treatment, cell viability was assessed using the cell counting kit-8(CCK-8) assay. The number of pyroptotic bodies was observed under a microscope. Western blot was used to detect changes in the intracellular Nod-like receptor protein 3(NLRP3)/gasdermin D(GSDMD) signaling pathway and adenosine monophosphate-activated protein kinase(AMPK) activity. A fluorescence probe was used to detect changes in intracellular reactive oxygen species(ROS) levels. Time-resolved fluorescence resonance energy transfer(TR-FRET) technology was employed to observe the effect of SAL on recombinant AMPK protein kinase activity in vitro. The results showed that compared to the NG group, HG exposure induced an increase in the number of pyroptotic bodies, elevated ROS levels, and activation of the NLRP3/GSDMD signaling pathway in INS-1 cells. Compared to the HG group, HG + ET exposure further exacerbated these changes. Compared to the HG + ET group, SAL dose-dependently increased cell viability, reduced the formation of pyroptotic bodies in INS-1 cells, and inhibited excessive ROS production, overactivation of the NLRP3/GSDMD signaling pathway, and the decrease in AMPK activity. TR-FRET experiments indicated that SAL could directly activate AMPK. When INS-1 cells were pretreated with an AMPK inhibitor, the effects of SAL on increasing cell viability, alleviating the formation of pyroptotic bodies, and inhibiting excessive ROS production were abolished. These results suggest that SAL can alleviate HG combined with ET-induced exacerbation of INS-1 pyroptosis by activating AMPK.
Pyroptosis/drug effects* ; Animals ; Rats ; Glucose/metabolism* ; Insulinoma/metabolism* ; Ethanol/pharmacology* ; Reactive Oxygen Species/metabolism* ; Glucosides/pharmacology* ; Phenols/pharmacology* ; Cell Line, Tumor ; Signal Transduction/drug effects* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Cell Survival/drug effects* ; AMP-Activated Protein Kinases/metabolism* ; Phosphate-Binding Proteins/genetics*

This study aimed to explore the anti-glioma effect of natural compound pterostilbene(PTE) through regulating pyroptosis and apoptosis pathways, and to analyze the possible anti-glioma pathways and targets of PTE by network pharmacology and molecular docking. In this study, the action targets of PTE and the glioma targets were obtained by network pharmacology to construct a target network and a protein-protein interaction(PPI) network to predict the possible action targets of PTE against glioma. Molecular docking was performed on the core targets by AutoDock and the action pathways of PTE against glioma were predicted by enrichment analysis. In addition, the effect of PTE on the viability of U87MG and GL261 glioma cells was detected by CCK-8 assay. Clone formation assay and cell scratching assay were used to explore the effect of different concentrations of PTE on the proliferation and migration, respectively of glioma cells. Hoechst staining was used to observe PTE-induced apoptosis in glioma cells. The changes in mitochondrial membrane potential were detected by JC-1 staining. The pyroptosis-inducing effect of PTE on glioma cells was observed by inverted microscopy and lactate dehydrogenase(LDH) assay. Hoechst 33342/PI dual staining assay was performed to detect the integrity of glioma cell membranes. The expressions of pyroptosis and apoptosis-related proteins in glioma cells after PTE induction were determined by Western blot. In this study, 37 anti-glioma targets of PTE were obtained, and enrichment analysis suggested that PTE exerted anti-glioma effects through various signaling pathways including cancer pathway, proteoglycan in cancer, PI3K/AKT pathway, and apoptosis regulatory pathway. Molecular docking revealed that PTE had good binding activity with the main targets. Compared with the control group, PTE significantly reduced the viability as well as the proliferation, migration and adhesion abilities of U87MG and GL261 cells; it induced the apoptosis of the two glioma cells and the decrease of mitochondrial membrane potential in U87MG cells, and the effects increased with the increase of drug concentration. Compared with the conditions in the control group, glioma cells in the PTE group had increased pyroptosis-specific appearance and gradually increased LDH release; the number of PI positive cells was significantly elevated with the increase of PTE concentration as revealed by Hoechst 33342/PI staining; the expression levels of apoptosis-related factors cleaved PARP1 and B-cell lymphoma-2(Bcl-2) associated X(BAX) in the PTE group were markedly up-regulated, while the expression level of Bcl-2 was markedly down-regulated; the activation levels of pyroptosis-related proteins cleaved caspase-3 and gasdermin E-N(GSDME-N) had a remarkable rise in the PTE group, while no significant changes were found in the activation levels of gasdermin D-N(GSDMD-N) and cleaved caspase-1. In summary, PTE plays an anti-glioma role by inhibiting cell viability, proliferation, and migration and activating the caspase-3/GSDME-mediated pyroptosis pathway and mitochondrial apoptosis pathway.
Pyroptosis ; Caspase 3/metabolism* ; Network Pharmacology ; Gasdermins ; Molecular Docking Simulation ; Phosphatidylinositol 3-Kinases/metabolism* ; Apoptosis ; Proto-Oncogene Proteins c-bcl-2/metabolism*

BACKGROUND: Evidence on the relations of the American Heart Association's ideal cardiovascular health (ICH) with mortality in Asians is sparse, and the interaction between behavioral and medical metrics remained unclear. We aimed to fill the gaps. METHODS: A total of 198,164 participants without cancer and cardiovascular disease (CVD) were included from the China Kadoorie Biobank study (2004-2018), Dongfeng-Tongji cohort (2008-2018), and Kailuan study (2006-2019). Four behaviors (i.e., smoking, physical activity, diet, body mass index) and three medical factors (i.e., blood pressure, blood glucose, and blood lipid) were classified into poor, intermediate, and ideal levels (0, 1, and 2 points), which constituted 8-point behavioral, 6-point medical, and 14-point ICH scores. Results of Cox regression from three cohorts were pooled using random-effects models of meta-analysis. RESULTS: During about 2 million person-years, 20,176 deaths were recorded. After controlling for demographic characteristics and alcohol drinking, hazard ratios (95% confidence intervals) comparing ICH scores of 10-14 vs. 0-6 were 0.52 (0.41-0.67), 0.44 (0.37-0.53), 0.54 (0.45-0.66), and 0.86 (0.64-1.14) for all-cause, CVD, respiratory, and cancer mortality. A higher behavioral or medical score was independently associated with lower all-cause and CVD mortality among the total population and populations with different levels of behavioral or medical health equally, and no interaction was observed. CONCLUSIONS ICH was associated with lower all-cause, CVD, and respiratory mortality among Chinese adults. Both behavioral and medical health should be improved to prevent premature deaths.
Adult ; Humans ; Cardiovascular Diseases/prevention & control* ; East Asian People ; Prospective Studies ; Risk Factors ; Smoking

Humans ; Nasal Cavity ; Melanoma ; Skin Neoplasms ; Paranasal Sinuses

10,11-Dehydrocurvularin (DCV) is a natural-product macrolide that has been shown to exert anti-inflammatory activity. However, the underlying mechanism of its anti-inflammatory activity remains poorly understood. Aberrant activation of the NLRP3 inflammasome is involved in diverse inflammation-related diseases, which should be controlled. The results showed that DCV specifically inhibited the activation of the NLRP3 inflammasome in association with reduced IL-1β secretion and caspase-1 activation, without effect on the NLRC4 and AIM2 inflammasomes. Furthermore, DCV disturbed the interaction between NEK7 and NLRP3, resulting in the inhibition of NLRP3 inflammasome activation. The C=C double bond of DCV was required for the NLRP3 inflammasome inhibition induced by DCV. Importantly, DCV ameliorated inflammation in vivo through inhibiting the NLRP3 inflammasome. Taken together, our study reveals a novel mechanism by which DCV suppresses inflammation, which indicates the potential role of DCV in NLRP3 inflammasome-driven inflammatory disorders.
Animals ; Mice ; Inflammasomes ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Inflammation/drug therapy* ; Anti-Inflammatory Agents/pharmacology* ; Interleukin-1beta/genetics* ; Mice, Inbred C57BL

Acute lung injury (ALI) is a prevalent and severe clinical condition characterized by inflammatory damage to the lung endothelial and epithelial barriers, resulting in high incidence and mortality rates. Currently, there is a lack of safe and effective drugs for the treatment of ALI. In a previous clinical study, we observed that Jinyinqingre oral liquid (JYQR), a Traditional Chinese Medicine formulation prepared by the Taihe Hospital, Affiliated Hospital of Hubei University of Medicine, exhibited notable efficacy in treating inflammation-related hepatitis and cholecystitis in clinical settings. However, the potential role of JYQR in ALI/acute respiratory distress syndrome (ARDS) and its anti-inflammatory mechanism remains unexplored. Thus, the present study aimed to investigate the therapeutic effects and underlying molecular mechanisms of JYQR in ALI using a mouse model of lipopolysaccharide (LPS)-induced ALI and an in vitro RAW264.7 cell model. JYQR yielded substantial improvements in LPS-induced histological alterations in lung tissues. Additionally, JYQR administration led to a noteworthy reduction in total protein levels within the BALF, a decrease in MPAP, and attenuation of pleural thickness. These findings collectively highlight the remarkable efficacy of JYQR in mitigating the deleterious effects of LPS-induced ALI. Mechanistic investigations revealed that JYQR pretreatment significantly inhibited NF-κB activation and downregulated the expressions of the downstream proteins, namely NLRP3 and GSDMD, as well as proinflammatory cytokine levels in mice and RAW2647 cells. Consequently, JYQR alleviated LPS-induced ALI by inhibiting the NF-κB/NLRP3/GSDMD pathway. JYQR exerts a protective effect against LPS-induced ALI in mice, and its mechanism of action involves the downregulation of the NF-κB/NLRP3/GSDMD inflammatory pathway.
Humans ; NF-kappa B/metabolism* ; Lipopolysaccharides/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Acute Lung Injury/metabolism* ; Lung ; Phosphate-Binding Proteins/therapeutic use* ; Pore Forming Cytotoxic Proteins/therapeutic use*

Pyroptosis， an atypical new cell death mode other than apoptosis and necrosis， has been discovered in recent years. Pyroptosis depends on the cleavage of gasdermins （GSDMs） by Caspases. The activated GSDMs act on the plasma membrane to form a perforation， which results in cell lysis and triggers inflammation and immune response. Pyroptosis can be induced by four distinct signaling pathways， including canonical and non-canonical inflammasome pathways， apoptosis-associated Caspases-mediated pathway， and granzyme pathway. In these signaling pathways， GSDMs are the executors of pyroptosis. Pyroptosis is associated with the death of tumor cells and the inflammatory damage of normal tissues. Recent studies have demonstrated that moderate pyroptosis can lead to tumor cell death to exert an anti-tumor effect， and meanwhile stimulate the tumor immune microenvironment， while it can promote tumor development. Despite the good performance， drug-based anti-tumor therapies such as tumor immunotherapy， chemotherapy， and targeted therapy have some shortcomings such as drug resistance， recurrence， and damage to normal tissues. The latest research shows that a variety of natural compounds have anti-tumor effects in the auxiliary treatment of tumors by mediating the pyroptosis pathways in a multi-target and multi-pathway manner， which provide new ideas for the study of anti-tumor therapy. We reviewed the molecular mechanism of pyroptosis and the regulatory role of pyroptosis in tumors and tumor immune microenvironment， and summarized the recent research progress in the natural medicinal components regulating pyroptosis in anti-tumor therapy， with a view to providing ideas for the research on the anti-tumor therapy based on pyroptosis.

Objective To monitor the indoor radon concentration of urban residents in Shiyan, China, and to analyze the related influencing factors. Methods From April to July, 2019, RSKS standard detectors were used to measure the indoor radon concentration of 125 households in Shiyan, and the results were analyzed. Results The indoor radon concentration of residents in Shiyan showed a skewed distribution, ranging from 13.8 to 145 Bq/m³, and M (P₂₅,P₇₅) was 38.3 (29.0,62.0) Bq/m³. The estimated annual effective dose of radon and radon daughters from inhalation was 0.52-5.50 mSv, and M (P₂₅,P₇₅) was 1.45 (1.10, 2.36) mSv, which was consistent with literature. Building structure (H = 14.10, P < 0.001), floor (H = 24.41, P < 0.001), and geographical region (H = 8.963, P < 0.05) were influencing factors of indoor radon concentration, and the differences were significant. Conclusion The indoor radon concentration of urban residents in Shiyan is lower than the national standard limit. However, in daily life, it is still necessary to take appropriate measures to reduce the concentration of indoor radon as much as possible.