Background Exposures to environmental pollution and specific occupational hazards exacerbate pulmonary fibrosis which has a complex pathogenesis and lacks effective therapeutic drugs. The extract from Dracocephalum moldavica L. can alleviate pulmonary fibrosis through anti-inflammatory and anti-pyroptosis pathways, but its mechanism of prevention and treatment for pulmonary fibrosis remains unclear. Objective To elucidate the targets and potential mechanism underlying the anti-pulmonary fibrosis efficacy of Dracocephalum moldavica L. extract by employing an amalgamation of network pharmacology and empirical verification. Methods The chemical composition of the extract of Dracocephalum moldavica L. was retrieved with the help of China National Knowledge Infrastructure (CNKI) and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The disease targets related to pulmonary fibrosis were inquired using Gene Cards and DisGeNET. A protein-protein interaction (PPI) was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) database and Cytoscape software. The predicted potential targets were analyzed by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses through the Database for Annotation, Visualization and Integrated Discovery (DAVID) and validated by molecular docking. Thirty-two rats were randomly divided into a control group, a model group, a low-dose group of Dracocephalum moldavica L. extract (100 mg·kg⁻¹), and a high-dose group of Dracocephalum moldavica L. extract (400 mg·kg⁻¹), with eight rats in each group. A rat model of pulmonary fibrosis was constructed using bleomycin (5 mg·kg⁻¹) intratracheal instillation, and an equal volume of saline was instilled into the control group. After modelling, 400 and 100 mg·kg⁻¹ of Dracocephalum moldavica L. extract were given the high-dose and low-dose groups by gavage, and an equal volume of saline was given by gavage to the control group and the model group, once per day, for consecutive 28 d. The animals were then neutralized, and lung tissues were collected. Structural changes in rat lung tissue were evaluated by observing stained pathological sections. Western blot (WB) was used to detect fibrosis-related proteins type I collagen (Col-I), α-smooth muscle actin (α-SMA), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT) in lung tissues. Real-time fluorescence quantitative PCR (RT-qPCR) was used to detect α-SMA and Col-I mRNA levels in lung tissue. Enzyme-linked immunosorbent assay (ELISA) was used to detect tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in rats. Results A total of 378 key chemical components of the Dracocephalum moldavica L. extract and 1611 lung fibrosis-related targets were identified. Among them, 574 potential targets of Dracocephalum moldavica L. extract acting on lung fibrosis were obtained. The key targets determined by Degree value were albumin (ALB), tumour necrosis factor (TNF), AKT1, etc. The results of KEGG analysis suggested that the potential targets of Dracocephalum moldavica L. extract against pulmonary fibrosis mainly involved the PI3K-AKT, HIF-1 signaling pathway, TNF signaling pathway, and MAPK signaling pathway. The molecular docking results showed that the binding energy between the active components (quercetin, apigenin, aesculetin, quercitrin) of Dracocephalum moldavica L. extract and the core targets of pulmonary fibrosis (TNF, IL-6, ALB, AKT1) were all <-29.288 kJ·mol⁻¹, indicating good binding ability. The animal validation results showed that compared with the control group, the rats in the model group had disrupted alveolar structure, obvious inflammatory cell infiltration, positive blue-striped collagen fibre deposition, and increased Col-I and α-SMA protein expression and transcription levels (P<0.001), p-PI3K and p-AKT expression levels (P<0.001), and levels of inflammatory factors TNF-α, IL-6, and IL-1β (P<0.001). Compared with the model group, the high- and low-dose groups of Dracocephalum moldavica L. extract alleviated the progression of pulmonary fibrosis, reduced inflammatory cell infiltration, and attenuated collagen fibre deposition in rats, with a decrease in the protein expression and transcription levels of Col-I and α-SMA (P<0.01), the expression levels of p-PI3K and p-AKT (P<0.001), and the levels of inflammatory factors IL-6 and TNF-α (P<0.05, P<0.001). Conclusion Dracocephalum moldavica L. extract manifests anti-pulmonary fibrotic properties through the modulation of the PI3K-AKT signaling cascade and the suppression of inflammatory reactions.

Objective:To investigate the expression of KCTD8 gene in breast ductal carcinoma and its correlation with clinical factors and prognosis.Methods:Immunohistochemistry technology(IHC)were employed to detect protein expression levels of KCTD8 in 27 pairs of breast ductal carci-noma and its paired adjacent tissues.Analyzing the correlation between changes in KCTD8 expres-sion of protein and clinical factors using statistical techniques.RNA expression and methylation data of breast cancer(including intraductal cancer)were analysed from TCGA database.Result:The pro-tein expression of KCTD8 gene in 27 pairs of breast ductal carcinoma tissues showed a decreasing trend compared to adjacent tissues(P＜0.05),and the decreased expression level of protein was cor-related with the tumor size of patients(P＜0.05).The analysis results of the TCGA database indicate that the expression and hypemethylation of KCTD 8 gene in breast cancer(including intraductal can-cer)tissues affected the prognosis of patients.Conclusion:The reduced protein expression level of KCTD8 gene in breast ductal carcinoma may be involved in the development and affect the prog-nosis of patients.

Humans ; Vascular Stiffness ; Coal Mining ; Occupational Diseases/epidemiology* ; Risk Factors ; Coal ; Miners

The breakage pattern of unit particles during the production of oral solid dosage forms (OSD) is closely related to the quality of intermediate or final products. To accurately characterize the particles and study the evolution law of particle breakage, the Bonding model of the discrete element method (DEM) was used to investigate the breakage patterns of model parameters, particle shape and process conditions (loading mode and loading rate) on the dynamic breakage, force-time curve, breakage rate, maximum breakage size ratio and fracture strength of particles. The results showed that the particle breakage force was positively correlated with normal strength and bonded disk scale, negatively correlated with normal stiffness per unit area and tangential stiffness per unit area, and weakly correlated with tangential strength. The particle breakage rate was negatively correlated with the aspect ratio of the particles, and the maximum breakage size ratio was positively correlated with the aspect ratio of the particles; among the three loading modes, the breakage rate of compression breakage model was the largest, the breakage rate of shear breakage model was the second largest, and the breakage rate of wear breakage model was the smallest; the maximum breakage size ratio was positively correlated with the loading rate, the loading mode and the loading rate had no mutual influence on particle breakage rate, but had mutual influence on the maximum breakage size ratio. The research results will provide a theoretical basis for the shift of OSD from batch manufacturing to advanced manufacturing.

In recent years, the development of host-acting antibacterial compounds has gradually become a hotspot in the field of anti-infection. Through research on the interaction mechanism between hosts and pathogenic bacteria, it has been found that the immune system is one of the key targets of host-acting antibacterial compounds. There is a communication system called the quorum sensing system in microorganisms, which mainly adjusts the structure of multi-microbial community and coordinates the group behavior. When the quorum sensing molecules secreted by microorganisms reach a threshold concentration, the quorum sensing system is activated and the overall gene expression of the microorganism is changed. In addition to regulating the density of microorganisms, quorum sensing molecules can also act as a link between pathogenic microorganisms and hosts, entering the host immune system and playing a role in affecting the morphological structure of immune cells, secreting cytokines, and inducing apoptosis, leading to host immune injury and causing host immune dysfunction.The key mechanism of 3-oxo-C12-HSL and other acyl-homoserine lactone (AHL) molecules in the innate immune system has been extensively studied. The lipid solubility allows AHLs to pass through the plasma membrane of host immune cells easily and induce dissolution of lipid domains. Then, it acts through signaling pathways such as p38MAPK and JAK-STAT, further influencing the immune cell’s defense response to bacteria and potentially leading to cell apoptosis. Additionally, the human lactonase paraoxonase 2, which can degrade3-oxo-C12-HSL, has been found in macrophage. It acts as an immune regulator that promotes macrophage phagocytosis of pathogens and is hypothesized to have the ability to reduce bacterial resistance. The mechanism of quorum sensing molecules in the adaptive immune system is less studied, the current results suggest that 3-oxo-C12-HSL is closely related to the mitochondrial pathway in host immune cells. For example, 3-oxo-C12-HSL induces apoptosis of Jurkat cells by inhibiting the expression of three mitochondrial electron transport chain proteins; it can also trigger mitochondrial dysfunction and induce mast cell apoptosis through Ca²⁺ signaling.Among the quorum sensing molecules, the AHLs have the greatest impact on plant immune system. The different effects on plant resistance depends on the chain lengths of acyl groups in bacterial-produced AHLs. Short-chain AHLs (C4-HSL and C8-HSL) induce plant resistance to pathogenic bacteria mainly through the auxin pathway and jasmonic acid pathway. Long-chain AHL (3-oxo-C14-HSL) is commonly used in hosts against fungal pathogens by inducing stomata defense responses, and the reaction process is related to salicylic acid. Diffusible signal factor molecules also interfere with the stomatal immunity caused by pathogens. It may act through the formin nanoclustering-mediated actin assembly and MPK3 pathway to inhibit the innate immunity of Arabidopsis. In summary, AHLs induced different plant pathways and affects the plant-bacteria interactions to trigger plant immunity. As a quorum sensing molecule of fungi, farnesol has similar effects on host immunity as AHLs, such as stimulating cytokine secretion and activating an inflammatory response. It also plays a unique role on dendritic cell differentiation and maturation. In addition, studies have found that farnesol has a protective effect on autoimmune encephalomyelitis, which may be related to its effect on the composition of intestinal microorganisms of the host.Therefore, targeting the host immune system and quorum sensing molecules to develop antibacterial compounds can effectively inhibit the invasion of pathogens and subserve the host to resist the influence of pathogenic bacteria. This article will review the mechanism of host immune responses triggered by important quorum sensing molecules, aiming to explore the targets of host-acting antibacterial compounds and provide new directions for the prevention or treatment of causative infectious sources and the development of related drugs.

G protein-coupled receptor (GPR) 40, as one of GPRs family, plays a potential role in regulating glucose and lipid metabolism. To study the effect of GPR40 novel agonist SZZ15-11 on hyperglycemia and hyperlipidemia and its potential mechanism, spontaneous type 2 diabetic KKA^y mice, human hepatocellular carcinoma HepG2 cells and murine mature adipocyte 3T3-L1 cells were used. KKA^y mice were divided into four groups, vehicle group, TAK group, SZZ (50 mg·kg^-1) group and SZZ (100 mg·kg^-1) group, with oral gavage of 0.5% sodium carboxymethylcellulose (CMC), 50 mg·kg^-1 TAK875, 50 and 100 mg·kg^-1 SZZ15-11 respectively for 45 days. Fasting blood glucose, blood triglyceride (TG) and total cholesterol (TC), non-fasting blood glucose were tested. Oral glucose tolerance test and insulin tolerance test were executed. Blood insulin and glucagon were measured via enzyme-linked immunosorbent assay (ELISA). After mice′s execution, liver tissue was harvested to test TG and TC content. Then pathological morphology of liver was observed through hematoxylin-eosin (HE) staining, and the lipid metabolism relative signal pathway was analyzed by Western blot and RT-PCR. The experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College. At the same time, Akt phosphorylation level in HepG2 cells and adiponectin in 3T3-L1 cells treated with TNFα were measured with Western blot. The results show that SZZ15-11 not only decreased blood glucose and lipid, improved insulin sensitivity, but also increased fasting blood glucagon and promoted insulin secretion after glucose loading in KKA^y mice. Additionally, SZZ15-11 alleviated hepatic steatosis and liver dysfunction in KKA^y mice. In liver tissue, SZZ15-11 increased AMPKα phosphorylation level and cholesterol metabolism relative gene Abcg8 transcription. In HepG2 cells, SZZ15-11 increased Akt phosphorylation level. In adipocyte 3T3-L1, SZZ15-11 recovered the decreased adiponectin expression by TNFα. This study proved that GPR40 agonist SZZ15-11 could be a candidate compound for regulating glucolipid metabolic disorder.

The effect of different concentrations of glycyrrhizic acid (GA) and Zn²⁺ on the self-assembly of metal complexes was investigated by forming metal complexes, and the properties and assembly mechanisms of the formed carrier-free supramolecular hydrogel were characterised. Scanning electron microscopy (SEM) and zeta potential were used to characterise the microscopic morphology and stability of the GA-Zn complex hydrogel, which had spherical-like particles of about 1 μm with good stability; the rheometer was used to detect its materialistic properties, which showed excellent stability, self-healing property and reversibility; through in vitro bacterial inhibition, it was found that the GA-Zn carrier-free supramolecular hydrogel has enhanced bacterial inhibition function after assembly. The hydrogel was also found to possess both anti-inflammatory and antioxidant efficacy when evaluated using LPS and H₂O₂ induced RAW 264.7 cell damage models, respectively. The above results suggest that GA-Zn hydrogel not only has good materialistic properties, but also possesses good antibacterial, anti-inflammatory and antioxidant activities, which has the value of clinical research as a carrier-free multi-functional antimicrobial dressing, and the present study provides a reference for the discovery of novel biomedical materials from active molecules of natural traditional Chinese medicine.

Twelve compounds were isolated from the ethyl acetate fraction of the 80% aqueous ethanol extract of the roots and stems of Dalbergia rimosa Roxb. by silica gel, MCI, Sephadex LH-20 column chromatography, and semi-preparative HPLC. Their structures were identified by spectral analysis such as UV, IR, MS, 1D/2D NMR and by comparison with literature information as dalbergiquinol A (1), dalbergiquinol B (2), R-(-)-3′-hydroxy-2,4,5-trimethoxydalbergiquinol (3), neokhriol A (4), mucronulatol (5), (3R)-7,2′,3′-trihydroxy-4′-methoxy-isoflavane (6), isomucronulatol (7), (3S)-violanone (8), 3′-O-methylviolanone (9), eryvarin M (10), (±)-α,3,4,2′,4′-pentahydroxydihydrochalcone (11) and (-)-butin (12). Compound 1 and 2 are new compounds, and compounds 3-12 were isolated from this plant for the first time. Compounds 1, 2, 4, 6, 8, 11, 12 showed good scavenging effect on DPPH free radical.

Based on the interaction between supramolecule of traditional Chinese medicine and enterobacteria, the material basis of Rhei Radix et Rhizoma and Coptidis Rhizoma was explored. Scanning electron microscopy (SEM) and dynamic light scattering (DLS) were used to characterize the morphological differences of Rhubarb single decoction, Coptis single decoction and Rhubarb and Coptis co-decoction. An in vitro antibacterial model (E. coli, E. faecium and B. subtilis) was established to evaluate the damage effect of the combination of Rhei Radix et Rhizoma and Coptidis Rhizoma on enterobacteria. Ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to analyze the changes of chemical components of single decoctions and co-decoctions. The co-decoction of Rhei Radix et Rhizoma and Coptidis Rhizoma was turbid after decocting. The spherical particles of 300-400 nm were observed under SEM, and the co-decoction was more uniform and stable than that of single decoction. The interaction between supramolecules formed after the combination of Rhei Radix et Rhizoma and Coptidis Rhizoma and enterobacteria was significantly different from that of single decoction. In the process of interaction between supramolecules and enterobacteria, the spherical state was maintained, and the medicinal ingredients in Coptidis Rhizoma or Rhei Radix et Rhizoma were blocked, which could effectively alleviate the damage to enterobacteria. This study provided a reference for subsequent studies on the regulation of intestinal flora homeostasis by the combination of Rhei Radix et Rhizoma and Coptidis Rhizoma.

Objective To observe the clinical efficacy of acupuncture combined with Guanxinning Tablets in the treatment of heart vessel obstruction type of chest obstruction syndrome.Methods Eighty patients with heart vessel obstruction type of chest obstruction syndrome were randomly divided into the observation group and the control group,with 40 cases in each group,the control group was given conventional western medicine treatment,the observation group was given acupuncture combined with Guanxinning Tablets on the basis of the treatment in the control group,and the patients in the two groups were treated continuously for 30 days.The clinical efficacy of the two groups was evaluated after 1 month of treatment.After 1 month of treatment,the clinical efficacy of the two groups was evaluated.The changes in the traditional Chinese medicine(TCM)scores,including chest tightness,palpitations,stabbing pains in the chest,and dark complexion,as well as the frequency and duration of angina pectoris were observed before and after the treatment in the two groups.The changes of serum monocyte chemotactic factor 1(MPC-1),hs-CRP,tumor necrosis factor α(TNF-α),mitogen-activated protein kinase(MAPK),and Toll-like receptor 4(TLR4)were observed before and after treatment in the two groups.Results(1)The total effective rate was 95.00%(38/40)in the observation group and 75.00%(30/40)in the control group.The efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the TCM syndrome scores of patients in the two groups,including chest tightness and palpitations,chest tingling,and dark complexion,were significantly improved,and the observation group was significantly superior to the control group in improving the TCM syndrome scores of chest tightness and palpitations,chest tingling,and dark complexion,and the difference was statistically significant(P＜0.05).(3)After treatment,the frequency and duration of angina attacks in the two groups were significantly improved,and the observation group was significantly superior to the control group in improving the frequency and duration of angina attacks,and the difference was statistically significant(P＜0.05).(4)After treatment,the serum hs-CRP,MPC-1,and TNF-α levels of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the serum hs-CRP,MPC-1 and TNF-α levels,and the difference was statistically significant(P＜0.05).(5)After treatment,the serum MAPK and TLR4 levels of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving serum MAPK and TLR4 levels,and the difference was statistically significant(P＜0.05).Conclusion Acupuncture combined with Guanxinning Tablets for the treatment of heart vessel obstruction type of chest obstruction syndrome can significantly improve the clinical symptoms of the patients,effectively alleviate the body's inflammatory response,reduce the level of serum MAPK and TLR4,and the clinical efficacy is remarkable.