With the widespread use of antimicrobial agents, bacterial drug resistance has become an increasingly severe issue, posing significant challenges to global healthcare. Traditional Chinese medicine (TCM) has emerged as a research focus in the field of bacterial resistance due to its broad sources, high safety profile, low toxicity, and antimicrobial mechanisms distinct from those of chemical drugs. Studies have shown that various TCM herbs, such as Scutellaria baicalensis, exert antibacterial effects through multiple pathways, including disrupting the integrity of bacterial cell walls and membranes, inhibiting nucleic acid and protein synthesis, and impairing energy production and metabolism. Additionally, certain TCM herbs, including Scutellaria baicalensis, Coptis chinensis, and Fritillaria thunbergii, can reverse antimicrobial resistance by eliminating resistant plasmids, inhibiting bacterial efflux pump function, and suppressing β-lactamase activity. TCM holds promising potential for antibacterial applications and synergistically reversing antimicrobial resistance, though systematic analyses remain limited. This review summarizes the mechanisms of antibacterial action of TCM and current research on its synergistic use with antimicrobial agents to reverse drug resistance, aiming to provide insights for developing novel TCM-based antimicrobials and addressing bacterial resistance.

Objective To identify long non-coding RNA (lncRNA) associated with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and investigate their mechanisms. Methods Peripheral blood samples were collected from RA-ILD patients (n＝3), RA patients without lung involvement (n＝3), and healthy controls (n＝3). Next-generation sequencing was performed to screen differentially expressed lncRNA. A human fibrotic lung cell model was established by inducing the MRC-5 cell line with transforming growth factor-β (TGF-β). Following siRNA-mediated knockdown of target genes, changes in inflammatory and oxidative stress-related genes were analyzed via real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Western blotting and dual-luciferase reporter (DLR) assays were used to validate protein expression, ubiquitination levels, and nuclear translocation of oxidative stress regulators, and antioxidant response element (ARE) transcriptional activity. Rescue experiments were conducted to confirm the role of target lncRNA in oxidative stress and inflammation in fibrotic lung cells. Results High-throughput sequencing revealed significant downregulation of LINC00638 in RA-ILD patients. Knockdown of LINC00638 markedly reduced transcriptional levels of interleukin (IL)-4, nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and superoxide dismutase 2 (SOD2), while increasing IL-6, IL-1β, interferon-γ (IFN-γ), and reactive oxygen species (ROS) levels. Furthermore, LINC00638 knockdown decreased Nrf2 protein expression, increased its ubiquitination, reduced nuclear translocation, and suppressed ARE transcriptional activity. In MRC-5 cells, LINC00638 knockdown combined with N-acetylcysteine treatment restored Nrf2 and HO-1 levels while reducing IL-6 expression. Conclusions LINC00638 suppresses inflammatory responses in RA-ILD by activating the Nrf2/ARE antioxidant signaling pathway, suggesting its potential as a therapeutic target for diagnosis and treatment.

OBJECTIVES: To investigate the correlation of PRELID1 with gastric cancer (GC) progression, prognosis, and epithelial-mesenchymal transition (EMT) and the underlying mechanisms. METHODS: We analyzed the data of 115 patients undergoing radical gastrectomy for GC in our hospital between February, 2018 and March, 2023 to explore the correlation of PRELID1 expression level in GC tissues with tumor progression and patient prognosis. In cultured GC cells, the effects of lentivirus-mediated overexpression or interference of PRELID1 were observed on cell migration, invasion and EMT. RESULTS: Immunohistochemical staining revealed significantly higher PRELID1 expression in GC tissues (P<0.001), whose expression level was positively correlated with CEA ≥5 ng/mL (P=0.007), CA199 ≥37 U/mL (P=0.007), G_3-4 stages (P=0.001), T_3-4 stages (P=0.001), and N_2-3 stages (P=0.020). Univariate and Cox multifactorial analysis showed that high PRELID1 level was an independent risk factor affecting 5-year survival of GC patients (P=0.001). In cultured GC cells, PRELID1 overexpression obviously promoted cell proliferation, migration, invasion, and the expressions of MMP2 and MMP9, and interference of PRELID1 produced the opposite changes. PRELID1 overexpression also increased the expressions of N-cadherin and vimentin and reduced the expression of E-cadherin. Mechanistic analyses showed that up-regulation of PRELID1 increased the expression of p-PI3K, p-AKT, and p-mTOR in GC cells, whereas its interference caused the opposite changes; the application of 740 Y-P, a PI3K/AKT pathway activator, significantly enhanced the migration, invasion, and EMT of GC cells with PRELID1 knockdown. CONCLUSIONS PRELID1 is highly expressed in GC and affects prognosis of the patients, and its high expression promotes migration, invasion and epithelial mesenchymal transition of GC cells possibly by activating the PI3K/AKT/mTOR pathway.
Humans ; Stomach Neoplasms/metabolism* ; Epithelial-Mesenchymal Transition ; Prognosis ; Cell Movement ; Cell Line, Tumor ; Male ; Female ; Middle Aged ; Signal Transduction ; Neoplasm Invasiveness ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism*

OBJECTIVE: To investigate the distribution characteristics of polymorphonuclear neutrophil (PMN) in the lungs during the early stage of severe burns and the mechanism of neutrophil elastase (NE) promoting lung injury. METHODS: 6-8-week-old male C57BL/6J mice were selected for the experiments. A 30% total body surface area (TBSA) III degree burn mouse model was established (severe burn group); the Sham-injury group was treated with 37 centigrade water. In the sodium sivelestat intervention group (SV intervention group), NE competitive inhibitor, sivelestat, 100 mg/kg, was injected via tail vein immediately after injury, while other groups received an equal volume of saline. Ten mice were harvested from each group to observe survival for 72 hours. Respiratory function tests were tested at 0 (immediate), 3, 6, 12, and 24 hours after molding. hematoxylin-eosin (HE) and immunohistochemical staining were used to observe lung tissue structure, inflammatory changes and PMN infiltration. The PMN absolute count in mice lung tissue was detected buy flow cytometry. At 6, 12, and 24 hours after molding, PMN counts and the concentration of NE [enzyme linked immunosorbent assay (ELISA)] in peripheral blood plasma, lung tissue, and bronchoalveolar lavage fluid (BALF) were detected. RESULTS: (1) HE staining results showed that compared with the Sham-injury group, the lungs of mice in the severe burn group showed inflammatory changes and PMN infiltration, with more significant changes at 6 hours. Immunohistochemistry results also confirmed that the expression of NE protein released from PMN significantly increased after 6 hours of severe burn injury [(3.79±0.62)% vs. (0.18±0.05)%, t = 11.56, P < 0.01]. (2) Compared with the Sham-injury group, the number of PMN and the concentration of NE in the peripheral blood and lung tissues in the severe burn group were significantly increased (F values were 13.709, 55.350 and 29.890, 13.286, respectively, all P < 0.01), peaking at 6 hours [plasma PMN count (×10⁹/L): 2.92±1.01 vs. 0.92±0.29, lung tissue PMN absolute count (cells): 48 788.03±11 833.91 vs. 1 516.72±415.35, plasma NE (ng/L): 24 522.71±3 842.92 vs. 7 009.34±4 067.86, lung tissue NE (ng/L): 262 189.04±9 695.13 vs. 65 026.03± 16 016.31, all P < 0.01]. The number of PMN in the lung of severely burned mice was highly correlated with NE concentration (r = 0.892, P < 0.001). There was no significantly difference in the PMN absolute count in the BALF of mice between the Sham-injury group and severe burn group (F = 1.403, P > 0.05). The Sham-injury group and severe burn group contained a small amount of NE in the BALF, and the concentration of NE in the BALF of the severely burned 6 hours and 12 hours groups were significantly higher than those of the Sham-injury group (ng/L: 328.58±158.10, 415.30±240.89 vs. 61.95±15.80, both P < 0.05). (3) Kaplan-Meier survival curve showed that the 72-hour survival rate of mice in the SV intervention group was significantly higher than that in the severe burn group (100% vs. 10%, Log-Rank test: χ² = 19.12, P < 0.001). (4) Compared with the Sham-injury group, all lung function indices of the severe burn group decreased significantly. All lung function indices of SV intervention group improved gradually over time, which were significantly better than those of the severe burn group. (5) Compared with the Sham-injury group, the PMN absolute count in lung tissue and the concentration of NE in plasma and lung tissue were significantly higher in the SV intervention group (F values were 46.709, 3.535, 32.701, respectively, all P < 0.05), with a peak at 6 hours. Compared with the severe burn group, the SV intervention group had a higher PMN absolute count in lung tissue (cells: 8 870.80±7 013.89 vs. 25 974.92±22 240.8, P < 0.05), and higher plasma and lung tissue NE concentrations (ng/L: 14 955.94±3 944.41 vs. 21 972.75±4 573.05, 81 956.87±38 658.35 vs. 168 182.30±83 513.91, both P < 0.01) were significantly decreased. CONCLUSIONS In the early stage of severe burns, there is a significant infiltration of PMN into the lungs. The NE promotes lung injury in the early stage of severe burn, and improve lung injury by inhibiting the action of NE.
Animals ; Burns/metabolism* ; Leukocyte Elastase/metabolism* ; Male ; Mice, Inbred C57BL ; Mice ; Neutrophils/metabolism* ; Lung/metabolism* ; Disease Models, Animal ; Neutrophil Infiltration ; Lung Injury/metabolism* ; Glycine/analogs & derivatives* ; Sulfonamides

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

Nine novel compounds, comprising seven tetrahydroanthraquinones (auxarthrolones A-G, 1-7), a γ-butenolide glycoside (malfilamentoside E, 26), and a γ-butenolide (auxarthrolide A, 27), together with eighteen known compounds (8-25) were isolated from rice-based solid culture of Auxarthron umbrinum (A. umbrinum) DSM3193 using the one strain many compounds (OSMAC) approach. The structural elucidation of these compounds was accomplished through nuclear magnetic resonance (NMR), mass spectrometry (MS), and NMR calculation combined with DP4+ analysis or MAEΔΔδ parameter, while the absolute configurations of new compounds were established through single-crystal X-ray diffraction, electronic circular dichroism (ECD) spectroscopic data analysis and/or chemical derivatization. Austrocortilutein (10) and auxarthrol H (14) demonstrated moderate cytotoxicity against U87 and U251 [half maximal inhibitory concentration (IC₅₀) 3.5-12.1 μmol·L^-1]. Additionally, auxarthrolone A (1), auxarthrol H (14), eupolyphagin B (15), and 7-hydroxy-2-(2-hydroxypropyl)-5-methylchromone (17) exhibited torsional effects on fibroblast proliferation challenges induced by oleic acid, thus demonstrating fibroblast proliferation-promoting activity.
4-Butyrolactone/pharmacology* ; Molecular Structure ; Anthraquinones/pharmacology* ; Humans ; Animals ; Mice ; Cell Line, Tumor ; Magnetic Resonance Spectroscopy

The culture of suspended Vero cells is facing difficulties such as low cell viability and long doubling time. To investigate the main reasons for the slow growth and low viability of suspended Vero cells, this study conducted transcriptomic analysis of suspended Vero cells (Vero-XF) and adherent Vero cells (Vero-AD) to screen the differentially expressed genes (DEGs) affecting the growth of suspended cells. In addition, epidermal growth factor (EGF) was supplemented to the culture system to improve the growth of Vero-XF. The results showed that compared with the Vero-AD group, the Vero-XF group had 7 376 significant DEGs. Kyoto encyclopedia of genes and genomes enrichment analysis revealed that the DEGs were mainly enriched in the autophagy and mitophagy pathways. Eleven DEGs were selected and verified by quantitative real-time PCR, which showed up-regulated expression of ATG9B, WIPI2, LAMP2, OPTN, Rab7a, and DEPTOR and down-regulated expression of ATG4D, being consistent with the results of transcriptomic analysis. In addition, the Vero-XF group showed significantly up-regulated expression of ATG101, ATG2A, and STX17 and insignificant change in the expression of NBR1, compared with the Vero-AD group. The protein levels of LC3 and P62 in Vero-XF and Vero-AD were determined by Western blotting, which showed up-regulated expression of LC3Ⅱ/Ⅰ and down-regulated expression of P62 in Vero-XF, indicating a higher level of autophagy. Finally, the exogenous supplementation of EGF at 10, 20, and 30 μg/L in the culture system reduced the autophagy level of Vero-XF by 22.35%, 48.15%, and 71.29%, increased the specific growth rate by 15.48%, 33.33%, and 57.14%, and decreased the apoptosis rate by 2.84%, 15.46%, and 16.23%, respectively. The results of this study preliminarily reveal that the activation of autophagy is one of the reasons for the slow growth of Vero-XF, which provides reference for the subsequent culture of suspended Vero cells.
Animals ; Vero Cells ; Autophagy/genetics* ; Chlorocebus aethiops ; Epidermal Growth Factor/pharmacology* ; Gene Expression Profiling ; Transcriptome ; Cell Survival

Objective:To investigate the protective effects of Mailuoning(MLN)against cisplatin(CP)-induced acute kidney injury(AKI)utilizing network pharmacology and to analyze the underlying mechanism of action related to anti-apoptotic pathways.Methods:Active components of MLN and targets related to AKI were identified using network pharmacology.The active components of MLN were sourced from the TCMSP and ETCM 2.0 databases.The targets of components were predicted using the Swiss Target Prediction tool,and subsequently the targets related to AKI were retrieved from the GeneCards database to identify intersecting targets.A protein-protein interaction network was constructed using the STRING database,and a topological analysis was performed using Cytoscape to identify core targets.Gene Ontology(GO)functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway en-richment analyses were conducted on these core targets.For the animal experiments,forty mice were randomly assigned to four groups:solvent control,MLN toxicity control,CP model,and CP+MLN groups.The MLN group received intraperitoneal injections of MLN at a dose of 15 mL/(kg·d)for ten consecutive days.The CP model and CP+MLN groups were administered a single intraperitoneal injec-tion of CP at 20 mg/kg on day 7.Three days after the CP treatment,plasma levels of blood urea nitrogen(BUN)and creatinine(Cre)were measured.The pathological injury of kidney tissues was as-sessed using hematoxylin-eosin staining.Western blot analysis was utilized to determine the expression of neutrophil gelatinase-associated lipocalin(NGAL)and apoptosis-related proteins in kid-ney tissues.Results:A total of 104 active components of MLN and 224 targets were identified using network pharmacology,and 2 465 targets were identified to be related to AKI,resulting in 117 intersecting targets,of which,17 targets were classified as core targets.KEGG and GO analyses indicated that the apoptosis-related signal transduction pathway might be a crucial pathway through which MLN provided protective effects against AKI.The results of animal experiments confirmed the successful establishment of CP-induced AKI models in mice.Compared with the CP model group,MLN treatment significantly reduced plasma levels of BUN and Cre(P<0.05),inhibited NGAL protein expression in the kidneys(P<0.05),and improved the pathological injury observed in kidney tissues.Furthermore,MLN markedly reduced the expression levels of p-P53(ser 15)and cleaved caspase-3 proteins,as well as the Bax/Bcl-2 ratio in kidney tissues of AKI model mice(P<0.05),while upregulating protein kinase B phosphorylation levels(P<0.05).Conclusion:MLN demonstrates protective effects against CP-induced AKI in mice,potentially through mechanisms related to its anti-apoptotic properties.

In recent years, significant progress has been made in pharmacological research on the treatment of ischemic stroke with monomeric components of traditional Chinese medicine, among which flavonoids have shown good neuroprotective effects. This article reviews the regulatory role of flavonoids in the signaling pathway of ischemic brain injury.

Objective To investigate the clinical efficacy and mechanism of Weiwei Decoction in treating patients with precancerous lesions of gastric cancer(PLGC)differentiated as deficiency-stasis-turbidity syndrome.Methods From August 2021 to August 2023,a clinical observation was performed on 60 patients diagnosed as chronic atrophic gastritis accompanied by mild to moderate dysplasia and differentiated as deficiency-stasis-turbidity syndrome through traditional Chinese medicine(TCM)syndrome differentiation,electronic gastroscopy,and histopathological examination at the Department of Gastroenterology,Guangdong Second Traditional Chinese Medicine Hospital.The patients were randomly divided into a treatment group and a control group using a random number table,with 30 patients in each group.The control group was treated with oral use of Weifuchun Tablets,while the treatment group was given modified Weiwei Decoction according to syndrome differentiation.The treatment course lasted 24 weeks.Before and after treatment,the changes in TCM syndrome scores,gastroscopy and histopathological grading,and expression levels of markers of cancer-associated fibroblasts(CAFs)in gastric mucosal tissues of the two groups were observed.After treatment,the efficacy of TCM syndromes and medication safety were evaluated in both groups.Results(1)After 24 weeks of treatment,the total effective rate in the treatment group was 93.33%(28/30),and that in the control group was 63.33%(19/30).The TCM syndrome efficacy in the treatment group was significantly superior to that in the control group(P＜0.05).(2)After treatment,the TCM syndrome scores in both groups were significantly decreased compared to those before treatment(P＜0.01),and the decrease in the treatment group was significantly superior to that in the control group(P＜0.05).(3)After treatment,the histopathological grading of gastric mucosal atrophy,intestinal metaplasia,and dysplasia in the treatment group was significantly improved compared to that before treatment(P＜0.05),while no significant improvement was presented in the control group(P＞0.05).The improvement in histopathological grading of gastric mucosal atrophy,intestinal metaplasia,and dysplasia in the treatment group was significantly superior to that in the control group(P＜0.05 or P＜0.01).(4)After treatment,the expression levels of CAFs markers of fibroblast activation protein(FAP)and α-smooth muscle actin(α-SMA)in the treatment group were significantly decreased(P＜0.05),while the expression levels of FAP and α-SMA in the control group were significantly increased(P＜0.05)compared to those before treatment.The decrease in FAP and α-SMA expression levels of the treatment group was significantly greater than that of the control group(P＜0.01).(5)During the treatment period,no adverse drug events occurred in either group,indicating high safety.Conclusion Weiwei Decoction has significant therapeutic effect on PLGC patients with deficiency-stasis-turbidity syndrome.Its mechanism may be related to the down-regulation of FAP and α-SMA levels and inhibition of the expression of CAFs.