摘要:ObjectiveThis study aims to systematically evaluate the therapeutic effects of Huaihuasan on ulcerative colitis (UC) in the rats with the syndrome of dampness-heat in the large intestine and explore the potential mechanisms of action.MethodsA rat model of UC due to dampness-heat in the large intestine was successfully established by combining traditional Chinese medicine etiology with trinitrobenzenesulfonic acid (TNBS)/ethanol solution. Rats were randomly allocated into a normal group, a model group, a high-dose (10.58 g·kg-1·d-1) Huaihuasan group, a medium-dose (5.29 g·kg-1·d-1) Huaihuasan group, a low-dose (2.65 g·kg-1·d-1) Huaihuasan group, and a sulfasalazine (0.35 g·kg-1·d-1) group. The body weight changes and the diarrhea and bloody stool scores of the rats in each group were recorded. In addition, pathological changes of the colon tissue were observed to evaluate the therapeutic effects on the intestinal damage and inflammatory infiltration. Immunohistochemistry and real-time fluorescent quantitative PCR were employed to determine the expression levels of zonula occludens-1 (ZO-1) and Occludin in the colon tissue, the serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), the expression of Toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), and nuclear factor-κB p65 subunit (NF-κB p65) in the colorectum, and the mRNA levels of TLR4, MyD88, NF-κB p65, and IL-6 in the intestinal tissue.ResultsCompared with the model group, Huaihuasan effectively slowed down the trend of body weight loss (P<0.01), mitigated diarrhea and bloody stool symptoms, reduce the disease activity index (DAI) (P<0.01), restored the length of the colon (P<0.01), and promoted the recovery of the colon tissue. The immunohistochemistry results showed that compared with the model group, Huaihuasan intervention promoted the expression of ZO-1 and Occludin (P<0.05), reduced the serum levels of IL-6 and TNF-α (P<0.05, P<0.01), and down-regulated the protein levels of TLR4, MyD88, and NF-κB p65 in the colon tissue (P<0.05, P<0.01) and the mRNA levels of TLR4, MyD88, NF-κB p65, and downstream IL-6 (P<0.05).ConclusionHuaihuasan exerts significant therapeutic effects on UC due to dampness-heat in the large intestine by modulating the TLR4/NF-κB signaling pathway, reducing inflammatory mediator levels, and enhancing the intestinal barrier function. These findings provide theoretical support for the clinical application and mechanism study of Huaihuasan in the treatment of UC.
关键词:Huaihuasan;Toll-like receptor 4/ nuclear factor-κB (TLR4/NF-κB) signaling pathway;ulcerative colitis;syndrome of dampness-heat in the large intestine;inflammatory response
摘要:ObjectiveTo investigate the mechanism of Si Junzitang in treating liver injury in rats with spleen Qi deficiency syndrome based on transcriptomics and to experimentally verify its effects.MethodsSixty male SD rats were randomly divided into blank group, model group, low-dose Si Junzitang (6 g·kg-1·d-1), medium-dose Si Junzitang group (12 g·kg-1·d-1), high-dose Si Junzitang group (24 g·kg-1·d-1), and natural recovery group, with 10 rats in each group. A composite multifactorial modeling method (forced swimming + intragastric administration of Xiao Chengqitang + irregular diet) was used to establish a spleen Qi deficiency model. After 30 days of continuous intervention, body weight and 3-hour food intake were measured, and macroscopic symptom scores for spleen Qi deficiency syndrome were evaluated. Serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in each group were detected, and hematoxylin and eosin (HE) staining was used to observe histopathological changes in liver tissue. Transcriptome sequencing (RNA-Seq) was used to identify differentially expressed genes (DEGs) among the blank, model, and high-dose Si Junzitang groups. Gene ontology(GO) and Kyoto encyclopedia of genes and genome(KEGG) enrichment analyses were performed on the DEGs. Immunofluorescence (IF) and Western blot were used to detect NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), Caspase-1, and the N-terminal domain of gasdermin D (GSDMD-N). Immunohistochemistry (IHC) was used to detect the expression of downstream inflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-18 (IL-18).ResultsCompared with the blank group, the model group showed significantly reduced body weight and 3-hour food intake, significantly increased macroscopic symptom scores, and elevated serum AST and ALT levels (P<0.01), with mild inflammatory liver injury observed histologically. Compared with the model group, Si Junzitang at all doses significantly improved these parameters and alleviated liver injury in a dose-dependent manner (P<0.05,P<0.01). RNA-Seq analysis revealed 1 254 DEGs between the blank and model groups, and 842 DEGs between the model and high-dose Si Junzitang groups. GO and KEGG enrichment analyses indicated that the NOD-like receptor signaling pathway was activated in liver injury associated with spleen Qi deficiency, suggesting that the NLRP3 inflammasome may be a key target. Results from IF, IHC, and Westernblot showed that compared with the blank group, the expression of NLRP3, ASC, Caspase-1, GSDMD-N, and the downstream inflammatory cytokines IL-1β, IL-6, and IL-18 were significantly increased in the model group (P<0.01), while these levels were markedly decreased in the high-dose Si Junzitang group (P<0.01).ConclusionSi Junzitang effectively improves mild inflammatory liver injury in rats with spleen Qi deficiency syndrome in a dose-dependent manner. Its mechanism may be associated with inhibition of the NLRP3/ASC/Caspase-1 signaling pathway, downregulation of the pyroptosis executioner protein GSDMD-N, and reduction of pyroptosis-related inflammatory cytokine release.
摘要:ObjectiveTo analyse the efficacy and mechanism of Guizhi Fulingwan in regulating sex hormone disorders in rats with benign prostatic hyperplasia (BPH).MethodsThirty male SD rats were randomly divided into a sham group, a model group, a finasteride group (0.45 mg·kg-1·d-1), and low-dose and high-dose groups of Guizhi Fulingwan (0.135, 0.337 5 g∙kg-1∙d-1), with six in each group. The BPH model was prepared by subcutaneous injection of 3.5 mg∙kg-1∙d-1 testosterone propionate after debridement surgery in all groups except the sham group. The rats in the sham group and the model group were administered with an equal volume of saline by gavage, and the rest of the groups were administered with the corresponding medicinal solution by gavage for 35 days. Histopathology in rats was evaluated by prostate wet weight, volume, index, and hematoxylin-eosin (HE) staining. The serum sex hormone levels of testosterone (T), dihydrotestosterone (DHT), and estradiol (E2) were determined by enzyme-linked immunosorbent assay. The protein expression of the androgen receptor (AR) was detected by immunohistochemistry. The serum metabolism profiles of rats in the sham group, the model group, and the high-dose group of Guizhi Fulingwan were compared by ultra-high performance liquid chromatography tandem Fourier transform mass spectrometry (UHPLCQ Exactive) to screen for metabolic markers and to obtain relevant metabolic pathways.ResultsCompared with those in the sham group, the wet weight, volume, index, serum sex hormone level, and AR protein expression of the prostate in the model group were all elevated (P<0.05, P<0.01), and the histomorphology showed pathological changes. Compared with those in the model group, the wet weight, volume, index, serum sex hormone level, and AR protein expression of the prostate in the intervention groups showed a decreasing trend (P<0.05, P<0.01), and histopathology was improved. Serum metabolomics analysis obtained a total of 40 metabolic markers related to the intervention effect of Guizhi Fulingwan, such as dehydrosafynol, hyoscyamine, and lumichrome, which were involved in the pathways of autophagy, riboflavin metabolism, and retrograde endocannabinoid signaling.ConclusionGuizhi Fulingwan can effectively regulate sex hormone disorders in BPH rats, and its mechanism may be related to autophagy, riboflavin metabolism, and retrograde endocannabinoid signaling.
摘要:ObjectiveTo investigate whether Danggui Shaoyaosan (DSS) inhibits oxidative stress and alleviates inflammation via the Ras homolog family member A (RhoA)/Rho-associated coiled-coil containing protein kinase 1 (ROCK)/nuclear factor kappa-B (NF-κB) signaling pathway, thereby delaying the progression of diabetic kidney disease (DKD) and exerting a nephroprotective effect.MethodsEight db/m mice were assigned to the normal group, and forty 8-week-old db/db mice were randomly divided into the model group, DSS low-dose group (8.39 g·kg-1), DSS medium-dose group (16.77 g·kg-1), DSS high-dose group (33.54 g·kg-1), and irbesartan group (0.025 g·kg-1), with eight mice in each group. All groups were administered the corresponding treatment by gavage once daily for 12 weeks. The normal and model groups received an equal volume of saline. During administration, changes in body weight, fasting blood glucose (FBG), and 24 hour urinary protein (24 h UTP) were observed. After 12 consecutive weeks of administration, hematoxylin-eosin (HE) staining and Masson's trichrome staining were used to observe renal histopathological changes in each group. The levels of reactive oxygen species (ROS) in renal tissue were detected using the dihydroethidium (DHE) method. The expression levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in renal tissue were determined. Serum interleukin-1β (IL-1β) and interleukin-6 (IL-6) levels were measured using enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of RhoA, ROCK1, and NF-κB p65 in renal tissues were detected by Real-time quantitative polymerase chain reaction (Real-time PCR). Protein expression levels of fibronectin (FN), Collagen Ⅳ(Col Ⅳ), transforming growth factor-β1 (TGF-β1), RhoA, ROCK, and NF-κB p65 in renal tissues were determined by Western blot.ResultsCompared with the normal group, the model group showed significantly increased body weight, FBG, and 24 h UTP levels (P<0.01), elevated serum IL-1β and IL-6 levels, enlarged glomerular volume, diffuse mesangial expansion, increased mesangial matrix, and marked collagen fiber proliferation in renal tissues. SOD activity was decreased, while MDA, ROS, RhoA, ROCK1, and NF-κB p65 mRNA expression levels were increased (P<0.01), and the protein expression levels of FN, Col Ⅳ, TGF-β1, RhoA, ROCK, and NF-κB p65 were also elevated (P<0.01). Compared with the model group, the DSS low-, medium-, and high-dose groups and the irbesartan group showed reductions in body weight, FBG, and 24 h UTP, decreased serum IL-1β and IL-6 levels, varying degrees of improvement in renal histopathology, increased SOD activity, decreased MDA levels, reduced ROS expression, and significantly downregulated RhoA, ROCK1, and NF-κB p65 mRNA expression (P<0.05, P<0.01), as well as reduced protein expression levels of FN, Col Ⅳ, TGF-β1, RhoA, ROCK, and NF-κB p65 (P<0.05, P<0.01).ConclusionDSS can alleviate oxidative stress and inflammation, reduce extracellular matrix deposition, and delay renal fibrosis progression in db/db mice. Its mechanism may be related to the inhibition of the RhoA/ROCK/NF-κB signaling pathway, thereby exerting a therapeutic effect on DKD.
关键词:diabetic kidney disease;Danggui Shaoyaosan;Ras homolog family member A (RhoA)/Rho-associated coiled-coil containing protein kinase 1 (ROCK)/nuclear factor kappa-B (NF-κB) signaling pathway;oxidative stress;inflammation
摘要:ObjectiveTo investigate the effect of Niuhuang Qingxinwan (NHQXW) in improving intracerebral hemorrhage (ICH) with Tanre Fushi (phlegm-heat and fu-organ excess) syndrome by maintaining blood-brain barrier (BBB) integrity, and to explore its potential mechanism.MethodsMale mice were administered with 15% autologous feces for 3 consecutive days to simulate spontaneous Tanre Fushi syndrome, followed by surgical induction of collagenase-induced ICH on the fourth day. Mice were randomly assigned to seven groups: Sham, Sham+NHQXW-H, collagenase, collagenase+feces, and NHQXW intervention groups at low (NHQXW-L, 0.225 g·kg-1), medium (NHQXW-M, 0.45 g·kg-1), and high (NHQXW-H, 0.9 g·kg-1) doses. Treatments were administered for 3 days after surgery. NHQXW effects on Tanre Fushi syndrome were assessed via fecal water content and small intestinal carbon propulsion rate. Protective effects of NHQXW against ICH with Tanre Fushi syndrome were evaluated by measuring hematoma volume, neurological deficits, and brain water content. BBB integrity was further assessed using Evans blue staining, hematoxylin-eosin (HE) staining, immunofluorescence, and Western blot for Claudin-5, plasmalemma vesicle-associated protein (PLVAP), matrix metalloproteinase (MMP)-2, and MMP-9. The potential mechanism of NHQXW was investigated by detecting protein expression of protein kinase B (Akt), extracellular signal-regulated kinase 1/2 (ERK1/2), signal transducer and activator of transcription 3 (STAT3), Yes-associated protein (YAP), and their phosphorylated forms.ResultsCompared with the collagenase+feces group, NHQXW-M and NHQXW-H significantly reduced fecal water content (P<0.05, P<0.01) and intestinal propulsion rate (P<0.01), alleviated neurological deficits (P<0.01), decreased hematoma volume (P<0.01) and Evans blue extravasation (P<0.01), increased Claudin-5 protein expression (P<0.05, P<0.01) and fluorescence intensity (P<0.01), and decreased PLVAP protein expression (P<0.01) and fluorescence intensity (P<0.05, P<0.01), as well as MMP-2 (P<0.05, P<0.01) and MMP-9 (P<0.01) expression. NHQXW-H downregulated p-Akt (P<0.05), p-ERK1/2 (P<0.05), p-STAT3 (P<0.01), and p-YAP (P<0.05), with the most significant effect observed on STAT3 phosphorylation.ConclusionNHQXW effectively alleviates neurological deficits and BBB injury in ICH mice with Tanre Fushi syndrome, primarily by inhibiting STAT3 activation.
关键词:Niuhuang Qingxinwan;Tanre Fushi syndrome;intracerebral hemorrhage;blood-brain barrier;signal transducer and activator of transcription 3 (STAT3)
摘要:ObjectiveThis study aims to analyze the pharmacodynamic material basis and multi-target mechanism of action of Banxia Baizhu Tianmatang combined with Danggui Shaoyaosan in the treatment of Meniere's disease(MD).MethodsUltra-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) (mobile phase: gradient elution with 0.1% formic acid aqueous solution-acetonitrile. Mass spectrometry scanning range: m/z 90-1 300) was used to identify the chemical components of the compound recipe and components absorbed into blood. The core mechanism was predicted by combining network pharmacology (target screening via SwissTargetPrediction and GeneCards databases, and construction of protein-protein interaction (PPI) network by STRING) and molecular docking (evaluated by Autodock, with binding energy ≤ -5.0 kcal·mol-1). For animal experiment validation, 36 Sprague Dawley (SD) rats were divided into a blank group, a model group (postauricular injection of lipopolysaccharide (LPS) at 1 mg·kg-1), low/medium/high-dose Chinese medicine groups (5.94, 11.88, and 23.76 g·kg-1·d-1, respectively), and Western medicine group (betahistine at 0.1 mg·kg-1·d-1). After eight weeks of intervention, the gene and protein expressions in cochlear tissue were detected.Results①A total of 2 831 chemical components and 173 components absorbed into blood were identified, with terpenoids showing the highest absorption rate into blood(10.28%). ②60 common drug-disease targets were screened, with core targets including tumor necrosis factor-α(TNF-α),interleukin-6(IL-6), Toll-like receptor 4(TLR4), angiotensin-converting enzyme(ACE), and endothelial nitric oxide synthase 3(NOS3).These targets were enriched in the nuclear factor-κB(NF-κB) signaling pathway and renin-angiotensin system(P<0.05). Molecular docking showed that the active component YC-1 had a strong binding ability to TNF(binding energy-9.66 kcal·mol-1). ③In animal experiments, the high-dose Chinese medicine group significantly down-regulated the expression of pro-inflammatory factors TNF mRNA(P<0.01)and up-regulated vascular regulatory factors NOS3 protein(P<0.01), and alleviated cochlear pathological damage[hematoxylin eosin (HE) score: from 4 to 2].ConclusionThis compound recipe synergistically regulates the TNF/NF-κB inflammatory pathway and ACE/NOS3 vascular homeostasis pathway through flavonoids, triterpenoids, and other components, thereby inhibiting endolymphatic hydrops and cochlear damage. It provides a scientific basis for the theory of "simultaneous treatment of phlegm and blood stasis" in traditional Chinese medicine.
摘要:ObjectiveTo investigate the possible mechanism of Shufeng Jiedu capsules (SFJD) in alleviating influenza A (H1N1) virus pneumonia and focus on its effect on Toll-like receptor (TLR) signaling pathway in respiratory epithelial cells.MethodsA mouse model of viral pneumonia was established via the A/PR/8/34 (PR8) strain of influenza A virus. Mice were randomly divided into a normal group, a PR8 infection (PR8) group, and an SFJD group (8.4 g·kg-1), with 10 mice in each group. The day of infection was designated as day 1. The SFJD group was administered intragastrically at a volume of 20 mL·kg-1 daily, while the normal and PR8 groups were given an equal volume of deionized water. Micro-computed tomography (Micro-CT) was performed on day 5, and the mice were dissected to collect their lungs, after which the lung index was calculated to verify the therapeutic effect of SFJD. Single-cell sequencing was used to analyze the differentially expressed genes in respiratory epithelial cells. Multiplex fluorescence immunohistochemistry was employed to detect the expression of TLR, tumor necrosis factor receptor-associated factor 6 (TRAF6), and myeloid differentiation factor 88 (MyD88) proteins in epithelial cell adhesion molecule (EpCAM)-positive cells, and the proportion of respiratory epithelial cells expressing TLR pathway proteins was calculated. Respiratory epithelial cells were then sorted by flow cytometry, and Western blot was used to detect the expression of TLR, MyD88, TRAF6, Toll-interleukin receptor domain-containing adaptor inducing interferon-β (TRIF), inhibitor of κB kinase α (IKKα), and nuclear factor-κB (NF-κB) in the sorted epithelial cells. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in lung tissue.ResultsAt the transcriptional level, SFJD reversed the expression of TLR signaling pathway genes in respiratory epithelial cells, downregulating multiple TLR signaling pathway-related genes (P<0.01). At the protein level, SFJD significantly reduced the proportion of respiratory epithelial cells expressing TLR3 (P<0.05), the expression levels of TLR2, TLR3, TLR4, TRIF, TRAF6, IKKα, and NF-κB in epithelial cells(P<0.05, P<0.01), as well as the levels of pro-inflammatory cytokines IL-1β and TNF-α in lung tissue (P<0.01).ConclusionSFJD may alleviate viral pneumonia by suppressing the expression of TLR in respiratory epithelial cells and their subsequent signaling cascades.
摘要:ObjectiveTo evaluate the pharmacological effects of verbenalin on both in vitro and in vivo infection models of human coronavirus 229E (HCoV-229E) and to preliminarily explore the antiviral mechanism of verbenalin through proteomic analysis.MethodsIn vitro, the cell counting kit-8 (CCK-8) for cell proliferation and viability assessment was used to establish a model of HCoV-229E-induced injury in human lung adenocarcinoma cells(A549). A549 cells were divided into five groups: normal group, model group, and three verbenalin treatment groups (125, 62.5, and 31.25 μmol·L-1). The cell protective activity of verbenalin was evaluated through cell viability assay and immunofluorescence staining. In vivo, 30 BALB/c mice were randomly divided into normal group, model group, chloroquine group, and high-dose, low-dose verbenalin groups (40 and 20 mg·kg-1), with six mice per group. An HCoV-229E-induced mouse lung injury model was established to evaluate the therapeutic effects of verbenalin. Lung injury was assessed by detecting the lung index and lung inhibition rate. The severity of pulmonary inflammation cytokines was measured by enzyme-linked immunosorbent assay (ELISA), while the lung morphology and structure were analyzed by micro-computed tomography (Micro-CT). Hematoxylin and eosin (HE) staining was used to assess histopathological changes in lung tissue. Additionally, four-dimensional data-independent acquisition (4D-DIA) proteomics was employed to preliminarily explore the potential mechanisms of verbenalin in treating HCoV-229E-induced lung injury in mice, through differential protein expression screening, functional annotation, enrichment analysis, and protein-protein interaction network analysis.ResultsThe A549 cells were infected with HCoV-229E at the original viral titer for 36 hours to establish an in vitro infection model. The maximum non-toxic concentration of verbenalin was 125 μmol·L-1, and the half-maximal cytotoxic concentration (CC50) was 288.8 μmol·L-1. Compared with the normal group, the model group showed a significant decrease in cell viability (P<0.01), a significant increase in the proportion of dead cells (P<0.01), mitochondrial damage, and a significant reduction in mitochondrial membrane potential (P<0.01). After treatment with different concentrations of verbenalin (125, 62.5, and 31.25 μmol·L-1), cell viability was significantly increased (P<0.01), and the proportion of dead cells was reduced (P<0.01), with mitochondrial membrane potential restored (P<0.01). In vivo experiments further confirmed the therapeutic effect of verbenalin on HCoV-229E-infected mice. Compared to the normal group, the model group showed a significant increase in the lung index (P<0.01), severe lung tissue injury, lung volume enlargement, and a significant increase in the expression of inflammatory cytokines, including interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) (P<0.01). In contrast, in the verbenalin treatment groups, these pathological changes were significantly improved, with a reduction in the lung index (P<0.01), alleviation of lung tissue injury, reduced lung volume enlargement, and a significant decrease in inflammatory cytokine expression (P<0.01). Proteomics analysis revealed that, compared to the normal group, the model group showed enrichment in several antiviral immune-related signaling pathways, including the nuclear factor-κB (NF-κB) signaling pathway (P<0.05). Compared to the model group, the verbenalin treatment group showed enrichment in several signaling pathways related to inflammatory response and autophagy (P<0.05), suggesting that verbenalin may exert its antiviral and anti-inflammatory effects by regulating these pathways.ConclusionVerbenalin demonstrates significant therapeutic effects in both in vitro and in vivo HCoV-229E infection models, with its mechanism likely related to the NOD-like receptor protein 3 (NLRP3) inflammasome pathway and mitochondrial autophagy.
摘要:ObjectiveTo study the anti-inflammatory and immunomodulatory effects of Shufeng Jiedu capsules in a mouse model infected with human coronavirus 229E (HCoV-229E).MethodsForty-eight BALB/c mice were randomly divided into a normal group, a model group, a chloroquine positive group (0.075 8 g·kg-1), and high-dose, medium-dose, and low-dose groups of Shufeng Jiedu capsules (1.872、0.936、0.468 g·kg-1), with eight mice in each group. The coronavirus infection model was established by intranasal infection with the HCoV-229E virus solution. On the fourth day after infection, the mice were killed by cervical dislocation. The pathological changes in the lung were evaluated by weighing the wet weight of the lung and calculating the lung index. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot (WB) techniques were used to detect the expression levels of key genes and proteins such as Toll-like receptor 4 (TLR4), Toll/interleukin-1 receptor (TIR)-domain-containing adapter inducing interferon-β (TRIF), tumor necrosis factor receptor-associated factor 6 (TRAF6), TANK-binding kinase 1 (TBK1), phospho-TANK-binding kinase 1 (p-TBK1), interferon regulatory factor 3 (IRF3), and phospho-interferon regulatory factor 3 (p-IRF3) in lung tissue.ResultsCompared with that in the normal group, the lung index of the mice in the model group was significantly increased (P<0.01). There was a large amount of inflammatory exudation in the pulmonary interstitium, and the expression of TLR4, TRIF, TRAF6, TBK1, p-TBK1, IRF3, and p-IRF3 proteins was significantly increased (P<0.01), indicating that HCoV-229E caused severe pulmonary inflammation. Compared with the model group, Shufeng Jiedu capsules at each dose significantly reduced the lung index of mice (P<0.01), among which the lung index inhibition rate of the high-dose and medium-dose groups was 78.18% and 79.27%. At the same time, Real-time PCR and WB results showed that the medium-dose Shufeng Jiedu capsules significantly reduced the gene and protein expression levels of TLR4, TRIF, TRAF6, TBK1, p-TBK1, and p-IRF3 (P<0.05).ConclusionShufeng Jiedu capsules can alleviate lung inflammation and tissue injury caused by coronavirus infection by inhibiting the excessive activation of the TLR4/TRIF/TBK1 signaling pathway.
摘要:ObjectiveEndothelial cell dysfunction being the core link. This study explores the molecular mechanism of Danshen Tongluo formula in treating coronary artery disease-dominated panvascular disease with endothelial cell changes as the core through animal experiments and single-cell transcriptome sequencing.MethodsA rat model of coronary artery disease-dominated panvascular disease was established by ligating the left anterior coronary artery. Rats were randomized into a blank group, a model group, and a Danshen Tongluo formula (28 mg·kg-1·d-1) group. The efficacy was evaluated by examining the cardiac ultrasound, determination of the plasma level of N-terminal pro-brain natriuretic peptide, and pathological staining. After single-cell sequencing, SingleR package, public datasets, and related literature were used for annotation of the cells. Cell chat was used for intercellular communication and ligand-receptor analysis, and scmetabolism was used for metabolic analysis of endothelial cells.ResultsAnimal experiments showed that Danshen Tongluo formula reduced the N-terminal pro-brain natriuretic peptide ( NT-proBNP ) level (P<0.05), ameliorated myocardial cell damage and fibrosis, and increase left ventricular ejection fractions (LVEF) in the rat model of heart failure after myocardial infarction(P<0.05). Single-cell sequencing results showed that Danshen Tongluo formula increased the proportion of arterial endothelial cells, venous endothelial cells, and capillary-arterial endothelial cells, while reducing the proportion of capillary-venous endothelial cells. In addition, this formula increased the interaction intensity of endothelial cells with cardiomyocytes and M1 macrophages and reduced the interaction intensity of endothelial cells with fibroblasts and T cells. Danshen Tongluo formula upregulated CXCL12-CXCR4 signaling in endothelium-B cells and Ptprm-Ptprm signaling in endothelial endothelial cells, while downregulating Mif-(CD74+CXCR44) signaling in endothelium-M1 macrophages and Mif-(CD74+CD44) signaling in endothelium-M2 macrophages. It reduced the citric acid cycle, oxidative phosphorylation, and glycolysis and increased the glycolysis/oxidative phosphorylation ratio in endothelial cells. GO and KEGG enrichment analysis showed that arterial endothelial cells, venous endothelial cells, and venous capillary endothelial cells can all regulate oxidative phosphorylation, cell adhesion molecules, and tyrosine metabolism. Lymphatic endothelial cells regulate immunity and vascular constriction to participate in the metabolism of various amino acids and fatty acids.ConclusionDanshen Tongluo Formula can ameliorate coronary artery disease-dominated panvascular disease by changing the composition of endothelial cells and regulating the communication between myocardial endothelial cells and non-endothelial cells.
摘要:ObjectiveThrough multimodal research methods including medication rule mining, network pharmacology, molecular docking and dynamics simulation, and in vivo animal experiments, this study aims to speculate and verify the core composition (Ginseng Radix et Rhizoma Rubra-Salviae Miltiorrhizae Radix et Rhizoma-Notoginseng Radix et Rhizoma) and efficacy (Qi-invigorating and blood-activating) of the drug combination in Yitangkang Compound for improving diabetic cardiomyopathy (DCM), investigate the interaction relationship and binding strength between core active ingredients of the drug combination and key signaling pathway targets, and further explore the mechanism by which the Qi-invigorating and blood-activating drug combination regulates the calcium signaling pathway to improve cardiac function in DCM rats.MethodsThe Ancient and Modern Medical Cases Cloud Platform was used to construct a DCM prescription database, and the "Analysis Method" module of the platform was applied to mine and summarize medication rules, thereby determining the core composition of the Qi-invigorating and blood-activating drug combination in Yitangkang. Drug-active ingredient-signaling pathway-core target-disease analysis and visualization were conducted by combining network pharmacology with the Traditional Chinese Medicine System Pharmacology Platform (TCMSP) database, SwissTargetPrediction platform, GeneCards database, MetaScape database, CytoScape software, etc. Then, molecular docking was performed via the CB-Dock2 platform, and molecular dynamics simulation of the high-binding-strength docking complexes was carried out by Gromacs software. Finally, in vivo animal experiments were carried out. Twenty-eight Sprague Dawley (SD) rats meeting the research criteria were divided into a normal group, a model group, a drug combination group (3.3 g·kg-1), and a Yitangkang group (20 g·kg-1). A type 2 diabetes mellitus (T2DM) rat model was established by high-fat diet feeding combined with intraperitoneal injection of streptozotocin (STZ), followed by continuous feeding for eight weeks until the DCM model was successfully established. During this period, the traditional Chinese medicine (TCM) compound and drug combination were administered for prevention and treatment intervention. Meanwhile, changes in blood glucose, body weight, and heart index of each group were monitored. Cardiac function was assessed by echocardiography, and electrophysiological signals were detected by an electrocardiogram. The heart tissue was observed for pathological changes by hematoxylin-eosin (HE) and Masson staining, and the expression of L-type calcium channel (CACNA1C), calmodulin (CALM1), calcium/calmodulin-dependent protein kinase Ⅱδ (CAMK2D), and neuronal nitric oxide synthase (NOS1) proteins in the calcium signaling pathway of myocardial tissue was detected by Western blot.ResultsIn 62 DCM prescriptions, Ginseng Radix et Rhizoma Rubra, Salviae Miltiorrhizae Radix et Rhizoma, and Notoginseng Radix et Rhizoma were used most frequently. Their meridian tropism mainly involved the spleen, heart, and lung, and their sweet and warm properties were prominent. The drugs for tonifying or blood-activating and stasis-resolving ranked top. In association rule analysis, (Ginseng Radix et Rhizoma Rubra, Salviae Miltiorrhizae Radix et Rhizoma)-Notoginseng Radix et Rhizoma had the highest lift. Network pharmacology obtained 75 active ingredients of the drug combination, 714 drug combination action targets, 2 702 disease targets, and 286 intersection targets. Protein-protein interaction (PPI) network predicted nine interaction component-targets (nine active ingredients and four calcium signaling pathway target genes). Molecular docking showed the four complexes with the lowest binding energy were 2f3z-ginsenoside Re, 1cll-quercetin, 9blh-(6S)-6-(hydroxymethyl)-1,6-dimethyl-8,9-dihydro-7H-naphtho[8,7-g]benzofuran-10,11-dione, and 5vv0-miltionone Ⅱ. Dynamics simulation showed the CALM1-quercetin complex had the strongest binding affinity. The animal experiment results revealed that compared with the normal group, the model group showed significant changes in blood glucose, body weight, myocardial tissue morphology, heart index, cardiac function, electrophysiological indexes, and the expression levels of CACNA1C, CALM1, CAMK2D, and NOS1 proteins (P<0.05, P<0.01). Compared with the model group, the Yitangkang group had a certain improvement effect on the above indexes (P<0.05, P<0.01). Compared with the Yitangkang group, the drug combination group showed no significant difference in improving myocardial tissue morphology, heart index, cardiac function, electrophysiological indexes, and the expression of CACNA1C, CALM1, CAMK2D, and NOS1 proteins, except for blood glucose and body weight.ConclusionGinseng Radix et Rhizoma Rubra, Salviae Miltiorrhizae Radix et Rhizoma, and Notoginseng Radix et Rhizoma are the core Qi-invigorating and blood-activating drug combination in Yitangkang Compound. They have a good preventive and therapeutic effect on STZ-induced DCM in rats, and their mechanism of action may be related to the regulation of the calcium signaling pathway.
关键词:diabetic cardiomyopathy;Yitangkang Compound;Ginseng Radix et Rhizoma Rubra-Salviae Miltiorrhizae Radix et Rhizoma-Notoginseng Radix et Rhizoma;medication rule mining;network pharmacology;molecular docking and dynamics simulation;calcium signaling pathway
SONG Changyue, LI Siyu, HUANG Fengyu, QI Mingzhu, DING Daiyue, DENG Shuangfei, LI Heqiao, XIE Jinghong, WANG Guohua, ZANG Chen, XU Hong, SU Xiaohui, KONG Xiangying
摘要:ObjectiveTo investigate the protective effects and mechanisms of Bushen Zhuyun prescription (BSZY) on abortion rats with kidney deficiency-corpus luteum inhibition syndrome.MethodsAn abortion rat model with kidney deficiency-corpus luteum inhibition syndrome was constructed. Pregnant mice aged 8-10 weeks were randomly divided into a control group (Control), a model group (Model), low-dose BSZY (BSZY-L), medium-dose BSZY (BSZY-M), and high-dose BSZY (BSZY-H) groups (2.57, 5.14, 10.28 g·kg-¹), and a Zishen Yutai Pill (ZSYT) group (1.575 g·kg-¹). Hematoxylin-eosin (HE) staining was used to evaluate histopathological changes in ovarian and decidual tissue of rats in each group. Enzyme-linked immunosorbent assay (ELISA) was employed to measure levels of estrogen (E₂), progesterone (P), luteinizing hormone (LH), prolactin (PRL), and follicle-stimulating hormone (FSH) in serum. The candidate targets of BSZY were obtained from the Traditional Chinese Medicine System Pharmacology Platform (TCMSP) and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine (TCMIP) v2.0 databases, while disease targets for recurrent spontaneous abortion (RSA) were retrieved from GeneCards, DrugBank, Online Mendelian Inheritance in Man (OMIM), and Therapeutic Target Database (TTD). The intersection targets were identified by the Venny 2.1.0 platform. Pathway enrichment analysis was conducted based on the Metascape database to predict the potential mechanisms of BSZY. Additionally. Western blot was used to verify the effects of BSZY on the expression of estrogen receptor (ERα), phosphatidylinositol 3-kinase (PI3K), and protein kinase B (Akt) and explore its protective mechanism on RSA rats.ResultsCompared with the control group, the model group exhibited significantly decreased uterine, ovarian, and embryonic wet weights (P<0.05, P<0.01), with an abortion rate of 57.18%. The ovarian tissue showed varying degrees of reduction in primordial follicles, primary follicles, mature follicles, and corpora lutea, along with a large number of atretic follicles. The endometrium was thinner, and decidual tissue exhibited cellular edema and disorganized arrangement. In contrast, compared with the model group, the BSZY groups at all doses and the ZSYT group demonstrated increased uterine, ovarian, and embryonic wet weights, along with a reduced abortion rate. The number of primordial follicles, primary follicles, mature follicles, and corpora lutea increased, while atretic follicles decreased. The endometrium thickened, and decidual tissue displayed normal cellular structure with tight arrangement. Additionally, the model group showed significantly decreased levels of E₂, P, PRL, and FSH in serum (P<0.05, P<0.01), along with a decreasing trend in LH level. In contrast, the BSZY groups at all doses exhibited significantly elevated levels of E₂, P, LH, PRL, and FSH in serum (P<0.05, P<0.01). Network pharmacology predictions suggested that BSZY may exert protective effects against abortion in rats by activating the ERα/PI3K/Akt signaling pathway. Western blot results confirmed that BSZY significantly upregulated the expression of ERα, PI3K, and p-Akt proteins (P<0.05, P<0.01).ConclusionBSZY has a protective effect on the abortion rats with kidney deficiency-corpus luteum inhibition syndrome, possibly by activating the ERα/PI3K/Akt signaling pathway to reduce ovarian apoptosis and regulate endocrine function, thereby lowering the abortion rate.
关键词:Bushen Zhuyun prescription;recurrent spontaneous abortion;model combining disease with syndrome;estrogen receptor alpha (ERα)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway
摘要:ObjectiveTo investigate the mechanism of Forsythiae Fructus-Lonicerae Japonicae Flos(FF) in the treatment of acute lung injury(ALI) by investigating the effects of FF on serum metabolomics of rats with ALI.MethodsThirty male SD rats were acclimated for 1 week, and 6 rats were randomly selected as the blank group. The other 24 rats were injected with lipopolysaccharide(LPS) solution by tracheal drip to establish an ALI model. After successful model establishment, the rats were randomly divided into the model group, the FF low-dose group(3.0 g·kg-1), the FF high-dose group(6.0 g·kg-1), and the dexamethasone group(5 mg·kg-1), with six rats in each group. The FF low- and high-dose groups and the dexamethasone group were received daily oral administration of the corresponding drug solution, and the blank group and the model group were gavaged with an equal amount of saline, treatment was administered continuously for 3 d. The pathological conditions of rat lung tissues were evaluated by hematoxylin-eosin(HE) staining, wet/dry mass ratio(W/D) of the lung tissues, and protein concentration in rat bronchoalveolar lavage fluid(BALF). Metabolomic analysis of rat serum was performed by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS), combined with multivariate statistical analysis, the potential biomarkers of FF in treating ALI were screened by variable importance in the projection(VIP) value>1, P<0.05 from t-test, and log2fold change(FC)>1 or log2FC<-1. Kyoto Encyclopedia of Genes and Genomes(KEGG) database combined with MetaboAnalyst were used for pathway analysis of the screened differential metabolites. The protein expression levels of sphingosine-1-phosphate(S1P), phosphatidylinositol 3-kinase(PI3K), protein kinase B1(Akt1), and phosphorylated Akt1(p-Akt1) were examined by Western bolt. The expression levels of interleukin(IL)-6, IL-1β, and tumor necrosis factor(TNF)-α in BALF were detected by enzyme-linked immunosorbent assay(ELISA).ResultsCompared with the blank group, rats in the model group showed ALI pathological features such as alveolar lumen dilatation, interstitial hemorrhage and massive inflammatory cell infiltration, and the protein concentration in BALF and W/D of the lung tissues were significantly elevated(P<0.01). Compared with the model group, the low- and high-dose groups of FF as well as the dexamethasone group exhibited reduced pulmonary bronchial hemorrhage in rats, and the protein concentration in BALF and W/D were significantly decreased(P<0.05), and the lung injury was significantly alleviated. Analysis of rat serum metabolomics revealed that FF downregulated 38 biomarkers. Pathway enrichment analysis showed that FF primarily exerted therapeutic effects through 7 key metabolic pathways, including arginine biosynthesis, sphingomyelin metabolism, alanine, aspartate and glutamate metabolism, taurine and hypotaurine metabolism, α-linolenic acid metabolism, niacin and nicotinamide metabolism, and retinol metabolism. The results of Western bolt and ELISA showed that, compared with the blank group, the model group exhibited significantly elevated expression levels of S1P, PI3K, Akt1 and p-Akt1 proteins in the lung tissues, as well as increased expression levels of IL-6, IL-1β and TNF-α in BALF(P<0.01). Compared with the model group, the expression levels of the aforementioned indicators were significantly downregulated in the low- and high-dose FF groups as well as the dexamethasone group(P<0.05, P<0.01).ConclusionFF may play a role in ALI by regulating amino acid metabolism and lipid metabolism, and its mechanism may be related to the inhibition of S1P/PI3K/Akt1 signaling pathway to attenuate the inflammatory response caused by ALI.
摘要:ObjectiveTo investigate the ameliorative effects of quercetin on neuropsychiatric symptoms associated with vascular dementia (VaD) and to elucidate the molecular mechanism, specifically whether quercetin inhibits pro-inflammatory activation of microglia by modulation of the receptor-interacting serine/threonine-protein kinase 1 (RIPK1)/NOD-like receptor protein 3 (NLRP3)/Caspase-1 signaling pathway, thereby promoting myelin repair in the medial prefrontal cortex (mPFC).MethodsA C57BL/6J mouse model of VaD with neuropsychiatric symptoms was established by bilateral common carotid artery stenosis (BCAS) combined with chronic restraint stress (CRS). Mice were randomly divided into a sham group, a model group, low-dose, medium-dose, and high-dose quercetin groups (30, 60, 120 mg·kg-1·d-1), and a fluoxetine group (10 mg·kg-1·d-1). After intervention, depressive- and anxiety-like behaviors were assessed by the sucrose preference test (SPT), forced swim test (FST), open field test (OFT), and elevated plus maze (EPM). mPFC tissue was collected. Immunofluorescence (IF) was used to detect myelin basic protein (MBP) expression and microglial morphology. Western blot was used to measure the protein level of MBP, myelin oligodendrocyte glycoprotein (MOG), myelin-associated glycoprotein (MAG), inducible nitric oxide synthase (iNOS), CD86, RIPK1, phosphorylated RIPK1 (Ser166), NLRP3, and Caspase-1. Enzyme-linked immunosorbent assay (ELISA) was used to determine the level of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β).ResultsCompared with the sham group, the model group exhibited significant depressive- and anxiety-like behaviors (P<0.01), significantly decreased protein expression of MBP, MOG, and MAG in the mPFC (P<0.01), activated microglia (characterized by enlarged cell bodies, reduced protrusions, and upregulated iNOS and CD86 expressions, P<0.01), and significantly elevated p-RIPK1/RIPK1 ratio, NLRP3, Caspase-1 protein expression, and level of TNF-α, IL-6, and IL-1β (P<0.01, P<0.05). Compared with the model group, the quercetin treatment (especially at medium and high doses) significantly ameliorated these behavioral abnormalities (P<0.05, P<0.01), increased the expression of MBP (protein and fluorescence intensity), MOG, and MAG in the mPFC (P<0.05, P<0.01), suppressed excessive microglial activation (characterized decreased cell bodies, increased protrusions, and downregulated iNOS and CD86 expressions, P<0.01), and significantly reduced the p-RIPK1/RIPK1 ratio, NLRP3, Caspase-1 protein expression, and inflammatory cytokine levels (P<0.01).ConclusionQuercetin effectively alleviates neuropsychiatric symptoms in VaD mice. Its mechanism may be associated with the inhibition of microglial inflammatory activation mediated by the RIPK1/NLRP3/Caspase-1 signaling pathway, thereby promoting myelin repair in the mPFC region.
摘要:ObjectiveThis study aims to develop and validate a novel multimodal predictive model, termed criss-cross network(CCNet)-directed graph neural network(DGNN)(CGN), for accurate assessment of pulmonary nodule progression in high-risk individuals for lung cancer, by integrating longitudinal chest computed tomography(CT) imaging with both traditional Chinese and western clinical evaluation data.MethodsA cohort of 4 432 patients with pulmonary nodules was retrospectively analyzed. A twin CCNet was employed to extract spatiotemporal representations from paired sequential CT scans. Structured clinical assessment and imaging-derived features were encoded via a multilayer perceptron, and a similarity-based alignment strategy was adopted to harmonize multimodal imaging features across temporal dimensions. Subsequently, a DGNN was constructed to integrate heterogeneous features, where nodes represented modality-specific embeddings and edges denoted inter-modal information flow. Finally, model optimization was performed using a joint loss function combining cross-entropy and cosine similarity loss, facilitating robust classification of nodule progression status.ResultsThe proposed CGN model demonstrated superior predictive performance on the held-out test set, achieving an area under the receiver operating characteristic curve(AUC) of 0.830, accuracy of 0.843, sensitivity of 0.657, specificity of 0.712, Cohen's Kappa of 0.417, and F1 score of 0.544. Compared with unimodal baselines, the CGN model yielded a 36%-48% relative improvement in AUC. Ablation studies revealed a 2%-22% increase in AUC when compared to simplified architectures lacking key components, substantiating the efficacy of the proposed multimodal fusion strategy and modular design. Incorporation of traditional Chinese medicine (TCM)-specific symptomatology led to an additional 5% improvement in AUC, underscoring the complementary value of integrating TCM and western clinical data. Through gradient-weighted activation mapping visualization analysis, it was found that the model's attention predominantly focused on nodule regions and effectively captured dynamic associations between clinical data and imaging-derived features.ConclusionThe CGN model, by synergistically combining cross-attention encoding with directed graph-based feature integration, enables effective alignment and fusion of heterogeneous multimodal data. The incorporation of both TCM and western clinical information facilitates complementary feature enrichment, thereby enhancing predictive accuracy for pulmonary nodule progression. This approach holds significant potential for supporting intelligent risk stratification and personalized surveillance strategies in lung cancer prevention.
关键词:pulmonary nodule;progression prediction;multimodal data fusion;criss-cross attention mechanism;directed graph neural network;high-risk lung cancer population;traditional Chinese and western clinical assessment
摘要:ObjectiveTo investigate the impacts of three types of acupuncture timing factors, including intervention initiation time, needle retention duration, and treatment intervals, on the treatment efficacy of ischemic stroke (IS) and provide evidence-based support for optimizing acupuncture timing strategies.MethodsA systematic search was conducted in both Chinese and English databases, including CNKI, Wanfang Data, VIP, CBM, PubMed, Web of Science, Cochrane Library, and Embase. The randomized controlled trials involving multiple acupuncture intervention time groups were included to reduce inter-study heterogeneity. A network meta-analysis model was constructed to compare the effects of different intervention initiation time, needle retention duration, and treatment intervals on primary IS outcomes, including total clinical response rate, neurological and limb function scores, quality of life score, and hemorheological parameters. Adverse events were also assessed.ResultsA total of 32 studies were included. The results showed that early acupuncture intervention (1-3 days and 4-7 days after onset) outperformed late intervention (>14 days) in terms of response rate, neurological function improvement, and quality of life (P<0.05, P<0.01). Extending needle retention time to 40-60 min was associated with improved response rates and hemorheological parameters (P<0.01). No significant differences were observed among different treatment intervals. The evidence of key outcomes showed high overall certainty, with low heterogeneity and inconsistency. Sensitivity analyses and publication bias assessments indicated the stability of the main results and a low risk of publication bias. No significant adverse reaction was reported.ConclusionDifferent timing factors significantly influence the efficacy of acupuncture treatment for IS. Early intervention and appropriately extended needle retention time result in better clinical outcomes, while treatment interval has no significant effect on efficacy. The inclusion of studies with multiple acupuncture timing groups helps control methodological heterogeneity and enhances the robustness of the analysis, providing evidence-based guidance for optimizing acupuncture timing strategies in IS management.
摘要:ObjectiveBased on the Huangdi Neijing,a traditional Chinese medicine(TCM)identification scale of five human qualities was constructed and applied in elderly people to evaluate its reliability and validity.MethodsBased on the original text of the Huangdi Neijing and a review of relevant ancient and modern literature, an identification scale of five human qualities was developed through Delphi expert interviews. Offline surveys were conducted to evaluate the feasibility,reliability,and validity of its application in elderly people,and the scale was evaluated and revised.ResultsThe scale of five human qualities is divided into five subscales:wood,fire,earth,metal,and water. Each subscale is divided into four dimensions:morphological structure,psychological characteristics,tolerance,and physiological characteristics,with a total of 75 items. The survey results in elderly people show that:(1) The recovery rate and completion rate are 100%,and the average filling time is 23.3 min. 85.5% of the samples are completed within the preset time. (2) Reliability analysis results:The homogeneity reliability of each subscale,Chronbach's α,ranges from 0.702 to 0.793. The scores of each subscale in the split-half reliability range from 0.758 to 0.841, indicating that the internal consistency of the scale is good. (3) Validity analysis results. Content validity:During the development stage of the scale,the item pool,dimensions,and structure of the scale are designed reasonably, and the content is complete. The evaluation of content validity shows that the item-level content validity index (I-CVI) ranges from 0.83 to 1.00, and the scale-level content validity index for universal agreement (S-CVI/UA) is 0.92,indicating good content validity of the scale. Construct validity extracts 22 common factors based on an eigenvalue of 1,with a contribution rate of 62.333% to the overall system. The number of common factors in the five subscales is 4,5,4,5,and 4,respectively,with contribution rates of 52.64%,53.376%,51.445%,51.359%,and 50.714%,respectively,indicating the required structure for physical fitness measurement in elderly people.ConclusionThe scale constructed in this study has high reliability and validity,and it is suitable for evaluating the physical condition of elderly people in TCM.
关键词:elderly people;five human qualities;constitution;reliability;validity
摘要:ObjectiveThe U6 promoter is an essential element for driving sgRNA expression in the clustered regularly interspaced short palindromic repeat sequences/CRISPR-associated protein 9(CRISPR/Cas9)gene editing system in dicotyledonous plants. Endogenous U6 promoters typically exhibit higher transcriptional activity, which can significantly improve gene editing efficiency. This study aims to identify endogenous U6 promoters in Artemisia annua to optimize its CRISPR/Cas9 gene editing system, which holds significant importance for its molecular breeding.MethodsOn the basis of the highly conserved U6 snRNA sequences in Arabidopsis thaliana, endogenous U6 promoters were screened in the A. annua genome. Expression vectors were constructed with candidate AaU6 promoter driving the firefly luciferase (LUC) reporter gene, and then transiently transformed into Nicotiana benthamiana. Transcriptional activities of the promoters were measured and compared by in vivo imaging and the Dual Luciferase Reporter assay.ResultsEight endogenous U6 promoters were successfully cloned from A. annua. Sequences alignment revealed that all these promoters contained the two conserved cis-acting elements, upstream sequence element (USE) and TATA-box, which affected their transcriptional activity. Dual-luciferase activity assays indicated that the transcriptional activities of AaU6-3, AaU6-1, and AaU6-5 were significantly higher than that of the Arabidopsis AtU6-26 promoter, with AaU6-3 exhibiting the highest activity.ConclusionThis study identified three endogenous AaU6 promoters with high transcriptional activity in A. annua, providing key functional elements for establishing an efficient gene editing system in A. annua. These findings will contribute to advancing precision molecular breeding and high-quality germplasm innovation in A. annua.
摘要:Qingzao Jiufeitang is a famous classical formula for treating lung injury caused by warm and dryness, included in the Catalogue of Ancient Famous Classical Formulas(The First Batch). By systematically organizing ancient and modern literature on this formula, this study analyzed and verified the origin, medicinal composition, original plants and processing, dosage and decoction method, efficacy and application of this formula. According to the research, Qingzao Jiufeitang was first recorded in Yimen Falyu in the Qing dynasty, and its creation was mainly inspired by the Ming dynasty physician MIAO Xiyong's idea of the moisturizing drugs with sweet flavour and cold nature. Based on the 2020 edition of the Pharmacopoeia of the People's Republic of China(hereinafter referred to as the Chinese Pharmacopoeia) and the textual research results of modern scholars on traditional Chinese herbal medicines, the botanical sources and processing methods of the herbs in this formula are basically clarified. Among them, Mori Folium, Gypsum Fibrosum, Ginseng Radix et Rhizoma, Sesami Semen Nigrum, Asini Corii Colla, Ophiopogonis Radix and Eriobotryae Folium are consistent with the 2020 edition of the Chinese Pharmacopoeia. The primary source of Glycyrrhizae Radix et Rhizoma is the dried roots and rhizomes of Glycyrrhiza uralensis, family Leguminosae, while the primary source of Armeniacae Semen Amarum is the dried mature seeds of Prunus armeniaca, family Rosaceae. It is recommended to use Gypsum Ustum, stir-fried Sesami Semen Nigrum, stir-fried Armeniacae Semen Amarum, Asini Corii Colla bead, and honey-fried Eriobotryae Folium, and the rest of the raw products. According to the conversion of ancient and modern doses, the recommended dosages are 11.19 g for Mori Folium, 9.33 g for Gypsum Fibrosum, 3.73 g for Glycyrrhizae Radix et Rhizoma, 2.61 g for Ginseng Radix et Rhizoma, 3.73 g for Sesami Semen Nigrum, 4.48 g for Ophiopogonis Radix, 2.61 g for Armeniacae Semen Amarum, 3.73 g for Eriobotryae Folium. The decoction method is to add 300 mL of water, decoct it down to 180 mL, remove the residue, and then add 2.98 g of Asini Corii Colla into the decoction. Take it warm after meals, two to three times a day. Qingzao Jiufeitang has the effects of clearing dryness and moistening the lungs, nourishing Yin and invigorating Qi. In ancient times, it was mainly used to treat stagnation and depression of various Qi, as well as paralysis, asthma and vomiting. In modern clinical practice, it is mostly used to treat diseases in respiratory system, otolaryngology, skin system and digestive system caused by warm-dry impairing lung, deficiency of both Qi and Yin. The above research results can provide a reference for the later development of Qingzao Jiufeitang.
关键词:famous classical formulas;Qingzao Jiufeitang;textual research;key information;ancient and modern application;origin;processing;decocting method
摘要:Qingfeitang, specialized in resolving phlegm to stop cough and producing fluid to moisten dryness, is a classic prescription inherited and developed by physicians of successive generations and has been included in the Catalogue of Ancient Classic Prescriptions (First Batch) published by the National Administration of Traditional Chinese Medicine (TCM) in 2018. Relevant ancient books data and modern literature were collected by bibliometrics to analyze the historic origin, formula composition, herb origin, preparation methods, processing methods, clinical effect, and indications of Qingfeitang. The key information of Qingfeitang was summarized to provide reference for the clinical application of the decoction. In this study, a total of 43 pieces of effective data on relevant ancient literature, including 35 ancient TCM books, were collected based on a systematic collation of relevant historic and modern literature. Results showed that "Qingfeitang" was originated from the "Renshen Qingfeitang" recorded in the Taiping Holy Prescriptions for Universal Relief from the Qing dynasty. The name of "Qinfeitang" was first recorded in the Yeshi Luyanfang written by YE Dalian in the Song dynasty. We suggested the modern dosage and usage of Qingfeitang as follows: "Scutellariae Radix of 5.60 g, Platycodon grandiflora, Poria, Tangerine, Fritillaria, and Cortex Mori of 3.73 g respectively, Angelicae Sinensis Radix, Asparagi Radix, Gardeniae Fructus, Armeniacae Semen Amarum, and Ophiopogonis Radix of 2.61 g respectively, Schisandra of 1 g, and Glycyrrhizae Radix et Rhizoma of 1.12 g, and they were taken 3 times daily. The above formula is recommended to be decocted with 400 mL of water, with 3.37 g ginger and 6 g jujubae fructus, to 320 mL, and taken after a meal, three times per day". Qingfeitang has the effect of resolving phlegm to stop cough and producing fluid to moisten dryness, specialized in treating cough, asthma, rash, and other symptoms in ancient times. Modern applications are mainly focused on the respiratory system, used for treating diseases such as bronchopneumonia and cough. The above research results provide a reference basis for the later development and research of Qingfeitang.
摘要:This article systematically analyzes the historical evolution of the name, origin, medicinal parts, harvesting, processing and others of Chrysanthemi Indici by referring to the herbal medicine, medical books, prescription books and other documents of the past dynasties, combined with the relevant modern research materials, in order to provide a basis for the development of famous classical formulas containing this medicinal herb. According to the research, Chrysanthemi Indici was first recorded under the name Kuyi in Bencao Jingjizhu, with aliases such as Yeshanju, Huangjuzai and Lubianju. The botanical source of Chrysanthemi Indici throughout history was Chrysanthemum indicum of the Asteraceae family. It is now distributed in most areas of China, and since the Qing dynasty, the product from Suichang, Zhejiang has been highly regarded. The whole plant can be used as medicine. According to the natural growth laws, the roots were collected in the first lunar month, leaves in the third, stems in the fifth, flowers in the ninth, and fruits in the eleventh, all of which were dried in the shade. In modern times, Chrysanthemi Indici is harvested during their initial blooming in autumn and winter. Since Bencao Gangmu listed Chrysanthemi Indici as a single medicinal material and clarified that all parts have medicinal value, ancient herbal texts began to record the independent medicinal use of Chrysanthemi Indici Flos, and the use of flowers as medicine has become mainstream. In modern times, the quality of Chrysanthemi Indici Flos is summarized to be best when they are dry, yellow, complete, and fragrant. Because Chrysanthemi Indici has a bitter and pungent taste, and is warm, it can eliminate and disperse, often using the power of alcohol to reach and ascend, and is commonly used to treat carbuncles, boils, and scrofula, with consistent properties and effects throughout ancient and modern times. Based on the research results, it is suggested that Chrysanthemi Indici involved in the formulas can be used as C. indicum, which can be used according to the medicinal parts labeled in the original formulas and the requirements of processing, while those without clear medicinal parts and requirements of processing should be used as the whole plant of the dried raw products.
关键词:famous classical formulas;Chrysanthemum indicum;origin;scientific name;medicinal parts;processing;herbal textual research
摘要:ObjectiveAccording to the etiology, pathogenesis, and clinical characteristics of dry eye (DE), this paper aims to analyze existing DE animal models to provide recommendations for building more clinically relevant DE models that integrate traditional Chinese and Western medicine.MethodsBy the retrieval and analysis of relevant literature on DE animal experiments, combined with expert consensus, an evaluation scale was created to assess relevance from the perspectives of pathogenesis, diagnostic criteria, and traditional Chinese medicine (TCM) differentiation. On the basis of data provided by the literature, the clinical relevance was evaluated for the animal models constructed in the literature.ResultsAmong the existing methods for establishing a DE animal model, benzalkonium chloride eye-drop induction showed the highest clinical relevance, demonstrating 98% alignment with Western medicine. However, current models generally showed higher relevance to Western medicine than to TCM, and there was a lack of models integrating disease with syndrome.ConclusionAs DE involves diverse causes and pathogenesis, single-factor models cannot fully simulate the complex pathology of DE. Future research should focus on building multi-mechanism DE models, exploring new etiological directions, standardizing model evaluation systems, and promoting integration of traditional Chinese and Western medicine. This will help precisely simulate the pathophysiological process of human DE and provide more valuable guidance for clinical diagnosis and treatment, ultimately enhancing patient outcomes and satisfaction.
关键词:dry eye;animal models;combination of disease and syndrome;characteristics of disease and syndrome
摘要:ObjectiveTo construct a comprehensive evaluation indicator system for clinical practice guidelines of traditional Chinese medicine (TCM) that is scientific, systematic, and reflects the characteristics of TCM.MethodsA systematic search was conducted in Chinese and English databases, including CNKI, Wanfang, VIP, SinoMed, PubMed, Embase, and Cochrane Library, to include literature on domestic and international guideline evaluation tools and TCM-related research. Document analysis and CiteSpace were utilized for keyword co-occurrence and clustering analysis.ResultsA total of 65 relevant studies were included, from which seven core thematic domains were identified. Based on the research objectives, a two-step construction strategy was adopted: first, an external evaluation framework was established by referencing international tools to cover methodological rigor and procedural standardization; second, an internal evaluation framework was developed to reflect the distinctive features of TCM clinical practice, including syndrome differentiation and efficacy feedback. Through expert consensus, the indicator system was refined, resulting in a dual-layered structure comprising 8 primary indicators, 22 secondary indicators, and 62 evaluation criteria.ConclusionThe comprehensive evaluation system for TCM clinical practice guidelines, based on bibliometric analysis and core element extraction, integrates both theoretical integrity and practical applicability. This study provides a preliminary research foundation for further optimization, validation, and development of a refined comprehensive evaluation system.
关键词:Traditional Chinese Medicine guidelines;literature analysis;quality appraisal;comprehensive evaluation
摘要:Traditional Chinese medicine (TCM) has long recognized metabolism-associated fatty liver disease (MASLD). The Classic of Difficulties (Nan Jing) records that "the accumulation of the liver is called obese Qi". ZHANG Jingyue also stated, "People with spleen and stomach deficiency and weakness or imbalance often suffer from diseases of accumulation". According to syndrome differentiation of the Zang-fu organs, modern physicians generally believe that the key pathogenesis of MASLD lies in the deficiency of spleen and stomach functions. However, MASLD is a chronic and complex disease, and its pathological characteristics cannot be fully explained by a single Zang-Fu syndrome differentiation. The concepts of sweat pores and collateral vessels emerged as early as the Huangdi's Internal Classic (Huang Di Nei Jing), and later TCM scholars, based on the idea that "sweat pore is the gateway of collateral vessels" proposed the concept of Xuanluo (sweat pores-collateral vessels). Xuanluo refers to fine structures widely distributed throughout the human body, serving as hubs and channels that regulate the movement and distribution of Qi, blood, and body fluids. By linking the Zang-Fu organs with Xuanluo, a theoretical framework of Qi, blood, and body fluid circulation centered on the "spleen and stomach-Xuanluo" as a whole was established, providing a new perspective for analyzing the essential pathogenesis of MASLD. Combined with the mechanisms involved in the formation and progression of MASLD, the intrinsic correlations between TCM pathogenesis and modern microscopic mechanisms are further analyzed. Modern studies have shown that intestinal microbial dysbiosis and mitochondrial dysfunction are pathological mechanisms involved in the occurrence and development of MASLD, but few have discussed the two as an integrated system. Existing research has confirmed that intestinal microorganisms can affect mitochondrial energy metabolism and oxidative stress through their metabolites, leading to hepatic energy metabolism disorders, oxidative stress (OS), and inflammation, thereby promoting MASLD progression. Focusing on the correspondence between the "spleen and stomach-Xuanluo" theory and the intestinal microorganism-mitochondrion micro-pathological mechanism, it is proposed that the spleen and stomach share similarities with intestinal microorganisms in the generation of Qi, blood, and body fluids as well as in the regulation of Qi movement, while Xuanluo and mitochondria have commonalities in energy regulation. Moreover, harmonizing the spleen and stomach to ensure unobstructed Xuanluo is the key to maintaining the normal interaction mechanism between intestinal microorganisms and mitochondria. Based on the correlation between the "spleen and stomach-Xuanluo" theory and the intestinal microorganism-mitochondrion interaction, this paper reveals that the essence of MASLD pathogenesis lies in spleen and stomach dysfunction, specifically, failure of the spleen to ascend the clear and failure of the stomach to descend the turbid, resulting in insufficient transformation of Qi and blood, impaired nourishment of Xuanluo, stagnation of Qi and blood, and the long-term formation of phlegm and blood stasis in the liver. Furthermore, it explores the preventive and therapeutic effects of tonifying the spleen and stomach, dredging Xuanluo and collaterals, unblocking the bowels, and regulating Qi in the treatment of MASLD, thereby providing new insights for its prevention and therapy.
关键词:metabolism-associated fatty liver disease;Xuanluo;spleen and stomach;intestinal microorganism;mitochondrial dysfunction
摘要:Non-small cell lung cancer (NSCLC), as the most common subtype of lung cancer, has a high incidence and mortality rate among global cancer cases. Although modern medicine has made remarkable progress in the treatment of NSCLC with advances in screening technologies and continuous optimization of therapeutic regimens, current treatments inevitably result in adverse outcomes such as high tumor recurrence rates, significant toxic side effects, and poor quality of life for patients. Traditional Chinese medicine (TCM) holds that the core pathogenesis of lung cancer lies in ''deficiency of healthy Qi and excess of pathogenic factors''. It originates from congenital insufficiency or acquired malnourishment, leading to an imbalance of Yin and Yang, deficiency of healthy Qi, and inability to eliminate pathogenic factors. The interactions among Qi stagnation, phlegm accumulation, blood stasis, and toxins give rise to disease. The root is deficiency, while the manifestation is excess. Therefore, the treatment of lung cancer in TCM is generally guided by the principle of "supporting the healthy Qi and eliminating the pathogens". A large number of clinical and pharmacological studies have shown that TCM and its active components can, through multiple targets and mechanisms, alleviate postoperative and chemoradiotherapy-related adverse reactions, inhibit tumor growth and recurrence, and improve the quality of life of patients with NSCLC. It is worth noting that although extensive studies have been conducted on the therapeutic patterns and pharmacological mechanisms of TCM and its active substances in NSCLC treatment, issues such as the diversity of medicinal materials, the complexity of chemical components, the scientific basis of herbal compatibility, and the flexibility of dosage indicate that there is still considerable room for further clinical and basic research. This review summarizes recent literature on the clinical syndromes, drug selection, medication patterns, and pharmacological mechanisms of TCM and its active components in the treatment of NSCLC, aiming to provide guidance for clinical medication in TCM therapy for NSCLC and to deepen the understanding and research of its therapeutic mechanisms.
关键词:traditional Chinese medicine;non-small cell lung cancer;clinical syndromes;drug selection;medication patterns;pharmacological mechanisms
摘要:In recent years, as the incidence of ulcerative colitis (UC) is growing, intestinal mucosal injury has garnered increasing attention, and it is characterized by high recurrence, risk of inflammation-cancer transformation, and difficulty in repair. Intestinal mucosal injury in UC is centered on persistent inflammation and barrier dysfunction, with its pathological mechanisms involving endoplasmic reticulum stress (ERS)-mediated changes such as abnormal apoptosis, abnormal autophagy, and inflammatory responses. ERS induces apoptosis of intestinal epithelial cells, disrupts tight junction proteins, and exacerbates inflammatory responses through pathways such as protein kinase R-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1 alpha (IRE1α), and activating transcription factor 6 (ATF6), ultimately causing intestinal mucosal injury. Traditional Chinese medicine (TCM) has a long history of research on UC. The theory of sores depending on spleen-earth holds that spleen deficiency is the fundamental cause of UC, while pathological products such as dampness-turbidity and blood stasis are the secondary manifestations. Dysfunction of the spleen-earth leads to insufficient production and transformation of Qi and blood, malnutrition of the intestinal mucosa, and invasion of external pathogens. In the active phase of UC, spleen deficiency is often accompanied by excessive pathogenic factors such as dampness-heat and heat-toxin, leading to acute intestinal mucosal damage. In the remission phase, however, it is mainly characterized by spleen deficiency and healthy Qi deficiency, accompanied by residual pathogens, resulting in weak intestinal mucosal repair. Studies have shown that the endoplasmic reticulum, as a key site for protein synthesis and folding, has functions highly similar to the TCM concept of the spleen governing transportation and transformation. From a TCM perspective, the endoplasmic reticulum can be regarded as the carrier of spleen transportation, and ERS is a microcosmic manifestation of spleen dysfunction, leading to intestinal mucosal injury. ERS impairs the structure and function of the endoplasmic reticulum, induces the generation of abnormal Qi, and triggers pathological changes, making inflammation difficult to be reduced and causing the aggravation of ERS, forming a vicious cycle of spleen deficiency-pathological products-intestinal injury. TCM has unique advantages in regulating ERS to prevent and treat intestinal mucosal injury. According to the theory of sores depending on spleen-earth and the modern medical understanding of ERS, this paper delves into the TCM and Western medicine pathogenesis of intestinal mucosal injury in UC. Furthermore, this paper discusses the roles of TCM active components and compound formulas in reducing intestinal mucosal injury in UC by regulating ERS under the guidance of the treatment principles of invigorating the spleen and replenishing Qi as the key and dispelling dampness and removing blood stasis as the supplementation, aiming to provide new ideas and methods for the prevention and treatment of UC.
关键词:ulcerative colitis;endoplasmic reticulum stress;intestinal mucosa;sores depending on spleen-earth;traditional Chinese medicine
摘要:As a common medical condition, vertigo can be induced by multiple diseases in the modern medical system. Its incidence rate shows an upward trend with the increase in age. According to the theory of mutual interference between clear Qi and turbid Qi in Huangdi's Internal Classic (Huang Di Nei Jing), this paper systematically analyzes the pathogenesis of vertigo and explores the mechanism and clinical application value of Xiao Chaihutang in the treatment of vertigo. It is believed that the mutual inference between clear Qi and turbid Qi leads to the failure of clear Yang to ascend, resulting in the lack of nourishment for the brain and the inability of turbid Yin to descend, which disturbs the clear orifices, thus causing vertigo. The core pathogenesis lies in the dysfunction of Qi movement, the disorder of body fluid distribution, and the imbalance between Yin and Yang. The compatibility of Xiao Chaihutang takes into account the methods of pungent medicinal materials opening and bitter medicinal materials descending, tonifying deficiency and purging excess, and regulating Qi movement. This prescription can regulate the pathological state of the mutual interference between clear Qi and turbid Qi from three aspects: regulating Qi movement throughout the body, harmonizing the distribution of body fluids, and coordinating Yin and Yang as well as the interior and exterior, thus preventing and treating vertigo. Modern research findings show that Xiao Chaihutang can improve hemodynamics to promote cerebral blood circulation and has anti-inflammation, immunomodulatory, and anti-tumor functions, which correspond to the therapeutic effects of Xiao Chaihutang under the theory of mutual interference between clear Qi and turbid Qi. The decoction exerts therapeutic effects on vertigo caused by hypertension, stroke, otitis media, Meniere’s disease, and brain tumor as well as benign paroxysmal positional vertigo. Further exploration of the theoretical connotation of mutual inference between clear Qi and turbid Qi and analysis of the pathogenesis of vertigo and the therapeutic effect of Xiao Chaihutang can better interpret the internal correlations among the three, thus providing new ideas for the syndrome differentiation and treatment of vertigo.
关键词:mutual inference between clear Qi and turbid Qi;vertigo;Xiao Chaihutang;Huangdi's Internal Classic (Huang Di Nei Jing);theoretical exploration
摘要:Xiao Chaihutang, originating from the Treatise on Typhoid and Miscellaneous Diseases, is a classic formula for harmonizing the Shaoyang. It excels in regulating the pivotal mechanism and unblocking the triple energizer, corresponding to the pathogenesis of digestive system tumors characterized by the interlocking of deficiency, stasis, phlegm, and toxicity, as well as disharmony between Yin and Yang. This paper systematically reviews research findings from China and abroad over the past decade, exploring the anti-tumor effects of Xiao Chaihutang on digestive system tumors from three dimensions: theoretical rationale, clinical efficacy, and molecular mechanisms. At the level of principle and method, Xiao Chaihutang takes "harmonization" as its core therapeutic guideline. By reconciling the exterior and interior to restore the Shaoyang pivot, harmonizing Yin and Yang to improve the tumor microenvironment, and regulating the liver and spleen to consolidate and protect the foundation of postnatal essence, it promotes the restoration of the body's dynamic balance of Yin and Yang. Clinical studies have demonstrated that Xiao Chaihutang, used alone or in combination with modern medical therapies, shows definite efficacy against digestive system tumors such as hepatocellular carcinoma, pancreatic carcinoma, and gastrointestinal carcinoma. It can significantly improve patients' quality of life, inhibit tumor progression, effectively relieve concomitant symptoms such a s cancer-related fever, anxiety, depression, and insomnia, and alleviate postoperative embolic syndromes as well as adverse reactions to radiotherapy and chemotherapy. Experimental studies have revealed that Xiao Chaihutang can inhibit tumor cell proliferation, induce apoptosis, arrest the cell cycle, suppress tumor cell invasion and metastasis, and improve the tumor microenvironment. Through the above analysis, this study elucidates the current clinical and experimental research status of Xiao Chaihutang in the treatment of digestive system tumors, aiming to provide theoretical support for its precise clinical application. On this basis, it further explores key issues in the identification of pharmacodynamic substances and the accumulation of evidence in evidence-based medicine, thereby offering a new perspective for the innovative development of integrative Chinese and Western medicine in synergistic cancer therapy.
关键词:Xiao Chaihutang;digestive system tumors;review;clinical application;mechanism of action
摘要:Lung cancer has the highest morbidity and mortality rate among all cancers. Because of the complex pathogenesis, there are limitations in the common Western medicine treatment methods. Clinical and experimental studies have proved that traditional Chinese medicine (TCM) can not only effectively treat lung cancer and alleviate the clinical symptoms of cancer patients but also reduce the adverse reactions and complications caused by surgery, chemotherapy, and radiotherapy to improve the quality of life of the patients. The biological behaviors of lung cancer cells, such as proliferation, invasion, and metastasis, are closely related to their metabolic reprogramming. Metabolic reprogramming in lung cancer involves a series of metabolic changes such as increased glucose uptake and consumption, enhanced glycolysis, increased amino acid uptake and catabolism, and enhanced lipid and protein synthesis. Studies have reported that TCM active components, extracts, and compound prescriptions can effectively inhibit the biological behaviors of lung cancer by regulating metabolic reprogramming. Therefore, this paper reviews the pharmacological mechanisms of TCM active components, extracts, and compound prescriptions in regulating metabolic reprogramming of lung cancer, with the aim of providing a new way of thinking for the treatment of lung cancer by TCM regulation of metabolic reprogramming of lung cancer cells. The available studies suggest that TCM mainly inhibits the extracellular signal-regulated protein kinase (ERK)/c-Myc, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), and hypoxia-inducible factor-α (HIF-1α) pathways. Furthermore, the expression of monocarboxylate transporter 4 (MCT4), glucose transporter 1 (GLUT1), pyruvate dehydrogenase (PDH), phosphofructokinase 1 (PFK1), pyruvate dehydrogenase kinase 1 (PDK1), pyruvate kinase M2 (PKM2), hexokinase (HK), lactate dehydrogenase (LDH), and lactate dehydrogenase A (LDHA) are inhibited. In this way, TCM inhibits the glucose uptake by lung cancer cells and glycolysis in lung cancer cells to reduce the energy metabolism of tumor cells, ultimately achieving the therapeutic effect on lung cancer.
关键词:traditional Chinese medicine;regulation;metabolic reprogramming;lung cancer;research progress
摘要:Gastrointestinal tumors (GTs), including colorectal cancer, gastric cancer, liver cancer, pancreatic cancer, and esophageal cancer, are increasing in incidence worldwide and have become one of the major diseases threatening human health. Tumor stem cells (TSCs), an undifferentiated subpopulation within tumor tissues, possess biological characteristics such as self-renewal, multidirectional differentiation, high tumorigenicity, and resistance to radiochemotherapy. They play an important role in the occurrence, progression, recurrence, and metastasis of GTs and have increasingly become a research hotspot in GT treatment. Although modern medicine has made remarkable progress, there remain many problems in therapeutic approaches targeting TSCs. In this context, traditional Chinese medicine (TCM), with its favorable safety profile and multi-target mechanisms, has shown potential advantages and value in regulating TSCs. It can reduce TSC drug resistance, enhance the sensitivity of tumor cells to chemotherapeutic agents, inhibit tumor growth and metastasis, and has shown unique advantages in improving the quality of life and prolonging the survival of GT patients. Studies have found that active components of Chinese medicine, such as terpenoids, polyphenols, flavonoids, glycosides, and quinones, and Chinese medicine compound formulas, including Zuojin pills, Sijunzi decoction, Biejiajian pills, and Xuanfu Daizhe decoction, can inhibit TSCs-related signaling pathways such as the Notch signaling pathway, the Wnt/β-catenin signaling pathway, the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway, and the Hippo signaling pathway. They also reduce the expression of TSC surface markers, including sex-determining region Y-box 2 (SOX2), sex-determining region Y-box 9 (SOX9), octamer-binding transcription factor 4 (OCT4), prominin-1 (CD133), cluster of differentiation 44 (CD44), cluster of differentiation 24 (CD24), and thyroid transmembrane protein 1 (CD90), thereby hindering TSC differentiation, accelerating their metabolic processes, improving the tumor microenvironment, and consequently inhibiting GT growth. This study collects and analyzes recent research on the regulation of TSCs by TCM in the treatment of GT, aiming to provide a new theoretical basis for tumor therapy with TCM, expand its application in the comprehensive treatment of GT, and offer new therapeutic ideas and methods for clinical practice.
关键词:active ingredients of Chinese medicine;Chinese medicine compound formulas;tumor stem cells;gastrointestinal tumor;mechanism study
摘要:Diabetic kidney disease (DKD) stands as one of the most prevalent microvascular complications of diabetes,noted for its concealed onset and tendency to evolve into end-stage renal disease,profoundly impacting patients' life expectancy and quality of life. Epithelial-to-mesenchymal transition (EMT) is a central pathological process in the initiation and progression of DKD,facilitating disease advancement and renal fibrosis,thus representing a crucial focus of research into the pathological mechanisms of DKD. EMT is driven by the abnormal activation of signaling pathways,including transforming growth factor-β (TGF-β)/Smad,secreted glycoprotein/β-catenin,Notch,tumor necrosis factor-α (TNF-α)/nuclear factor-κB (NF-κB),and phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR),leading to renal cellular injury and subsequently accelerating renal fibrosis and the progression of DKD. Traditional Chinese medicine (TCM),characterized by its multi-target and multi-pathway therapeutic approach,demonstrates unique advantages in addressing DKD and EMT. Recent research has shown that active ingredients in TCM,including glycosides,flavonoids,and polyphenols,as well as TCM formulas,can precisely target these relevant signaling pathways,effectively inhibiting cellular injury in DKD and intervening in the EMT process. These findings not only underscore the potential of TCM monomers and formulas in treating DKD and EMT but also pave new directions for research in this field within TCM. This paper systematically reviewed the signaling pathways associated with EMT and provided an in-depth analysis of the research achievements and underlying mechanisms of TCM monomers and formulas in treating DKD and intervening in EMT,aiming to offer new insights and directions for TCM in the treatment of DKD and research on EMT,thereby further promoting the modernization and development of TCM.
关键词:diabetic kidney disease;epithelial-mesenchymal transition;signaling pathway;traditional Chinese medicine;mechanism research