ObjectiveTo investigate the epigenetic mechanism of Diwu Yanggan Capsule in improving liver regeneration microenvironment in a rat model of liver cancer by regulating DNA methylation， and to provide a basis for scientific clinical medication. MethodsA total of 48 specific pathogen-free Sprague-Dawley rats were divided into normal group， model group， and Diwu Yanggan Capsule group using a random number table， with 16 rats in each group. The Solt-Farber two-step method was used to establish a rat model of liver cancer. The rats in the Diwu Yanggan Capsule group were given Diwu Yanggan Capsule at a dose of 750 mg/kg/d by gavage， and those in the normal group and the model group were given an equal volume of normal saline by gavage. Liver tissue samples were collected from each group of rats after 16 weeks of continuous intervention； DNA methylation chips were used to analyze the change in DNA methylation in liver tissue， and gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses were used for data analysis. In addition， the MeDIP-PCR technique was used to detect the changes in candidate differentially methylated genes such as YWHAB， ADCK2， ERLIN2， SEMA3B， and TPH2 in the liver tissue of rats， and Western blot and RT-qPCR were used to verify the expression of key methylated genes. The independent-samples t test was used for comparison of continuous data between two groups， and a one-way analysis of variance was used for comparison between multiple groups， while the least significant difference t-test was used for further comparison between two groups. ResultsThe DNA methylation chip analysis showed that compared with the normal group， the model group had significant methylation changes in the promoter region of 2 422 genes in liver tissue of rats. The GO functional enrichment analysis and the KEGG pathway enrichment analysis showed that these differentially methylated genes were significantly enriched in metabolic pathways such as steroid hormone biosynthesis and drug metabolism-cytochrome P450. Compared with the model group， the Diwu Yanggan Capsule group had significant reversal of promoter methylation in 1 650 genes， and the KEGG enrichment analysis showed that these genes were mainly involved in the pathways closely associated with cell proliferation， apoptosis， and microenvironment regulation， such as the calcium ion signaling pathway， the cAMP signaling pathway， and the extracellular factor signaling pathway. Compared with the model group， the Diwu Yanggan Capsule group had a significant increase in the promoter methylation level of the ADCK2 gene （P<0.05） and significant reductions in the promoter methylation levels of the ERLIN2 and TPH2 genes （all P<0.05）. Compared with the model group， the Diwu Yanggan Capsule group had significant reductions in the mRNA expression levels and the protein expression levels of the ADCK2 （all P<0.05）. ConclusionAbnormal DNA methylation in liver tissue participates in the development and progression of liver cancer. The effect of Diwu Yanggan Capsule on DNA methylation level is an important epigenetic mechanism for its effect in the prevention and treatment of liver cancer.

BACKGROUND:Although previous studies have reported associations between lipids and the risk of osteoporotic pathological fractures,the specific causal relationships between lipid level and osteoporotic pathological fractures remain unclear.OBJECTIVE:To elucidate the causal relationship between lipids and osteoporotic pathological fractures using a two-sample bidirectional Mendelian randomization analysis.METHODS:The data for 178 lipid metabolites were obtained from the IEU-GWAS database(developed by the MRC Integrative Epidemiology Unit at the University of Bristol,UK,which provides extensive summary data from genome-wide association studies),while osteoporotic pathological fracture data(from 173 619 European participants)were acquired from the FinnGen database(constructed by the Finnish national gene research program,focusing on investigating relationships between genomics and health/disease in the Finnish population).Osteoporotic pathological fracture data were used as the outcome variable,with lipids serving as exposures,for the bidirectional Mendelian randomization study to evaluate the causal effects of different lipids on osteoporotic pathological fractures.The UK Biobank database was employed as a validation set by switching the outcome variable to verify the findings horizontally.RESULTS AND CONCLUSION:(1)The inverse variance weighted analysis indicated that each unit increase in sterol ester(27∶1/20∶2)levels was associated with a 25.55％increase in the risk of osteoporotic pathological fractures(odds ratio=1.256,95％confidence interval:1.001-1.575,P=0.049),suggesting a significant positive correlation between elevated sterol ester levels and increased fracture risk.Reverse Mendelian randomization analysis revealed a significant negative association between osteoporotic pathological fractures and three types of phosphatidylcholine.Horizontal validation yielded consistent results,confirming sterol ester as a risk factor for osteoporotic pathological fractures.(2)The results indicate that sterol ester is a risk factor for osteoporotic pathological fractures,while phosphatidylcholine serves as a protective factor.These findings strengthen the evidence supporting the effect of lipids on the risk of osteoporotic pathological fractures.Although the GWAS data used in this study were derived from European populations,given the broad commonality of human genetics,the results provide valuable reference significance for improving osteoporosis in Chinese populations through lipid regulation.

BACKGROUND:Although previous studies have reported associations between lipids and the risk of osteoporotic pathological fractures,the specific causal relationships between lipid level and osteoporotic pathological fractures remain unclear.OBJECTIVE:To elucidate the causal relationship between lipids and osteoporotic pathological fractures using a two-sample bidirectional Mendelian randomization analysis.METHODS:The data for 178 lipid metabolites were obtained from the IEU-GWAS database(developed by the MRC Integrative Epidemiology Unit at the University of Bristol,UK,which provides extensive summary data from genome-wide association studies),while osteoporotic pathological fracture data(from 173 619 European participants)were acquired from the FinnGen database(constructed by the Finnish national gene research program,focusing on investigating relationships between genomics and health/disease in the Finnish population).Osteoporotic pathological fracture data were used as the outcome variable,with lipids serving as exposures,for the bidirectional Mendelian randomization study to evaluate the causal effects of different lipids on osteoporotic pathological fractures.The UK Biobank database was employed as a validation set by switching the outcome variable to verify the findings horizontally.RESULTS AND CONCLUSION:(1)The inverse variance weighted analysis indicated that each unit increase in sterol ester(27∶1/20∶2)levels was associated with a 25.55％increase in the risk of osteoporotic pathological fractures(odds ratio=1.256,95％confidence interval:1.001-1.575,P=0.049),suggesting a significant positive correlation between elevated sterol ester levels and increased fracture risk.Reverse Mendelian randomization analysis revealed a significant negative association between osteoporotic pathological fractures and three types of phosphatidylcholine.Horizontal validation yielded consistent results,confirming sterol ester as a risk factor for osteoporotic pathological fractures.(2)The results indicate that sterol ester is a risk factor for osteoporotic pathological fractures,while phosphatidylcholine serves as a protective factor.These findings strengthen the evidence supporting the effect of lipids on the risk of osteoporotic pathological fractures.Although the GWAS data used in this study were derived from European populations,given the broad commonality of human genetics,the results provide valuable reference significance for improving osteoporosis in Chinese populations through lipid regulation.

Moyamoya vasculopathy (MMV) refers to a chronic cerebrovascular disease characterized by progressive stenosis or occlusion of the arteries around the circle of Willis, accompanied by the formation of collateral vessels. In traditional Chinese medicine (TCM), MMV falls into the categories of “stroke”, “vertigo”, and “headache”, among others. Its core etiology is related to congenital insufficiency and acquired malnourishment, with wind, fire, phlegm, deficiency, and stasis as the key pathogenic factors. Current Western medical diagnosis and treatment of MMV remain suboptimal, and TCM pattern differentiation has yet to be standardized. The most common clinical patterns are liver yang hyperactivity (associated with hemorrhagic symptoms) and qi deficiency with blood stasis (associated with ischemic symptoms). Treatment modalities include acupuncture, Chinese herbal formulas, and TCM–Western medicine integrated therapy. Clinical trial results have confirmed that integrated therapy offers certain benefits for MMV; however, there is a lack of relevant diagnostic and treatment guidelines as well as in-depth mechanistic studies. This article reviews the progress in TCM and Western medicine for the diagnosis and treatment of MMV and proposes a trinity diagnostic and therapeutic approach integrating “disease differentiation–pattern differentiation–staging”, which provides a reference for TCM–Western medicine integration management.

Dietary guidelines are nutritional policy tools formulated according to the global consensus on nutrition science and national conditions. Based on five core consensuses, namely dietary patterns, food group recommendations, full life cycle coverage, policy attributes, and sustainable diets, this paper reviews the scientific validity and applicability of the Dietary Guidelines for Americans, 2025-2030. With “Eat Real Food” as its core concept, this guideline has adjusted its food recommendations, population-specific guidance, and policy implementation pathways. However, some of its scientific evidence such as protein and fat recommendations is controversial, and the feasibility of its implementation is fraught with challenges. Rationally reflecting on the practical experience from the U.S., we suggest the revision of the Dietary Guidelines for Chinese Residents should optimize the dietary guidance system based on national conditions, and promote the policy transformation and practical application.

Ferroptosis, a programmed cell death modality discovered and defined in the last decade, is primarily induced by iron-dependent lipid peroxidation. At present, it has been found that ferroptosis is involved in various physiological functions such as immune regulation, growth and development, aging, and tumor suppression. Especially its role in tumor biology has attracted extensive attention and research. Breast cancer is one of the most common female tumors, characterized by high heterogeneity and complex genetic background. Triple negative breast cancer (TNBC) is a special type of breast cancer, which lacks conventional breast cancer treatment targets and is prone to drug resistance to existing chemotherapy drugs and has a low cure rate after progression and metastasis. There is an urgent need to find new targets or develop new drugs. With the increase of studies on promoting ferroptosis in breast cancer, it has gradually attracted attention as a treatment strategy for breast cancer. Some studies have found that certain compounds and natural products can act on TNBC, promote their ferroptosis, inhibit cancer cells proliferation, enhance sensitivity to radiotherapy, and improve resistance to chemotherapy drugs. To promote the study of ferroptosis in TNBC, this article summarized and reviewed the compounds and natural products that induce ferroptosis in TNBC and their mechanisms of action. We started with the exploration of the pathways of ferroptosis, with particular attention to the System X_c^--cystine-GPX4 pathway and iron metabolism. Then, a series of compounds, including sulfasalazine (SAS), metformin, and statins, were described in terms of how they interact with cells to deplete glutathione (GSH), thereby inhibiting the activity of glutathione peroxidase 4 (GPX4) and preventing the production of lipid peroxidases. The disruption of the cellular defense against oxidative stress ultimately results in the death of TNBC cells. We have also our focus to the realm of natural products, exploring the therapeutic potential of traditional Chinese medicine extracts for TNBC. These herbal extracts exhibit multi-target effects and good safety, and have shown promising capabilities in inducing ferroptosis in TNBC cells. We believe that further exploration and characterization of these natural compounds could lead to the development of a new generation of cancer therapeutics. In addition to traditional chemotherapy, we discussed the role of drug delivery systems in enhancing the efficacy and reducing the toxicity of ferroptosis inducers. Nanoparticles such as exosomes and metal-organic frameworks (MOFs) can improve the solubility and bioavailability of these compounds, thereby expanding their therapeutic potential while minimizing systemic side effects. Although preclinical data on ferroptosis inducers are relatively robust, their translation into clinical practice remains in its early stages. We also emphasize the urgent need for more in-depth and comprehensive research to understand the complex mechanisms of ferroptosis in TNBC. This is crucial for the rational design and development of clinical trials, as well as for leveraging ferroptosis to improve patient outcomes. Hoping the above summarize and review could provide references for the research and development of lead compounds for the treatment for TNBC.

Objective To investigate the effect and mechanism of miglitol on regulating the energy metabolism of brown adipocytes by activating UCP1 and preventing cold injury in mice after cold exposure. Methods Primary brown adipocytes were induced into mature adipocytes, the effect of miglitol on the viability of brown adipocytes was investigated by MTT method, the lipid droplet consumption level of cells after drug administration was investigated by Oil Red O staining technology, and the level of UCP1, a key protein of thermogenesis in brown adipocytes, was detected by Western blotting. The activity of anti-frostbite was investigated in cold exposure at 4 ℃ and −20 ℃. KM mice, which were randomly divided into control group, cold exposure group, miglitol group and all-trans retinoic acid group, and after 7 days of repeated administration, the body surface temperature of mice was detected by infrared thermal imaging system, the anal temperature change was detected by anal thermometer, and the expression levels of UCP1 and PGC1-α in adipose tissue were detected by immunoblotting. Results Compared with the control group, the lipid droplet consumption and UCP1 expression levels in brown adipocytes in the miglitol group were significantly increased. The levels of body surface temperature and rectal temperature increased significantly after cold exposure, and the levels of UCP1 and PGC1α in the brown adipose tissue of mice increased significantly, which indicated that the miglitol could activate the critical proteins UCP1 and PGC1α of the thermogenesis pathway, increase the thermogenesis of mice after cold exposure, and thus improve the effect of cold injury for toe swelling. Conclusion Miglitol could play a role in improving cold injury and body temperature in mice by increasing the level of UCP1 and PGC1α, which are key targets of the thermogenesis pathway to promote the thermogenesis of brown fat.

OBJECTIVE: To explore the role of the natural compound hesperidin in glycolysis, the key ratelimiting enzyme, in colorectal cancer (CRC) cell lines. METHODS: In vitro, HCT116 and SW620 were treated with different doses of hesperidin (0-500 µmol/L), cell counting kit-8 and colone formation assays were utilized to detected inhibition effect of hesperidin on CRC cell lines. Transwell and wound healing assays were performed to detect the ability of hesperidin (0, 25, 50 and 75 µmol/L) to migrate CRC cells. To confirm the apoptotic-inducing effect of hesperidin, apoptosis and cycle assays were employed. Western blot, glucose uptake, and lactate production determination measurements were applied to determine inhibitory effects of hesperidin (0, 25 and 50 µmol/L) on glycolysis. In vivo, according to the random number table method, nude mice with successful tumor loading were randomly divided into vehicle, low-dose hesperidin (20 mg/kg) and high-dose hesperidin (60 mg/kg) groups, with 6 mice in each group. The body weights and tumor volumes of mice were recorded during 4-week treatment. The expression of key glycolysis rate-limiting enzymes was determined using Western blot, and glucose uptake and lactate production were assessed. Finally, protein interactions were probed with DirectDIA Quantitative Proteomics, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. RESULTS: Hesperidin could inhibit CRC cell line growth (P<0.05 or P<0.01). Moreover, hesperidin presented an inhibitory effect on the migrating abilities of CRC cells. Hesperidin also promoted apoptosis and cell cycle alterations (P<0.05). The immunoblotting results manifested that hesperidin decreased the levels of hexokinase 2, glucose transporter protein 1 (GLUT1), GLUT3, L-lactate dehydrogenase A, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), PFKFB3, and pyruvate kinase isozymes M2 (P<0.01). It remarkably suppressed tumor xenograft growth in nude mice. GO and KEGG analyses showed that hesperidin treatment altered metabolic function. CONCLUSION Hesperidin inhibits glycolysis and is a potential therapeutic choice for CRC treatment.
Hesperidin/therapeutic use* ; Colorectal Neoplasms/metabolism* ; Glycolysis/drug effects* ; Animals ; Humans ; Apoptosis/drug effects* ; Mice, Nude ; Cell Movement/drug effects* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Glucose/metabolism* ; Cell Cycle/drug effects* ; Mice, Inbred BALB C ; Mice ; HCT116 Cells ; Lactic Acid

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies