From the perspective of competitive endogenous RNA(ceRNA) constructed by metastasy-associated lung adenocarcinoma transcript 1(Malat1) and microRNA 16-5p(miR-16-5p), the improvement mechanism of Tonggu Xiaotong Capsules(TGXTC) on the imbalance and disorder of "cholesterol-iron" metabolism in chondrocytes of osteoarthritis(OA) was explored. In vivo experiments, 60 8-week-old C57BL/6 mice were acclimatized and fed for 1 week and then randomly divided into two groups: blank group(12 mice) and modeling group(48 mice). The animals in modeling group were anesthetized by 5% isoflurane inhalation, which was followed by the construction of OA model. They were then randomly divided into model group, TGXTC group, Malat1 overexpression group, and TGXTC+Malat1 overexpression(TGXTC+Malat1-OE) group, with 12 mice in each group. The structural changes of mouse cartilage tissues were observed by Masson staining after the intervention in each group. RT-PCR was employed to detect the mRNA levels of Malat1 and miR-16-5p in cartilage tissues. Western blot was used to analyze the protein expression of ATP-binding cassette transporter A1(ABCA1), sterol regulatory element-binding protein(SREBP), cytochrome P450 family 7 subfamily B member 1(CYP7B1), CCAAT/enhancer-binding protein homologous protein(CHOP), acyl-CoA synthetase long-chain family member 4(ACSL4), and glutathione peroxidase 4(GPX4) in cartilage tissues. In vitro experiments, mouse chondrocytes were induced by thapsigargin(TG), and the combination of Malat1 and miR-16-5p was detected by double luciferase assay. The fluorescence intensity of Malat1 in chondrocytes was determined by fluorescence in situ hybridization. The miR-16-5p inhibitory chondrocyte model was constructed. RT-PCR was used to analyze the levels of Malat1 and miR-16-5p in chondrocytes under the inhibition of miR-16-5p. Western blot was adopted to analyze the regulation of TG-induced chondrocyte proteins ABCA1, SREBP, CYP7B1, CHOP, ACSL4, and GPX4 by TGXTC under the inhibition of miR-16-5p. The results of in vivo experiments showed that,(1) compared with model group, TGXTC group exhibited a relatively complete cartilage layer structure. Compared with Malat1-OE group, TGXTC+Malat1-OE group showed alleviated cartilage surface damage.(2) Compared with model group, TGXTC group had a significantly decreased Malat1 mRNA level and an increased miR-16-5p mRNA level in mouse cartilage tissues(P<0.01).(3) Compared with the model group, the protein levels of ABCA1 and GPX4 in the cartilage tissue of mice in the TGXTC group increased, while the protein levels of SREBP, CYP7B1, CHOP and ACSL4 decreased(P<0.01). The results of in vitro experiments show that,(1) dual-luciferase was used to evaluate that miR-16-5p has a targeting effect on the Malat1 gene.(2)Compared with TG+miR-16-5p inhibition group, TG+miR-16-5p inhibition+TGXTC group had an increased mRNA level of miR-16-5p and an decreased mRNA level of Malat1(P<0.01).(3) Compared with TG+miR-16-5p inhibition group, TG+miR-16-5p inhibition+TGXTC group exhibited increased expression of ABCA1 and GPX4 proteins and decreased expression of SREBP, CYP7B1, CHOP, and ACSL4 proteins(P<0.01). The reasults showed that TGXTC can regulate the ceRNA of Malat1 and miR-16-5p to alleviate the "cholesterol-iron" metabolism disorder of osteoarthritis chondrocytes.
Animals ; MicroRNAs/metabolism* ; RNA, Long Noncoding/metabolism* ; Chondrocytes/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Mice, Inbred C57BL ; Mice ; Osteoarthritis/drug therapy* ; Iron/metabolism* ; Male ; Cholesterol/metabolism* ; Humans ; Capsules ; RNA, Competitive Endogenous

OBJECTIVE: Several epidemiological observational studies have related particulate matter (PM) exposure to Inflammatory bowel disease (IBD), but many confounding factors make it difficult to draw causal links from observational studies. The objective of this study was to explore the causal association between PM _2.5 exposure, its absorbance, and IBD. METHODS: We assessed the association of PM _2.5 and PM _2.5 absorbance with the two primary forms of IBD (Crohn's disease [CD] and ulcerative colitis [UC]) using Mendelian randomization (MR) to explore the causal relationship. We conducted two-sample MR analyses with aggregated data from the UK Biobank genome-wide association study. Single-nucleotide polymorphisms linked with PM _2.5 concentrations or their absorbance were used as instrumental variables (IVs). We used inverse variance weighting (IVW) as the primary analytical approach and four other standard methods as supplementary analyses for quality control. RESULTS: The results of MR demonstrated that PM _2.5 had an adverse influence on UC risk (odds ratio [ OR] = 1.010; 95% confidence interval [ CI] = 1.001-1.019, P = 0.020). Meanwhile, the results of IVW showed that PM _2.5 absorbance was also causally associated with UC ( OR = 1.012; 95% CI = 1.004-1.019, P = 0.002). We observed no causal relationship between PM _2.5, PM _2.5 absorbance, and CD. The results of sensitivity analysis indicated the absence of heterogeneity or pleiotropy, ensuring the reliability of MR results. CONCLUSION Based on two-sample MR analyses, there are potential positive causal relationships between PM _2.5, PM _2.5 absorbance, and UC.
Humans ; Mendelian Randomization Analysis ; Particulate Matter/analysis* ; Polymorphism, Single Nucleotide ; Inflammatory Bowel Diseases/genetics* ; Air Pollutants/analysis* ; Crohn Disease/genetics* ; Colitis, Ulcerative/genetics* ; Genome-Wide Association Study ; Risk Factors ; Environmental Exposure

Banxia Xiexin Decoction has the effect of harmonizing the spleen and stomach,and regulating cold and heat.It is mainly used for the treatment of epigastric fullness of mixed cold and heat in the heart,and has certain advantages in relieving symptoms,reducing recurrence rates,and ensuring safety.This article reviewed the clinical application of Banxia Xiexin Decoction from the perspectives of digestive system diseases,neurological diseases,gastrointestinal tumors,respiratory system diseases,endocrine diseases,dermatological diseases,gynecological diseases,and other diseases.It also summarized the mechanism of Banxia Xiexin Decoction from the aspects of protection of gastrointestinal mucosa,anti-inflammatory and bactericidal effects,immune regulation,regulation of neurotransmitters,anti-tumor effects,blood glucose lowering,and improvement of insulin resistance,providing reference for the in-depth research and application of Banxia Xiexin Decoction.

Objective To investigate the differences and influencing factors of chronic heart failure(CHF)with qi deficiency and blood stasis syndrome and with other TCM syndrome types.Methods Totally 354 CHF patients from Dongzhimen Hospital of Beijing University of Chinese Medicine were enrolled from January 2019 to December 2023,including 242 cases of qi deficiency and blood stasis syndrome,52 cases of qi and yin deficiency and blood stasis syndrome,and 60 cases of yang qi deficiency and blood stasis syndrome.The general demographic sociological characteristics of patients with each syndrome type,the New York Heart Association cardiac function classification(NYHA classification),and the heart failure classification were collected.The cardiac function-related indexes and laboratory examination indicators were detected.The Minnesota Heart Failure Patients'Life Questionnaire(MLHFQ)was used to evaluate the quality of life of the patients in three areas:physical,emotional and other three domains.The differences of the above factors among patients with different syndrome types were compared,and a disordered multi-categorical logistics regression model of TCM syndrome types was constructed to analyze the association between the above factors and qi deficiency and blood stasis syndrome.Traditional Chinese Medicine Inheritance Calculation Platform 3.0 was used to analyze the frequency,property,taste and meridian tropism of prescription drugs.Results The proportion of patients with NYHAⅡ qi deficiency and blood stasis syndrome was higher than that of the group with qi and yin deficiency and blood stasis syndrome(P<0.05);the left ventricular ejection fraction in patients with yang qi deficiency and blood stasis pattern was significantly lower than that in patients with qi deficiency and blood stasis pattern(P<0.05);and the scores of the body domain,other domain and the total score of the MLHFQ questionnaire in patients with qi deficiency and blood stasis pattern were lower than those of the other two syndrome types(P<0.05);the serum neutrophils(NE%),C-reactive protein(CRP)and interleukin-6(IL-6)in the qi and yin deficiency and blood stasis syndrome were higher than those in the group with qi deficiency and blood stasis syndrome(P<0.05).Multivariate Logistics regression analysis showed that arrhythmia,CRP and IL-6 were independent influencing factors for CHF with qi deficiency and blood stasis syndrome(P<0.05).Totally 284 prescriptions were included,involving 190 kinds of Chinese materia medica.The top 10 were Astragali Radix,Ophiopogonis Radix,Lonicerae Japonicae Flos,Pseudostellariae Radix,Hordei Fructus Germinatus,Galli Gigerii Endothelium Corneumm,Puerariae Lobatue Radix,Scrophulariae Radix,Ziziphi Spinosae Semen and Citri Reticulatae Pericarpium.Conclusion Qi deficiency and blood stasis syndrome is a relatively stable stage of CHF,with cardiac function mainly distributed in grade Ⅱ,Ⅲ,with a relatively high proportion of heart failure with preserved ejection fraction,fewer other underlying diseases,lower inflammatory indicators,and relatively good quality of life.Combined arrhythmia,CRP and IL-6 indicators can be used as an auxiliary basis for syndrome differentiation of qi deficiency and blood stasis syndrome.

AIM To investigate the effects of Modified Baitouweng Decoction and Lizhong Decoction on mouse ulcerative colitis(UC).METHODS The mouse model of UC was established by 3％dextran sulfate sodium(DSS)induction.The C57BL/6 mice were randomly divided into the blank group,the model group,the low,medium and high dose Modified Baitouweng Decoction and Lizhong Decoction groups(3,6,12 g/kg),and sulfasalazine group(300 mg/kg),for 7 days gavage of the appropriate drugs,with 10 mice in each group.The mice had their disease activity index(DAI)and colonic mucosal damage index(CMDI)calculated;their colonic length and unit colonic weight measured;their histopathologic changes of colon observed by HE;their colonic ROS,MDA levels and GSH-Px,SOD activities detected by superoxide anion fluorescent probes and kits;their colonic levels of TNF-α,IL-6 and IL-1β detected by ELISA;their colonic LC3 expression detected by immunofluorescence method;and their colonic AMPK,mTOR and p70S6K protein expressions detected by Western blot method.RESULTS Compared with the blank group,the model group displayed significantly higher DAI score,CMDI score,unit colon weight,pathology score,ROS and MDA content,TNF-α,IL-6,and IL-1β levels,and mTOR and p70S6K protein expression(P＜0.01);and significantly lower colon length,GSH-Px and SOD activity,LC3 level,and phosphorylated AMPK protein expression(P＜0.01).Compared with the model group,the groups intervened with Modified Baitouweng Decoction and Lizhong Decoction or sulfasalazine shared decreased DAI score,CMDI score,unit colon mass,pathology score,ROS,MDA,TNF-α,IL-6,IL-1β levels,mTOR,p70S6K protein expressions(P＜0.01);and significantly improved symptomsin terms of the elevated colonic length,GSH-Px,SOD activities,LC3 level,AMPK protein expression(P＜0.01).CONCLUSION Modified Baitouweng Decoction and Lizhong Decoction may attenuate inflammatory response and oxidative damage in UC mouse models via AMPK/mTOR/p70S6K signaling pathway.

Atherosclerosis is a chronic vascular disease caused by lipid deposition in the inner wall of blood vessels.Ferroptosis is a non-apoptotic form of cell death characterized by iron dependence and lipid reactive oxygen accumulation.Recent studies have shown that ferroptosis is closely related to the occurrence and development of atherosclerosis.This article explained the correlation between ferroptosis and atherosclerosis from the aspects of foam cell formation,endothelial cell death,vascular smooth muscle proliferation and calcification,and believed that ferroptosis runs through its pathological process.By combing the current research status of the mechanism of Chinese materia medica regulating ferroptosis to treat atherosclerosis,it can be seen that TCM monomers and compounds can reduce endothelial cell dysfunction and inflammatory response,slow down oxidative stress levels,and reduce the accumulation of oxidized lipids under the intima of arterial blood vessels by regulating ferroptosis p53,Nrf2 signaling pathway,amino acid metabolism,lipid metabolism,etc.,so that the blood vessels reach homeostasis,which can provide a reference for the exploration of clinical treatment strategies for atherosclerosis.

The glymphatic system is a recently discovered essential waste-clearance pathway in the central nervous system that plays a pivotal role in maintaining brain homeostasis.Growing evidence suggests that dysfunction of this system is closely associated with the pathogenesis of various neurodegenerative disorders;however,its precise mechanistic involvement in Parkinson's disease is poorly understood.This review systematically summarizes the structural and functional characteristics of the glymphatic system,provides an in-depth exploration of its potential role in Parkinson's disease pathophysiology,and synthesizes current research evidence on glymphatic system-targeted therapeutic strategies,with the aim of establishing a theoretical foundation for advancing the understanding of PD pathogenesis and developing novel diagnostic and therapeutic approaches.

The protein kinase A/protein kinase G/protein kinase C-family (AGC kinase family) of eukaryotes is involved in regulating numerous biological processes. The 3-phosphoinositide- dependent protein kinase 1 (PDK1), is a conserved serine/threonine kinase in eukaryotes. To understand the roles of PDK1 homologous genes in cell death and immunity in tetraploid Nicotiana tabacum, the previuosly generated transgenic CRISPR/Cas9 lines, in which 5-7 alleles of the 4 homologous PDK1 genes (NtPDK1a/1b/1c/1d homologs) simultaneously knocked out, were used in this study. Our results showed that the hypersensitive response (HR) triggered by transient overexpression of active Pto (Pto^Y207D) or soybean GmMEKK1 was significantly delayed, whereas the resistance to Pseudomonas syrangae pv. tomato DC3000 (Pst DC3000) and tobacco mosaic virus (TMV) was significantly elevated in these partial knockout lines. The elevated resistance to Pst DC3000 and TMV was correlated with the elevated activation of NtMPK6, NtMPK3, and NtMPK4. Taken together, our results indicated that NtPDK1s play a positive role in cell death but a positive role in disease resistance, likely through negative regulation of the MAPK signaling cascade.
Nicotiana/virology* ; Disease Resistance/genetics* ; Plant Diseases/immunology* ; Plants, Genetically Modified/genetics* ; Gene Knockout Techniques ; Plant Proteins/genetics* ; CRISPR-Cas Systems ; Protein Serine-Threonine Kinases/genetics* ; 3-Phosphoinositide-Dependent Protein Kinases/genetics* ; Pyruvate Dehydrogenase Acetyl-Transferring Kinase ; Tobacco Mosaic Virus/pathogenicity*

Objective:To explore the incidence status,influencing factors and short-term prognosis characteristics of early onset coronary heart disease in women in Wansheng District of Chongqing,and to provide scientific basis for formulating regional prevention and treatment strategies.Methods:This study was a single-center retrospective study,100 coronary heart disease in women from January 2022 to December 2023 at Chongqing Wansheng Economic and Technological Development Zone People's Hospital were prospective selected,and they were divided into early onset group of 40 cases(≤ 65 years old)and late onset group of 60 cases(＞65 years old)based on their age of onset.Another 60 healthy women who underwent physical examinations during the same period to exclude coronary heart disease were selected as the control group.Univariate factor and multiple factor logistic regression analysis were used to identify independent risk factors for early onset coronary heart disease in women.Draw receiver operating characteristic(ROC)curve for the subjects,the efficacy of risk factors in predicting early onset coronary heart disease based on the area under the curve(AUC)of ROC curve were evaluated.Patients were followed up for 1 year to observe the occurrence of major adverse cardiovascular events(MACE).Result:Among 100 fcoronary heart disease in women,the early onset group accounted for 40.00％(40/100).Univariate analysis showed that age,hyperlipidemia history,smoking history,hypertension history,family history,diabetes history,total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C)were related to the early onset coronary heart disease.Multivariate analysis showed that,hyperlipidemia history(OR=4.124,95％CI:2.343-7.217),smoking history(OR=3.564),hypertension(OR=3.253),family history(OR=2.981),diabetes history(OR=2.873)were independent risk factors.ROC curve analysis results showed that joint evaluation had the best predictive value,with AUC of 0.829,which was higher than the AUC of individual evaluation for each factor.The incidence of MACE in the early onset group(45.00％)was significantly higher than that in the late onset group(P＜0.05).Conclusion:Early onset coronary heart disease in women in Wansheng District of Chongqing is related to the hyperlipidemia history,smoking,hypertension history,family history and diabetes history.The incidence of MACE in early-onset patients followed up for 1 year is higher than that in late-onset patients.

The glymphatic system is a recently discovered essential waste-clearance pathway in the central nervous system that plays a pivotal role in maintaining brain homeostasis.Growing evidence suggests that dysfunction of this system is closely associated with the pathogenesis of various neurodegenerative disorders;however,its precise mechanistic involvement in Parkinson's disease is poorly understood.This review systematically summarizes the structural and functional characteristics of the glymphatic system,provides an in-depth exploration of its potential role in Parkinson's disease pathophysiology,and synthesizes current research evidence on glymphatic system-targeted therapeutic strategies,with the aim of establishing a theoretical foundation for advancing the understanding of PD pathogenesis and developing novel diagnostic and therapeutic approaches.