Aim To explore the effect of the classical famous prescription Dahuang Zhechong pill(DHZCP)on relieving liver cirrhosis by regulating the stress fiber remodeling mediated by mechanistic signaling pathway and to explore the underlying mechanism.Methods Mice were randomly divided into the control group,model group,DHZCP low-dose group,DHZCP high-dose group,and Colchicine-positive control group.The liver cirrhosis mouse model was constructed by intrap-eritoneal injection of olive oil-solubilized CCl4.HE staining and serologic markers were used to reflect liver injury.Masson staining was used to evaluate collagen deposition in liver tissue.ELISA was applied to detect vasoactive molecules and cancer indicators.Atomic force microscopy was employed to detect liver tissue stiffness.Color Doppler diagnostic instrument was used to assess portal blood flow velocity.Western blot was utilized to detect ROCK2 expression and phosphoryla-tion of YAP,Cofilin,and MLC.Results The liver tis-sues in the model group had obvious inflammatory cell infiltration and collagen deposition,accompanied by significant elevation of serum transaminases and fibrosis indexes.Similarly,vasoactive molecules and cancer in-dicators were elevated,and the mechanoregulatory pro-tein ROCK2 expression and phosphorylation of Cofilin and MLC were elevated,with YAP being strongly de-phosphorylated.Both low and high doses of DHZCP re-versed the pathological changes,serological indices,and inhibited the activation of the stress fiber(SF)re-modeling mechanistic signaling pathway.Conclusion DHZCP effectively ameliorates liver tissue lesions in mice with liver cirrhosis,and its mechanism may be re-lated to the inhibition of SF remodeling mechanistic signaling pathway.

Osteosarcoma (OS) is the most prevalent primary malignant bone tumor affecting children and adolescents. Despite ongoing research efforts, the 5-year survival rate has remained stagnant for many years, highlighting the critical need for novel drug development to enhance current treatment protocols. Ziyuglycoside II (ZYG II), a triterpenoid saponin extracted from S. officinalis, has recently demonstrated antitumor properties. This study evaluates the antitumor effect of ZYG II on osteosarcoma and elucidates its mechanism of action through the co-regulation of p53 and estrogen-related receptor gamma (ESRRG), which inhibits disease progression. The research employs in vitro experiments using multiple established osteosarcoma cell lines, as well as in vivo studies utilizing a nude mouse model of orthotopic xenograft osteosarcoma. Additionally, ESRRG shRNA was used to construct stable ESRRG-reducing OS cell lines to investigate the molecular mechanism by which ZYG II exerts its anti-osteosarcoma effects through the co-regulation of ESRRG and p53. Results indicate that ZYG II administration led to decreased OS cell viability and reduced tumor volumes. Furthermore, cell cycles were arrested at the G₀/G₁ phase, while the proportion of apoptotic cells increased. Expression of p53, ESRRG, p21, Bax, Cleaved Caspase-9, and Cleaved Caspase-3 proteins increased, while expression of CDK4, Cyclin D1, and Bcl-2 proteins decreased. Multiple ZYG II and ESRRG docking patterns were simulated through molecular docking. Comparing the pharmacodynamic response of ZYG II to OS cell lines with reduced ESRRG and normal expression demonstrated that ZYG II inhibits osteosarcoma progression, induces cell cycle arrest, and promotes cell apoptosis through the coordination of p53 and ESRRG. In conclusion, ZYG II inhibits osteosarcoma progression, leads to cell cycle arrest, and promotes cell apoptosis through synergistic regulation of p53 and ESRRG.
Osteosarcoma/physiopathology* ; Tumor Suppressor Protein p53/genetics* ; Humans ; Animals ; Saponins/chemistry* ; Bone Neoplasms/physiopathology* ; Signal Transduction/drug effects* ; Cell Line, Tumor ; Mice, Nude ; Mice ; Apoptosis/drug effects* ; Receptors, Estrogen/genetics* ; Mice, Inbred BALB C ; Female ; Male ; Xenograft Model Antitumor Assays

The development of bone in human body and the maintenance of bone mass in adulthood are regulated by a variety of biological factors. Myocyte enhancer factor 2C (MEF2C), as one of the many factors regulating bone tissue development and balance, has been shown to play a key role in bone development and metabolism. However, there is limited systematic analysis on the effects of MEF2C on bone tissue. This article reviews the role of MEF2C in bone development and metabolism. During bone development, MEF2C promotes the development of neural crest cells (NC) into craniofacial cartilage and directly promotes cartilage hypertrophy. In terms of bone metabolism, MEF2C exhibits a differentiated regulatory model across different types of osteocytes, demonstrating both promoting and other potential regulatory effects on bone formation, with its stimulating effect on osteoclasts being determined. In view of the complex roles of MEF2C in bone tissue, this paper also discusses its effects on some bone diseases, providing valuable insights for the physiological study of bone tissue and strategies for the prevention of bone diseases.
Humans ; MEF2 Transcription Factors/physiology* ; Bone and Bones/metabolism* ; Animals ; Bone Development/physiology* ; Osteogenesis/physiology* ; Myogenic Regulatory Factors/physiology*

Inflammatory diseases (IDs) are a general term of diseases characterized by chronic inflammation as the primary pathogenetic mechanism, which seriously affect the quality of patient′s life and cause significant social and medical burden. Current drugs for IDs include nonsteroidal anti-inflammatory drugs, corticosteroids, immunomodulators, biologics, and antioxidants, but these drugs may cause gastrointestinal side effects, induce or worsen infections, and cause non-response or intolerance. Given the outstanding performance of metal polyphenol network (MPN) in the fields of drug delivery, biomedical imaging, and catalytic therapy, its application in the diagnosis and treatment of IDs has attracted much attention and significant progress has been made. In this paper, we first provide an overview of the types of IDs and their generating mechanisms, then sort out and summarize the different forms of MPN in recent years, and finally discuss in detail the characteristics of MPN and their latest research progress in the diagnosis and treatment of IDs. This research may provide useful references for scientific research and clinical practice in the related fields.

With the rapid development of social economy and the continuous improvement of human living standard, the incidence, fatality and recurrence rates of cardiovascular disease (CVD) are increasing year by year, which seriously affects people's life and health. Conventional therapeutic drugs have limited improvement on the disability rate, so the search for new therapeutic drugs and action targets has become one of the hotspots of current research. In recent years, the therapeutic role of the natural compound rosmarinic acid (RA) in CVD has attracted much attention, which is capable of preventing CVD by modulating multiple signalling pathways and exerting physiological activities such as antioxidant, anti-apoptotic, anti-inflammatory, anti-platelet aggregation, as well as anti-coagulation and endothelial function protection. In this paper, the role of RA in the prevention of CVD is systematically sorted out, and its mechanism of action is summarised and analysed, with a view to providing a scientific basis and important support for the in-depth exploration of the prevention value of RA in CVD and its further development as a prevention drug.

Objectives:Coronary slow flow(CSF)has long been regarded as a marker of coronary microvascular dysfunction(CMD).This study aims to evaluate the diagnostic value of CSF for CMD in patients with angina and nonobstructive coronary arteries(ANOCA).Methods:The study data were derived from the ANOCA-CMD prospective cohort study.All enrolled patients underwent coronary angiography and concurrent coronary physiological assessments in the left anterior descending artery using pressure-wire and thermodilution techniques to obtain coronary flow reserve(CFR)and the index of microcirculatory resistance(IMR).Based on the results,CMD was classified into four subtypes:CMD with elevated IMR(IMR≥25),CMD with reduced CFR(CFR<2.5),CMD with either reduced CFR or elevated IMR(CFR<2.5 or IMR≥25),and CMD with both reduced CFR and elevated IMR(CFR<2.5 and IMR≥25).The corrected thrombolysis in myocardial infarction(TIMI)frame count(CTFC)in the left anterior descending artery was calculated from coronary angiography images,with CSF defined as CTFC>27.This study evaluated the correlation between CTFC,CFR,and IMR,and investigated the diagnostic value of CSF for CMD in ANOCA patients.Results:A total of 103 ANOCA patients were enrolled in this study,with a mean age of(64.2±10.6)years,and 53.4％were female.Among them,57 patients(55.3％)were diagnosed with coronary slow flow.Patients with slow flow had higher IMR(P<0.001)and CFR(P=0.041).Similarly,the proportion of CMD with elevated IMR was higher in the slow flow group(P<0.001),while the proportion of CMD with reduced CFR was lower(P=0.044).There was no significant difference between the groups in the proportions of CMD with either reduced CFR or elevated IMR or CMD with both reduced CFR and elevated IMR(all P>0.05).CTFC was positively correlated with hyperemic mean transit time(r=0.424,P<0.001),IMR(r=0.430,P<0.001),and CFR(r=0.211,P=0.032).The area under the curve(AUC)of CTFC for diagnosing CMD with elevated IMR was 0.721(95％CI:0.623-0.819)with an accuracy of 67％(57％,76％),for diagnosing CMD with reduced CFR was 0.610(95％CI:0.499-0.720)with an accuracy of 60％(50％,70％),for diagnosing CMD with either reduced CFR or elevated IMR was 0.549(95％CI:0.425-0.673)with an accuracy of 47％(37％,57％),and for diagnosing CMD with both reduced CFR and elevated IMR was 0.582(95％CI:0.471-0.693)with an accuracy of 47％(37％,57％).Thus,CSF demonstrated limited diagnostic values across all subtypes of CMD.Conclusions:In ANOCA patients,CSF cannot serve as an effective diagnostic marker for CMD.Therefore,in clinical practice,the slow flow phenomenon should not be directly equated with the presence of coronary microvascular dysfunction in ANOCA patients.

Aim To explore the effect of the classical famous prescription Dahuang Zhechong pill(DHZCP)on relieving liver cirrhosis by regulating the stress fiber remodeling mediated by mechanistic signaling pathway and to explore the underlying mechanism.Methods Mice were randomly divided into the control group,model group,DHZCP low-dose group,DHZCP high-dose group,and Colchicine-positive control group.The liver cirrhosis mouse model was constructed by intrap-eritoneal injection of olive oil-solubilized CCl4.HE staining and serologic markers were used to reflect liver injury.Masson staining was used to evaluate collagen deposition in liver tissue.ELISA was applied to detect vasoactive molecules and cancer indicators.Atomic force microscopy was employed to detect liver tissue stiffness.Color Doppler diagnostic instrument was used to assess portal blood flow velocity.Western blot was utilized to detect ROCK2 expression and phosphoryla-tion of YAP,Cofilin,and MLC.Results The liver tis-sues in the model group had obvious inflammatory cell infiltration and collagen deposition,accompanied by significant elevation of serum transaminases and fibrosis indexes.Similarly,vasoactive molecules and cancer in-dicators were elevated,and the mechanoregulatory pro-tein ROCK2 expression and phosphorylation of Cofilin and MLC were elevated,with YAP being strongly de-phosphorylated.Both low and high doses of DHZCP re-versed the pathological changes,serological indices,and inhibited the activation of the stress fiber(SF)re-modeling mechanistic signaling pathway.Conclusion DHZCP effectively ameliorates liver tissue lesions in mice with liver cirrhosis,and its mechanism may be re-lated to the inhibition of SF remodeling mechanistic signaling pathway.

Objectives:Coronary slow flow(CSF)has long been regarded as a marker of coronary microvascular dysfunction(CMD).This study aims to evaluate the diagnostic value of CSF for CMD in patients with angina and nonobstructive coronary arteries(ANOCA).Methods:The study data were derived from the ANOCA-CMD prospective cohort study.All enrolled patients underwent coronary angiography and concurrent coronary physiological assessments in the left anterior descending artery using pressure-wire and thermodilution techniques to obtain coronary flow reserve(CFR)and the index of microcirculatory resistance(IMR).Based on the results,CMD was classified into four subtypes:CMD with elevated IMR(IMR≥25),CMD with reduced CFR(CFR<2.5),CMD with either reduced CFR or elevated IMR(CFR<2.5 or IMR≥25),and CMD with both reduced CFR and elevated IMR(CFR<2.5 and IMR≥25).The corrected thrombolysis in myocardial infarction(TIMI)frame count(CTFC)in the left anterior descending artery was calculated from coronary angiography images,with CSF defined as CTFC>27.This study evaluated the correlation between CTFC,CFR,and IMR,and investigated the diagnostic value of CSF for CMD in ANOCA patients.Results:A total of 103 ANOCA patients were enrolled in this study,with a mean age of(64.2±10.6)years,and 53.4％were female.Among them,57 patients(55.3％)were diagnosed with coronary slow flow.Patients with slow flow had higher IMR(P<0.001)and CFR(P=0.041).Similarly,the proportion of CMD with elevated IMR was higher in the slow flow group(P<0.001),while the proportion of CMD with reduced CFR was lower(P=0.044).There was no significant difference between the groups in the proportions of CMD with either reduced CFR or elevated IMR or CMD with both reduced CFR and elevated IMR(all P>0.05).CTFC was positively correlated with hyperemic mean transit time(r=0.424,P<0.001),IMR(r=0.430,P<0.001),and CFR(r=0.211,P=0.032).The area under the curve(AUC)of CTFC for diagnosing CMD with elevated IMR was 0.721(95％CI:0.623-0.819)with an accuracy of 67％(57％,76％),for diagnosing CMD with reduced CFR was 0.610(95％CI:0.499-0.720)with an accuracy of 60％(50％,70％),for diagnosing CMD with either reduced CFR or elevated IMR was 0.549(95％CI:0.425-0.673)with an accuracy of 47％(37％,57％),and for diagnosing CMD with both reduced CFR and elevated IMR was 0.582(95％CI:0.471-0.693)with an accuracy of 47％(37％,57％).Thus,CSF demonstrated limited diagnostic values across all subtypes of CMD.Conclusions:In ANOCA patients,CSF cannot serve as an effective diagnostic marker for CMD.Therefore,in clinical practice,the slow flow phenomenon should not be directly equated with the presence of coronary microvascular dysfunction in ANOCA patients.

Platycodonis Radix is the dry root of Platycodon grandiflorum of Campanulaceae, which has a variety of pharmacological effects and is a commonly used bulk Chinese medicine. In this study, the chloroplast genome sequences of six P. grandiflorum from different producing areas has been sequenced with Illumina HiSeq X Ten platform. The specific DNA barcodes were screened, and the germplasm resources and genetic diversity were analyzed according to the specific barcodes. The total length of the chloroplast genome of 6 P. grandiflorum samples was 172 260-172 275 bp, and all chloroplast genomes showed a typical circular tetrad structure and encoded 141 genes. The comparative genomics analysis and results of amplification efficiency demonstrated that trnG-UCC and ndhG_ndhF were the potential specific DNA barcodes for identification the germplasm resources of P. grandiflorum. A total of 305 P. grandiflorum samples were collected from 15 production areas in 9 provinces, for which the fragments of trnG-UCC and ndhG_ndhF were amplificated and the sequences were analyzed. The results showed that trnG-UCC and ndhG_ndhF have 5 and 11 mutation sites, respectively, and 5 and 7 haplotypes were identified, respectively. The combined analysis of the two sequences formed 13 haplotypes (named Hap1-Hap13), and Hap4 is the main genotype, followed by Hap1. The unique haplotypes possessed by the three producing areas can be used as DNA molecular tags in this area to distinguish from the germplasm resources of P. grandiflorum from other areas. The haplotype diversity, nucleotide diversity and genetic distance were 0.94, 4.79×10^-3 and 0.000 0-0.020 3, respectively, suggesting that the genetic diversity was abundant and intraspecific kinship was relatively close. This study laid a foundation for the identification of P. grandiflorum, the protection and utilization of germplasm resources, and molecular breeding.