Objective To explore the mechanism of Modified Xiaoxianxiong Decoction(MXD)in"treating different diseases with the same method"for type 2 diabetes mellitus(T2DM)and obstructive sleep apnea(OSA)using network pharmacology and molecular docking.Methods Active components and related targets of the seven herbs in MXD(composed of Coptidis Rhizoma,Pinelliae Rhizoma,Trichosanthis Fructus,Bupleuri Radix,Salviae Miltiorrhizae Radix et Rhizoma,Paeoniae Radix Rubra,Astragali Radix)were retrieved and screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).Swiss Target Prediction was used for target prediction of active components,followed by gene standardization using the UniProt database.Disease-related targets of T2DM and OSA were obtained from DisGeNET,OMIM,and GeneCards databases.A Venn diagram was used to identify overlapping targets between disease-related targets and active component-related targets,yielding potential therapeutic targets of MXD for both T2DM and OSA.The STRING database and Cytoscape 3.10.2 were employed to construct a protein-protein interaction(PPI)network and a"drug-component-target"network,respectively.Core active components and core targets were identified through network topology analysis.GO functional and KEGG pathway enrichment analyses were performed on potential targets using Metascape.Molecular docking validation was conducted using AutoDock to assess binding affinity between core targets and compounds.Results A total of 157 active components of MXD acted on 1 043 protein targets.After comparison with 1 798 OSA-related targets and 3 466 T2DM-related targets,253 potential therapeutic targets were identified.GO enrichment analysis revealed that these targets were primarily involved in biological processes such as upregulation of phosphorus metabolism,regulation of cell migration,circulatory system processes,and hormone level regulation.KEGG pathway analysis identified key pathways including Rap1,AGE-RAGE,cAMP,and Alzheimer's disease.PPI and"drug-component-target"network topology analysis screened 39 core targets(e.g.,IL-6,TNF,Akt1,IL-1β,EGFR)and core active components(e.g.,salvianolic acid B,tanshinone IIA,baicalin,curcumin).Molecular docking confirmed stable binding between these components and their corresponding target proteins.Conclusion The common pharmacodynamic basis of MXD in"treating different diseases with the same method"for T2DM and OSA includes active components such as salvianolic acid B,baicalin,and curcumin.The shared mechanism may involve key targets(e.g.,IL-6,TNF,Akt1)and modulation of signaling pathways such as Rap1,AGE-RAGE,and cAMP.

This study investigates the therapeutic effect and underlying mechanism of Compound Ziyin Granules(CZYG) on postmenopausal osteoporosis(PMOP) induced by bilateral ovariectomy in rats. Six-month-old female SD rats were randomly divided into sham-operated(sham) group, ovariectomy(OVX) model group, high-, medium-, and low-dose CZYG groups, and alendronate sodium(AS) group. After 30 days of model establishment, treatment was administered by gavage once daily for 8 weeks, followed by sample collection. Enzyme-linked immunosorbent assay(ELISA) was used to measure serum levels of calcium ions, alkaline phosphatase(AKP), estrogen(E_2), osteoprotegerin(OPG), osteocalcin(BGP), tartrate-resistant acid phosphatase(TRAP), and type Ⅰ procollagen N-terminal propeptide(PINP). Hematoxylin-eosin(HE) staining was used to observe the histopathological changes in the femurs of rats, while micro-computed tomography(micro-CT) was used to analyze the microstructure of the distal femur. Western blot analysis was performed to measure the expression levels of bone metabolism-related proteins, including wingless-type MMTV integration site family member 2(Wnt2), β-catenin, low-density lipoprotein receptor-related protein 5(LRP5), glycogen synthase kinase-3β(GSK-3β). The mRNA expression levels of Wnt2, β-catenin, LRP5, GSK-3β, p-GSK-3β were determined by quantitative real-time PCR(qRT-PCR). Thirty days after bilateral ovariectomy, compared to the sham group, the OVX group showed significant increases in body weight and significant decreases in uterine coefficient. After 8 weeks of treatment, compared to the OVX group, CZYG(medium and high doses) and AS reduced body weight, with high-dose CZYG and AS significantly increasing the uterine coefficient. Serum levels of AKP and TRAP were significantly elevated, while levels of calcium, E_2, BGP, and OPG were significantly decreased in the OVX group. Compared to the OVX group, CZYG and AS significantly reduced serum levels of AKP and TRAP, while high-dose CZYG and AS notably increased the levels of E_2, BGP, OPG, and PINP. Micro-CT and HE staining results indicated that CZYG(medium and high doses) and AS significantly increased bone tissue volume, trabecular number, bone mineral density, and improved the microstructure of the femur. Compared to the OVX group, high-dose CZYG and AS significantly upregulated the protein and mRNA expression levels of Wnt2, β-catenin, and LRP5, and downregulated the phosphorylation level of p-GSK-3β. These results suggest that CZYG can improve PMOP by promoting estrogen secretion, improving bone metabolism indicators, increasing trabecular number and bone mineral density. Its mechanism may be related to the regulation of the Wnt/β-catenin signaling pathway.
Animals ; Female ; Rats, Sprague-Dawley ; Osteoporosis, Postmenopausal/genetics* ; Rats ; Wnt Signaling Pathway/drug effects* ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; beta Catenin/genetics* ; Osteoprotegerin/metabolism* ; Ovariectomy ; Calcium/blood* ; Bone Density/drug effects*

The evaluation of blood compatibility of biomaterials is crucial for ensuring the clinical safety of implantable medical devices. To address the limitations of traditional testing methods in real-time monitoring and electrical property analysis, this study developed a portable electrical impedance tomography (EIT) system. The system uses a 16-electrode design, operates within a frequency range of 1 to 500 kHz, achieves a signal to noise ratio (SNR) of 69.54 dB at 50 kHz, and has a data collection speed of 20 frames per second. Experimental results show that the EIT system developed in this study is highly consistent with a microplate reader ( R ²=0.97) in detecting the hemolytic behavior of industrial-grade titanium (TA3) and titanium alloy-titanium 6 aluminum 4 vanadium (TC4) in anticoagulated bovine blood. Additionally, with the support of a multimodal image fusion Gauss-Newton one-step iterative algorithm, the system can accurately locate and monitor in real-time the dynamic changes in blood permeation and coagulation caused by TC4 in vivo. In conclusion, the EIT system developed in this study provides a new and effective method for evaluating the blood compatibility of biomaterials.
Electric Impedance ; Animals ; Tomography/instrumentation* ; Biocompatible Materials ; Materials Testing/instrumentation* ; Cattle ; Titanium ; Alloys ; Prostheses and Implants

With the increase in the obese population and the aging of the society,the incidence rates of type 2 diabetes mellitus(T2DM)and obstructive sleep apnea(OSA)continue to increase,and more than half of the patients with T2DM also suffer from OSA.T2DM patients with OSA have a higher risk of developing macrovascular and microvascular complications,which severely impairs their quality of life,and early identification of T2DM patients with OSA can improve their prognosis.This article summarizes the latest re-search advances in the pathogenesis,biomarkers,and treatment measures of T2DM with OSA,in order to provide insights for the screening,diagnosis,and treatment of T2DM with OSA.

Huntington's disease (HD) is an inherited neurodegenerative disorder caused by the abnormal expansion of CAG trinucleotide repeats in the Huntingtin gene (HTT) located on chromosome 4. It is transmitted in an autosomal dominant manner and is characterized by motor dysfunction, cognitive decline, and emotional disturbances. To date, there are no curative treatments for HD have been developed; current therapeutic approaches focus on symptom relief and comprehensive care through coordinated pharmacological and nonpharmacological methods to manage the diverse phenotypes of the disease. International clinical guidelines for the treatment of HD are continually being revised in an effort to enhance care within a multidisciplinary framework. Additionally, innovative gene and cell therapy strategies are being actively researched and developed to address the complexities of the disorder and improve treatment outcomes. This review endeavours to elucidate the current and emerging gene and cell therapy strategies for HD, offering a detailed insight into the complexities of the disorder and looking forward to future treatment paradigms. Considering the complexity of the underlying mechanisms driving HD, a synergistic treatment strategy that integrates various factors-such as distinct cell types, epigenetic patterns, genetic components, and methods to improve the cerebral microenvironment-may significantly enhance therapeutic outcomes. In the future, we eagerly anticipate ongoing innovations in interdisciplinary research that will bring profound advancements and refinements in the treatment of HD.
Huntington Disease/pathology* ; Humans ; Genetic Therapy/methods* ; Animals ; Huntingtin Protein/genetics* ; Cell- and Tissue-Based Therapy/methods*

OBJECTIVE: This study aimed to reexplore minimum iodine excretion and to build a dietary iodine recommendation for Chinese adults using the obligatory iodine loss hypothesis. METHODS: Data from 171 Chinese adults (19-21 years old) were collected and analyzed based on three balance studies in Shenzhen, Yinchuan, and Changzhi. The single exponential equation was accordingly used to simulate the trajectory of 24 h urinary iodine excretion as the low iodine experimental diets offered (iodine intake: 11-26 μg/day) and to further deduce the dietary reference intakes (DRIs) for iodine, including estimated average requirement (EAR) and recommended nutrient intake (RNI). RESULTS: The minimum iodine excretion was estimated as 57, 58, and 51 μg/day in three balance studies, respectively. Moreover, it was further suggested as 57, 58, and 51 μg/day for iodine EAR, and 80, 81, and 71 μg/day for iodine RNI or expressed as 1.42, 1.41, and 1.20 μg/(day·kg) of body weight. CONCLUSION The iodine DRIs for Chinese adults were established based on the obligatory iodine loss hypothesis, which provides scientific support for the amendment of nutrient requirements.
Humans ; Iodine/administration & dosage* ; Male ; Female ; China ; Young Adult ; Diet ; Adult ; Nutritional Requirements ; East Asian People

Objective:To discuss the effect of Yes-associated protein(YAP)silencing on the proliferation,migration,and invasion capabilities of the human cervical cancer(CC)SiHa cells.Methods:The human CC SiHa cells were cultured in vitro,and the lentiviral YAP shRNA was transfected into the SiHa cells to establish stably transfected YAP-shRNA experimental group(sh-YAP group)and empty plasmid control group(control group).Western blotting method was used to detect the silencing effect of YAP;immunofluorescence method was used to detect the microfilament number and morphology of actin filaments(F-actin)in the cells in both groups;CCK-8 method was used to detect the survival rates of the cells in two groups;Transwell chamber assay and wound healing assay were used to detect the numbers of migration and invasion cells and scratch healing rates of the cells in two groups;Western blotting method was used to detect the expression levels of epithelial-mesenchymal transition(EMT)markers(E-cadherin and Snail),DNA damage repair-related proteins(γ-H2AX),and apoptosis-related proteins[c-MYC and B-cell lymphoma-2(Bcl-2)]in the cells in two groups.Results:The results of lentiviral YAP shRNA transfection into SiHa cells showed that the expression level of YAP protein in the SiHa cells was significantly decreased(P＜0.05).The immunofluorescence results showed that after YAP silencing,the F-actin in SiHa cells was sparse and regularly arranged,with a reduced number of cells and a shriveled appearance.The CCK-8 results showed that compared with control group,the survival rate of the SiHa cells in sh-YAP group was significantly decreased cultured for 24 and 48 h(P＜0.01).The results of Transwell chamber assay and the wound healing assay showed that compared with control group,the numbers of migration and invasion SiHa cells in sh-YAP group were significantly decreased(P＜0.01),and the cell scratch healing rates were signifiantly decreased(P＜0.05).The Western blotting results showed that compared with control group,the expression level of E-cadherin protein in the cells in sh-YAP group was increased(P＜0.05),and the expression levels of c-MYC,Bcl-2,and γ-H2AX proteins were decreased(P＜0.05 or P＜0.01).Conclusion:YAP gene silencing leads to the depolymerization of F-actin in the human CC SiHa cells and regulates the apoptosis and DNA damage repair,potentially reversing the EMT process,thereby inhibiting the proliferation and migration of the tumor cells.

Objective:To discuss the regulatory role of complement alternative pathway in mouse colorectal cancer(CRC)liver metastasis model based on bioinformatics methods,and to clarify its mechanism through experimental verification.Methods:Using"CRC liver metastasis"as the keyword,the GSE81558 dataset was retrieved from Gene Expression Omnibus(GEO)database,including normal colon tissue samples,CRC tissue samples and CRC liver metastasis tissue samples.Bioinformatics methods were used to analyze and screen differentially expressed genes(DEGs).Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed using R and Cytoscape software,and the results were visualized.Search Tool for the Retrieval of Interacting Genes/Proteins(STRING)database was used to evaluate protein-protein interactions(PPIs)of DEGs and construct PPI network.Twelve C57BL/6 mice were injected with SL4 tumor cells into spleen,and the liver tissues were collected at 0,7 and 14 d.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of complement pathway-related genes in liver metastatic foci.The CRC liver metastasis mouse model was used to verify the complement signaling pathway.The mice were divided into control group,factor B knockout group(FB-/-)and C4 factor knockout group(C4-/-),and there were 6 mice in each group.The liver weights of the mice were measured;HE staining was used to detect the percentage of metastatic area in liver tissue in control group and FB-/-group;immunohistochemistry was used to detect macrophage infiltration in liver tissue in control group and FB-/-group,and the percentage of macrophage infiltration was calculated.Results:The distances between normal colon tissue samples and CRC tissue samples,as well as between CRC tissue samples and CRC liver metastasis tissue samples were far,indicating significant differences between samples,allowing subsequent analysis of DEGs.A total of 1 908 DEGs were screened in the dataset comparing normal colon tissue samples and CRC tissue samples,including 771 up-regulated DEGs and 1 137 down-regulated DEGs.Twenty-three up-regulated DEGs and 100 down-regulated DEGs were identified in the dataset comparing CRC and CRC liver metastasis.The GO functional enrichment analysis results showed that compared with normal colon tissue samples,DEGs in CRC samples were mainly enriched in biological processes(BP)related to cell cycle and mitosis,including mitotic cell cycle process,cell division,response to hormone,mitotic nuclear division and response to lipid.Compared with CRC samples,the DEGs in CRC liver metastasis samples were mainly enriched in coagulation-related BP,including platelet degranulation,blood coagulation regulation,acute-phase response,hemostasis regulation and coagulation regulation.The KEGG pathway enrichment analysis results showed that compared with normal colon tissue samples,the DEGs in CRC tissue samples were mainly enriched in cell cycle and p53 signaling pathways.Compared with CRC tissue samples,the DEGs in CRC liver metastasis tissue samples were mainly enriched in complement,coagulation cascade and metabolism-related signaling pathways.The Hub genes identified in PPI network were related to blood proteins.The RT-qPCR results showed that compared with 0 d group,the mRNA expression level of complement related genes complement 1q(C1q)in liver metastatic foci tissue sampres in 7 d group was significantly decreased(P<0.05),the mRNA expression levels of complement 3(C3),complement 5(C5),FB,and factor D(FD)were significantly increased(P<0.05 or P<0.01),the mRNA expression levels of complement pathway-related genes C1q,complement 2(C2),C3,complement fragment 3a receptor(C3aR),C5,complement fragment 5a receptor(C5aR),decay-accelerating factor(DAF),FB and FD in liver metastatic foci tissue sampres in 14 d group were significantly increased(P<0.05 or P<0.01).Compared with control group,the liver weight of the mice in FB-/-group was significantly decreased(P<0.01),while there was no significant difference was observed in C4-/-group(P>0.05).The HE staining results showed that compared with control group,the liver metastatic foci in FB-/-mice were significantly decreased,and the percentage of metastatic area was decreased(P<0.01).The immunohistochemistry results showed that compared with control group,the macrophage infiltration in liver metastatic foci of the mice in FB-/-group was reduced,and the percentage of macrophage infiltration was decreased(P<0.01).Conclusion:Complement cascade is associated with CRC liver metastasis,and the alternative complement pathway regulates CRC liver metastasis,suggesting this pathway may serve as a potential therapeutic target for CRC liver metastasis.

Objective Jiedu Tongluo Tiaogan Formula(JTTF)is an effective formula for the clinical treatment of type 2 diabetes mellitus(T2DM).We used integrated pharmacology and in vitro experiments to explore the molecular mechanism of JTTF to improve insulin resistance(IR)in T2DM.Methods The drug targets of JTTF were obtained by identifying the key active ingredients of JTTF through UPLC-Q-TOF-MS.Multiple databases such as GeneCards,OMIM,and DrugBank were used to screen T2DM-IR related targets.Cytoscape software and String 11.0 database were used to construct the PPI network diagram of JTTF for T2DM-IR.GO and KEGG analyses were performed according to the Metascape platform to find the biological pathways related to the target proteins.AutoDock Tools software was used to simulate molecular docking.In vitro experiments were performed using palmitic acid(PA)-induced HepG2-IR cell model to detect the effect of JTTF on HepG2-IR.Results 28 effective active components of JTTF were screened.There were 857 gene targets of T2DM-IR,and 168 targets of drug-disease intersection.387 GO entries and 145 KEGG pathways were enriched.The molecular docking results showed that the main components of JTTF had good binding activities with PI3K and AKT-related proteins.The in vitro results showed that JTTF significantly alleviated PA-induced HepG2 cell injury,increased HepG2 glucose consumption,increased PI3K and AKT mRNA and protein expression,regulated the expression of GLUT2,GLUT4 and GSK3β,and improved cellular IR.Conclusion JTTF increases insulin sensitivity of HepG2-IR cells,promotes glucose uptake and intracellular glucose metabolism process,and its mechanism of action may be related to the up-regulation of PI3K/AKT signalling pathway.