Exploring the mechanism of action of herb pair Pinellia Ternata-Magnolia Officinalis in the treatment of liver cancer based on network pharmacology and molecular docking

Background:Explore the anti-tumor mechanism of herb pair Pinellia ternate-Magnolia officinalis(BX-HP)in liver cancer through network pharmacology using molecular docking methods.Method:The active ingredients and corresponding targets of the herb pair Pinellia ternate-Magnolia officinalis were obtained from the HERB database.The relevant targets for liver cancer were obtained from GeneCards,DisGeNET,TTD,and Drugbank databases.Obtain common targets between herb pair Pinellia ternate-Magnolia officinalis and liver cancer through the Bioinformatics platform,establish a PPI network diagram using STRING software,and perform GO functional enrichment and KEGG pathway enrichment analysis on the DAVID platform.AutoDockTools 1.5.7 software and molecular dynamics simulation analysis are used to evaluate the binding of components to target proteins.HERB database,SwissTargetPrediction database,SwissADME database,UniProt database,GeneCards database,TTD database,DRUGBANK database,DisGeNET database,String,DAVID.Bioinformatics platform,PDB database,PubChem and TCMSP database.Result:A total of 22 active ingredients with a Probability>0.1 targets in Magnolia officinalis were screened,26 active ingredients with a Probability>0.1 targets in Pinellia ternata,ten vital active ingredients,corresponding to 979 and 803 targets with a Probability>0.1 targets,2536 liver cancer-related targets,and 279 targets in the herb pair Pinellia ternata-Magnolia officinalis.The GO functional enrichment analysis resulted in 1297 entries,namely 971 biological process entries,118 cell localization entries,and 208 molecular function entries.Three signaling pathways were annotated through the KEGG pathway.Based on molecular docking,ten vital active ingredients and five target proteins were validated to exhibit an excellent binding affinity.The above data indicates that combining the herb pair Pinellia ternata-Magnolia officinalis may treat liver cancer through specific targets and signaling pathways.Conclusion:Herb pair Pinellia ternata-Magnolia officinalis has a synergistic effect on treating liver cancer through multicomponent,multitarget,and multi-pathway approaches.This study provides a sufficient theoretical basis for subsequent research.

TRAIL-induced expression of uPA and IL-8 strongly enhanced by overexpression of TRAF2 and Bcl-xL in pancreatic ductal adenocarcinoma cells

BACKGROUND:The death ligand,tumor necrosis factor(TNF)related apoptosis-inducing ligand(TRAIL),induces apoptosis and non-apoptotic signaling in some tumor cells.The purpose of this study was to investigate the roles of the pro-apoptotic TRAIL receptors,TRAIL-R1 and TRAIL-R2,as well as Bcl-xL and TRAF2 in TRAIL-induced expression of the pro-inflammatory cytokine IL-8 and the invasion-promoting protein urokinase(uPA) in pancreatic ductal adenocarcinoma(PDAC) cells.METHODS:Colo357wt,Colo357/TRAF2,Colo357/Bcl-xL,Panc89 and PancTuI cells were stimulated with TRAIL and uPA and IL-8 expression was detected using real-time PCR.Antagonistic,receptor-specific antibodies were used to investigate the effects of TRAIL-R1 or TRAIL-R2 inhibition.RESULTS:Dose-dependent increases in uPA and IL-8 expression were detected following TRAIL stimulation in PDAC cells.These effects were inhibited when TRAIL-R1 but not TRAIL-R2 was blocked.Overexpression of TRAF2 or Bcl-xL strongly increased TRAIL-mediated upregulation of uPA and IL-8.CONCLUSIONS:In PDAC cells,TRAIL strongly induced uPA and IL-8 via TRAIL-R1.This response was further enhanced in cells overexpressing TRAF2 and Bcl-xL.Therefore,inhibition of the non-apoptotic "side-effects" of TRAIL treatments by inactivation of TRAF2 and Bcl-xL might represent additional relevant strategies for the treatment of pancreatic cancer.

NKX3．1对前列腺癌PC3细胞中IGF—IR的表达及其信号转导通路的抑制作用研究

NKX3.1, which is a prostate-specific homeobox gene, plays an important role in prostate cancer and usually functions as a tumour suppressor gene. In this study, we investigated the inhibitory effect of NKX3,1 on insulin-like growth factor （IGF）- 1R expression and its downstream signalling pathway in PC3 cells, PC3 cells were stably transfected with NKX3.1 expression plasmid （pcDNA3.1-NKX3.1） or vector plasmid （pcDNA3.1＋）. The IGF-IR mRNA and protein expression levels were assessed in PC3-NKX3.1 transfectants by reverse transcriptase-polymerase chain reaction （RT-PCR） and Western blotting. The expression and activation of IGF-1/IGF-1R downstream signalling targets were examined by Western blotting and luciferase reporter assay. The cells were subsequently treated with relevant concentrations of IGF-1. The effect of IGF-1 on cell growth was examined by 3-（4,5）-dimethylthiahiazo（-z-yl）-3, 5-diphenytetrazoliumromide （MTT） assay and flow cytometry analysis. A significant suppression of IGF-1R mRNA and protein expression was observed after forced expression of NKX3.1 in PC3 cells. Correspondingly, the forced expression of NKX3.1 decreased IGF-l-induced phosphorylation of extracellular signal-regulated kinase 1/2 （ERK1/2） and protein kinase B （AKT） and activation of the Elk-1 transcription factor and downregulated the expression of the downstream target genes c-fos and cyclin D1. Furthermore, the forced expression of NKX3.1 inhibited IGF-l-induced cell growth. In conclusion, NKX3.1 could downregulate IGF-1R expression and could inhibit IGF-1R-mediated mitogen-activated protein kinase （MAPK）/ERK and AKT signalling pathways, which might partially leads to the inhibition of IGF-l-induced cell growth. This study provides new insights into the molecular mechanisms that NKX3,1 exerts against prostate cancer and ultimately expands the scope of alternative approaches in advanced prostate cancer therapy.

Behcet’s disease manifesting as esophageal variceal bleeding: A case report

BACKGROUND Behcet’s disease(BD)is a chronic disease characterized by oral and vulvar ulcers as well as eye and skin damage and involves multiple systems.It presents as an alternating process of repeated attacks and remissions.Esophageal venous rupture and bleeding caused by BD is rarely reported at home and abroad.This paper reports a case of bleeding from oesophageal varices caused by BD,aiming to provide an additional dimension for considering the cause of bleeding from esophageal varices in the future.CASE SUMMARY A 38-year-old female patient was admitted due to a gradual increase in shortness of breath and chest tightness after the activity,and was admitted to our hospital for treatment.After admission,relevant examinations showed that the patient had multiple blood clots.Four days after admission,she suddenly experienced massive hematemesis.Emergency esophagogastroduodenoscopy revealed bleeding from esophageal and gastric varices.The patient had no history of viral hepatitis or drinking habits,and no history of special genetic diseases or congenital vascular diseases.There is no obvious abnormality in liver function.After reviewing the medical history,it was found that the patient had recurred oral ulcers since childhood,ulcers were visible in the perineum during menstruation,and there was an intermittent red nodular rash and uveitis.The current skin acupuncture reaction is positive,combined with the evaluation of the external hospital and our hospital,the main diagnosis is BD.She received methylprednisolone,cyclophosphamide,immunomodulation,acid suppression,gastric protection,and anticoagulation and anti-infection treatments,and was discharged from the hospital.During the 1-year follow-up period,the patient did not vomit blood again.CONCLUSION This case highlights bleeding from esophageal varices caused by BD, aiming toprovide an additional dimension concerning the cause of bleeding fromesophageal varices in the future.

Cetirizine regulates scleroderma skin fibrosis in mice via the TGF-β1/Smad3 signaling pathway

Objective:To investigate the effect of cetirizine on the fibrosis of skin tissue in systemic sclerosis(SSc)mice and its mechanism of action.Methods:Thirty-two BALB/C mice were randomly divided into a blank group,a model group,a cetirizine low-dose group,and a cetirizine high-dose group,with eight in each group.The blank group was injected with normal saline on the back,and the other three groups were injected with bleomycin on the back to prepare SSc mouse models.The mice were injected once a day for 28 consecutive days,while the normal group and the model group were given saline.The dose group was administrated intragastrically at 2 mg/kg and 5 mg/kg,respectively,for 28 consecutive days.Detect the thickness of the dermis by taking the skin tissue in the back injection area of each group.Hematoxylin-eosin staining(HE)and Masson staining.Sample hydrolysis method to detect hydroxyproline(HYP)content in skin tissue.Immunohistochemical detection ofα-smooth muscle actin(α-SMA)expression in skin tissues.Enzyme-linked immunosorbent assay(ELISA)to detect serum interleukin(IL-6,IL-10)and transforming growth factor(TGF-αand TGF-β1).Quantitative real-time PCR(qRT-PCR)was used to detect the expression levels of collagen type I(COL1A1),type III collagen(COL3A1),Smad homolog 3(Smad3),and TGF-β1 mRNA.Western blot was used to detect the expression levels of COL1A1,COL3A1 and p-Smad3.Results:Compared with the blank group,the dermis thickness and HYP content of the model group increased,the skin tissue lesions and fibrosis were more severe,theα-SMA positive expression intensity in the skin tissue was higher,and the serum IL-6,IL-10,TGF-α,TGF-β1 content increased,COL1A1,COL3A1,Smad3,TGF-β1 mRNA expression levels increased in skin tissues,COL1A1,COL3A1,p-Smad3 protein expression increased,the differences were statistically significant(P<0.05).Compared with the model group,the dermal thickness and HYP content of the low and high dose cetirizine groups were reduced,the degree of skin tissue lesions and fibrosis was improved,the expression ofα-SMA in skin tissues was weakened,the levels of IL-6,IL-10,TGF-α,TGF-β1 in serum were reduced,the expression levels of COL1A1,COL3A1,Smad3 and TGF-β1 in skin tissues were reduced,and the expression levels of COL1A1,COL3A1,and p-Smad3 proteins were reduced,the decrease in the high-dose group was more significant,and the differences were statistically significant(P<0.05).Conclusion:Cetirizine can improve the degree of fibrosis of skin tissue in SSc mice and reduce the immune inflammation response.The mechanism of action is related to the TGF-β1/Smad3 signaling pathway.

Effect of Yangxinshi Tablets on the Phenotype and Function of Monocytes in Patients with Unstable Angina Pectoris of Coronary Heart Disease

Objective:The objective of this study was to observe the effect of Yangxinshi tablets on the phenotype and function of peripheral blood monocytes in patients with unstable angina of coronary heart disease(CHD)and to explore the possible mechanism of Yangxinshi tablets in the treatment of CHD.Methods:A total of 100 patients with unstable angina of CHD were randomly divided into two groups:Group A–treatment group and Group B–control group.The phenotypic and functional changes in blood monocytes and the changes in serum inflammatory factors before and after treatment were compared in the two groups.Results:The expression of CD14^+CD163^+interleukin(IL)-10^+was significantly higher in the control group than in the patients with unstable angina of CHD,whereas the expression of CD14^+CD163-IL-12^+was lower.The concentration of IL-10 was higher in the control group than in the patients with unstable angina,whereas the concentration of tumor necrosis factor-α(TNF-α)and IL-12 was significantly lower.In Group A,the expression of CD14^+CD163^+,CD14^+CD206^+,and CD14^+CD163^+CD206^+in peripheral blood monocytes increased after treatment than before treatment,whereas the expression of CD14^+CD163-CD206-decreased.The expression of CD14^+CD163-IL-12^+decreased after treatment than before,whereas CD14^+CD163^+IL-10^+expression increased.The serum concentration of IL-10 in Group A was higher after treatment than before,whereas that of IL-12 and TNF-αwas lower.In Group B,the phenotype and function of the peripheral blood monocytes remained unchanged.Conclusion:Yangxinshi tablet therapy can change the phenotype of the peripheral blood monocytes in patients with unstable angina of CHD.Yangxinshi tablet therapy changes the inflammatory state in patients with an increase in the expression of anti-inflammatory factors and a decrease in the expression of inflammatory factors.

Monitoring Damage Evolution in a Titanium Matrix Composite Shaft Under Torsion Loading Using Acoustic Emission

The damage behaviors of a titanium matrix composite shaft under torsion loading were monitored using the acoustic emission technique. The composite shaft with SiC fibers at ±45° orientations was prepared by the solid-state fabrication process. Both the torsional rigidity and torsional strength of the TMC shaft were improved by SiC fibers. The acoustic emission responses during the loading-unloading-reloading, under quasi-static and cyclic torsion tests were investigated. Multiple acoustic emission signals were grouped as mechanical noise, matrix deformation, interface debonding and fiber fracture using amplitude, waveform shape and frequency centroid parameters. A substantial reduction of signals generated by matrix deformation was found in the reloading test. During the quasi-static torsion test, interface debonding and progressive breaks of SiC fibers occurred. According to different acoustic emission behaviors, the failure process in the torsion fatigue test can be divided into three stages: the initial stage, the fiber fracture stage and the fast fracture stage.