Overexpression of wild-type HRAS drives non-alcoholic steatohepatitis to hepatocellular carcinoma in mice

Hepatocellular carcinoma(HCC),a prevalent solid carcinoma of significant concern,is an aggressive and often fatal disease with increasing global incidence rates and poor therapeutic outcomes.The etiology and pathological progression of non-alcoholic steatohepatitis(NASH)-related HCC is multifactorial and multistage.However,no single animal model can accurately mimic the full NASH-related HCC pathological progression,posing considerable challenges to transition and mechanistic studies.Herein,a novel conditional inducible wild-type human HRAS overexpressed mouse model(HRAS-HCC)was established,demonstrating 100%morbidity and mortality within approximately one month under normal dietary and lifestyle conditions.Advanced symptoms of HCC such as ascites,thrombus,internal hemorrhage,jaundice,and lung metastasis were successfully replicated in mice.In-depth pathological features of NASH-related HCC were demonstrated by pathological staining,biochemical analyses,and typical marker gene detections.Combined murine anti-PD-1 and sorafenib treatment effectively prolonged mouse survival,further confirming the accuracy and reliability of the model.Based on protein-protein interaction(PPI)network and RNA sequencing analyses,we speculated that overexpression of HRAS may initiate the THBS1-COL4A3 axis to induce NASH with severe fibrosis,with subsequent progression to HCC.Collectively,our study successfully duplicated natural sequential progression in a single murine model over a very short period,providing an accurate and reliable preclinical tool for therapeutic evaluations targeting the NASH to HCC continuum.

Mechanism of"Radix clematidis-impatientis semen"in the treatment of esophageal cancer based on network pharmacology

Objective:To explore the mechanism of“Radix clematidis-Impatientis semen”in the treatment of esophageal cancer based on network pharmacology.Methods:The active components of Radix clematidis and Impatientis semen were searched and selected through the TCMSP database,and supplemented with the literature,the targets of active components were predicted by Swiss Target Prediction platform.The main targets of esophageal cancer were obtained by Genecards,TTD and DisGeNet databases,and the key targets of“Radix clematidis-Impatientis semen”for the treatment of esophageal cancer were obtained by using Venn diagram analysis.The"drug-active ingredient-disease-target"network of“Radix clematidis-Impatientis semen”in the treatment of esophageal cancer was constructed with the help of Cytoscape3.7.2,and the key target PPI network was constructed by using STRING platform and Cytoscape software to find the core target.Metascape platform was used for GO and KEGG enrichment analysis of key targets,and the network diagram of"active componenttarget-pathway"was drawn.Results:There were 17 active components such as quercetin,kaempferol,3-epioleanolic acid and oleanolic acid in“Radix clematidis-Impatientis semen”,corresponding to 379 drug targets.178targets were obtained by mapping with 2396 disease targets of esophageal cancer,including PIK3CA,PIK3R1,SRC,MAPK1,MAPK3 and so on.KEGG enrichment analysis mainly involved PI3K-Akt,Rap1,Ras,VEGF signaling pathways,etc.Conclusion:This study preliminarily discusses the potential mechanism of“Radix clematidis-Impatientis semen”in the treatment of esophageal cancer,which provides a basis and new thought for further experimental research.

Study on prescription and medication rules of Hua Baojin for treatment of colorectal cancer based on data mining

Objective:To study the prescription and medication rule of Professor Hua Baojin in the treatment of colorectal cancer through data mining,so as to provide reference for clinical treatment of colorectal cancer. Methods:The outpatient medical records of Professor Hua Baojin from June 2015 to October 2020 in Guang’anmen Hospital,China Academy of Chinese Medical Sciences were collected. TCM Inheritance Support Platform(V2.5)was used to analyze high-frequency drugs,drug properties,flavors,channel tropism,common drug combinations,core combinations and new prescriptions. Results:A total of 500 prescriptions were included,involving 222 traditional Chinese medicines and 38 high-frequency(≥100)medicines,including Atractylodes,Poria cocos,ginger,etc. The most common medicinal properties of drugs were warm,cold and mild,and flavors were sweet,bitter and pungent,channel tropism included spleen,stomach,liver and lung meridians. 36 groups of common drug combinations and 20 association rules were obtained by data mining,and 18 core combinations and 9 new prescriptions were evolved.Conclusion:Professor Hua Baojin takes recuperating spleen and stomach as the core in the treatment of colorectal cancer,attaching importance to regulating the rise and fall of qi,adding and subtracting on the basis of Xiangsha Liujunzi Decoction,flexibly selecting the drugs of dispelling blood stasis,resolving phlegm,detoxification and loose knots,and using both cold and warm in the prescription,tonifying and reducing at the same time.

Study on the mechanism of“Salvia chinensis and Radix Ranunculi Ternati”drug pair in the treatment of lung cancer

Objective:To explore the molecular biological mechanism of the"salvia chinensis and radix ranunculi ternati"drug pair in the treatment of lung cancer based on network pharmacology.Methods:Searching the TCMSP database and previous literatures to screen the active compounds which resist lung cancer activity in salvia chinensis and radix ranunculi ternati.The candidate compounds were unified in the DrugBank to find the corresponding drug targets which were corrected to the standard gene names by the UniProt database.The Swiss Target Prediction platform was used to predict other targets.Searching GeneCards,OMIM and DrugBank to obtain genes related to lung cancer.After taking the intersection,the candidate gene target of drug pair in the treatment of lung cancer could be obtained.The"herbs-compounds-targets-disease"network was bulit with Cytoscape,and the PPI network was bulit on the STRING platform while the core network nodes were screened.GO and KEGG analysis on candidate genes was implemented through Metacape platform,and a"pathways-targets"network was bulit to further screen key genes.Results:A total of 16 active compounds in salvia chinensis,18 active compounds in radix ranunculi ternati,164 candidate targets,2443 GO functions and 170 KEGG pathways was obtained.Conclusion:The effective compounds of"salvia chinensis and radix ranunculi ternati"drug pair in the treatment of lung cancer are quercetin,ursolic acid,β-sitosterol and caffeic acid.The key targets are MAPK1,AKT1,PIK3R1,RAF1 and EGFR.GO functions mainly include cytokines,oxidative stress,plasma membrane transmission,protein kinase binding and activity,apoptosis.KEGG could directly regulate pathways in cancer,non-small cells lung cancer pathway and small cell lung cancer pathway.KEGG also involves EGFR tyrosine kinase inhibitor resistance,IL-17,TNF,PI3K-AKT signaling pathway and apoptosis.This study reveals the molecular biological mechanism of"salvia chinensis and radix ranunculi ternati"drug pair in the treatment of lung cancer.It is reasoned that its potential targets affect multiple signaling pathways and ultimately resist the proliferation,differentiation,invasion,metastasis and promote apoptosis of lung cancer cells.Evidence for further experimental study is provided by this study.