A novel traditional Chinese medicine combination for radiation

Objective:To formulate an efficacious radioprotective combination of Chinese medicines with minimal toxicity.Methods:Aqueous and alcoholic extracts from 38 traditional Chinese herbs were prepared.To produce drugcontaining sera,rats received six doses of each extract via oral gavage at 12-h intervals.Subsequently,human lung epithelial BEAS-2B cells were cultured in these drug-containing sera.The cell viability was assessed after different doses of irradiation to identify the radioprotective effects of Chinese herbal extracts.The efficacy of a selected Chinese herbal extract combination was further confirmed through cell viability analysis via in vitro colony formation and survival rate assessments in C57BL/6 mice post-irradiation.Results:Extracts from Angelicae Sinensis Radix(ASR;two extracts),Citri Reticulatae Pericarpium(CRP),Platycladi Cacumen(PC),Schisandrae chinensis Fructus(SF),Scutellariae Radix(SR),and Glycyrrhizae Radix et Rhizome(GRR)demonstrated radioprotective effects.The combination of the seven Chinese herbal extracts notably increased the survival and viability of the BEAS-2B cells exposed to varying doses of X-rays.Moreover,the group of mice receiving Chinese medicine combination and irradiation exhibited prolonged survival after exposure to 6.5 Gy Xrays with a median survival of(14=2)d compared to(11=2)d in the irradiated group without the herbal treatment.Additionally,the Chinese medicine combination group displayed a significantly higher 28 d survival rate(30%)compared to the irradiation-only group(16.6%,P<0.05).Conclusion:The novel combination of Chinese herbal extracts from ASR,CRP,PC,SF,SR,and GRR has the potential for radiation protection applications.

Changes of gut microbiome and metabolome in the AOM/DSS mouse model of colorectal cancer with FLASH radiation

Objective:To investigate the differences in small intestinal toxicity and taxonomic composition,diversity,and functional pathways of gut microbiome and metabolome after different radiotherapies in mouse colorectal cancer(CRC)model.Methods:Azoxymethane/dextran sodium sulfate(AOM/DSS)-induced mouse CRC model was treated with single pulse FLASH-RT(dose rate 100 Gy/s)or CONV-RT(dose rate 2 Gy/min)at whole abdomen.At 12 d after radiotherapy,sections of small intestinal tract tissue were dissected for hematoxylin and eosin(HE)staining and the fresh feces were collected for 16S ribosomal RNA(rRNA)microbiome sequencing and liquid chromatography and mass spectrometry(LC-MS)metabolomics sequencing to assess changes in the gut microbiota and metabolites.Microbial high-throughput 16S rRNA data was analyzed with QIIME2 and LEfSe softwares.ProteoWizard,XCMS and Ropls softwares were used for LC-MS analysis.Results:HE staining showed that FLASH-RT maintained small intestinal integrity and reduced the radiotherapyinduced injury.Sequencing analysis of gut fecal microbiome showed that phylum Bacteroidetes and genera Prevotella and Lactobacillus of microbial community were increased after FLASH-RT.Metabolomics sequencing analysis revealed that the metabolites after FLASH-RT were enriched in amino acid metabolism,while cholesterol metabolism was top enriched after CONV-RT.Conclusions:FLASH-RT significantly mitigates the small intestine tissue damage compared with CONV-RT.FLASHRT and CONV-RT have different impact on gut microbiota and its metabolites.Our results provide a theoretical basis for the early evaluation,prediction and individualized treatment of the irradiation effect after novel FLASHRT on tumors through the evaluation of intestinal microbiota and metabolites.

Progress in tumor vascular normalization for anticancer therapy:challenges and perspectives

Antitumor angiogenic therapy has been shown promising in the treatment of several advanced cancers since the approval of the first antiangiogenic drug Avastin in 2004.Although the current antiangiogenic drugs reduce the density of tumor blood vessels and result in tumor shrinkage at the early stage of treatment,recent studies have shown that antiangiogenic therapy has transient and insufficient efficacy,resulting in tumor recurrence in patients after several months of treatment.Blockage of blood and oxygen supplies creates a hypoxic and acidic microenvironment in the tumor tissues,which fosters tumor cells to become more aggressive and metastatic.In 2001,Jain proposed tumor vascular normalization as an alternative approach to treating cancers based on the pioneering work on tumor blood vessels by several other researchers.At present,normalizing the disorganized tumor vasculature,rather than disrupting or blocking them,has emerged as a new option for anticancer therapy.Preclinical and clinical data have shown that tumor vascular normalization using monoclonal antibodies,proteins,peptides,small molecules,and pericytes resulted in decreased tumor size and reduced metastasis.However,current tumor vascular normalizing drugs display moderate anticancer efficacy.Accumulated data have shown that a variety of vasculogenic/angiogenic tumor cells and genes play important roles in tumor neovascularization,growth,and metastasis.Therefore,multiple-targeting of vasculogenic tumor cells and genes may improve the efficacy of tumor vascular normalization.To this end,the combination of antiangiogenic drugs with tumor vascular normalizing therapeutics,as well as the integration ofWestern medicine with traditional Chinese medicine,may provide a good opportunity for discovering novel tumor vascular normalizing drugs for an effective anticancer therapy.