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Objective @#To study the molecular mechanism of fat mass and obesity⁃associated protein (FTO) regulating hepatocellular carcinoma (HCC) . @*Methods@#HepG2 cells of knock⁃down FTO were constructed , HepG2 cells of knock⁃down FTO and HepG2 cells were collected , and high⁃throughput sequencing was performed using Illumina Hiseq platform to screen the gene expression differences between the two groups . Through GO and KEGG enrichment analysis of these differential genes , FTO regulatory pathways were studied and downstream target genes of FTO were screened . The role of FTO downstream target gene in HCC was revealed by bioinformatic analysis and cell experiments .@*Results@#Transcriptome sequencing showed that 386 genes were differentially expressed between HepG2 cells of knock⁃down FTO and HepG2 cells , and they were involved in biological processes such as response to interferon⁃gamma . The expression of IFIT2 , one of the most responsive interferon⁃stimulating genes , was up⁃regulated after FTO knockdown . Potential m6 A methylation occurred at multiple sites of IFIT2 . The survival of HCC patients with high expression of IFIT2 was significantly prolonged , and knock⁃down of IFIT2 promoted the growth and migration of HepG2 cells . @*Conclusion @#FTO may regulate IFIT2 by mediating m6 A , and further promote the occurrence and development of HCC .
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Ferroptosis is an iron-dependent programmed cell death characterized by reactive oxygen species-induced lipid peroxide accumulation, which is different from cell apoptosis, pyroptosis, necrosis or autophagy. Ferroptosis plays an important role in the regulation of tumorigenesis and tumor development. Recent studies have shown that natural medicinal ingredients can induce ferroptosis in tumor cells through glutathione (GSH)/glutathione peroxidase 4 (GPx4) pathway, iron metabolism, lipid metabolism or other mechanisms. It has been reported that more than 30 natural medicinal ingredients can induce ferroptosis in tumor cells with multiple pathways and multiple targets. This article reviews the current research progress on the antitumor effects of natural medicinal ingredients through inducing cell ferroptosis.
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Humans , Apoptosis , Autophagy , Ferroptosis , Neoplasms/drug therapy , Reactive Oxygen SpeciesABSTRACT
; Aim To study the synergistic inhibition effect of hydroxychloroquine (HCQ) and bevacizumab (B E V) on the cell growth of HUVECs and its mechanism. Methods RTCA,flow apoptosis assay and the vascularization assay of HUVECs were used to study the effect of HCQ combined with BEV on HUVEC proliferation, cell apoptosis and vascularization. The expressions of LC3 and p62 proteins were detected by Western blot, autophagy flow was observed through m Cherry EGFPLC3 double fluorescence, the changes of autophagosome and mitochondria were observed by electron microscopy, and the regulatory molecular mechanism of HCQ combined with BEV was revealed by transcriptome sequencing (RNA-seq). Results Compared with single drug groups, the combination of HCQ and BEV could synergistically inhibit HUVEC proliferation, promote HUVEC apoptosis, and inhibit the formation of vascular structures in HUVECs. HCQ could inhibit autophagy of HUVECs. Transcriptome sequencing results showed that the combination of HCQ and BEV influenced 69 different expressed genes,and the combination of HCQ and BEV might synergistically inhibit HUVECs by regulating "hub" genes such as RICTOR and PIK3CA. Conclusions The combination of HCQ and BEV can synergistically inhibit HUVECs, which is related to not only the inhibition of autophagy by HCQ, but also the regulation of " hub " genes such as RICTOR and PIK3CA.
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Pace of life and work of people is accelerating nowadays, and hospitals keep improving their services, which gives rise to the decoction and delivery service from the third party vendors for traditional Chinese medicine(TCM).Given the quality control standards for the TCM decoction service as issued by Zhejiang and other regions, the systems of supervision and assessment remain incomplete.Authors of the paper introduced a project improvement team, composed of Chinese medicine pharmacy, Chinese medicine experience specialists, vendors of Chinese medicine decoction and express delivery companies, hence establishing a " three-in-one" supervision system of Internet+TCM decoction and delivery service. This practice can optimize the assessment indexes, strengthen the assessment system of assessment transformation and supervision system for patient medication.It proves that the practice contributes to higher quality and safety of TCM decoction and delivery service, improves the ability and level of TCM services, and ensures the medication safety of patients.
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Objective To study the effect of matrine on Calpain and MAP-2 in rats with experimental autoimmune encephalomyelitis(EAE).Methods In accordance with the random number table ,60 Wistar rats were divided into 6 groups randomly: normal group,model group,dexamethasone(DEX)-treated group(1mg/kg),high-dose matrine(MAT)-treated group(250mg/kg),middle-dose MAT-treated group(200mg/kg) and low-dose MAT-treated group(150mg/kg).The EAE models were induced by immunized spinal cord extracts of guinea pig with complete Freunds'adjuvant.Rats of three MAT-treated groups and DEX-treated group were injected intraper-itoneally with MAT and DEX daily for 16 days respectively,whereas rats of normal group and model group were injected intraperitoneally with normal saline.Clinical signs of rats in six groups were observed daily .Hematoxylin-eosin (HE) was used to analyze histopathological evaluation of spinal cord .μ-Calpain,m-Calpain and MAP-2 in spinal cord were determined using RT-PCR and immunohistochemistry respectively .Results Compared with the model group[(2.85 ±0.78)points],the clinical scores were significantly decreased in high-dose-MAT group[(1.28 ± 0.59) points], middle-dose-MAT group [(1.45 ±0.64) points] and low-dose-MAT group [(2.09 ± 0.71)points](t =5.345,4.314,2.869,all P <0.05).The HE score of rats in model group[(2.49 ±0.29)points] was significantly higher than that in high-dose-MAT group[(1.04 ±0.26) points],middle-dose-MAT group [(1.29 ±0.20) points] and low-dose-MAT group[(1.77 ±0.24)points] (t =5.185,4.274,3.629,all P <0.01).The levels of μ-Calpain mRNA and m-Calpain mRNA in the three MAT-treated groups were significantly lower than those in model group(t =10.656,9.418,7.044,all P <0.01;t =6.332,5.416,3.978,all P <0.01).In addition,the expression of MAP-2 in the spinal cord of EAE rats showed a marked elevation after MAT treatment (t =12.841,9.924,7.038,all P <0.01).Conclusion Matrine may be an effective therapeutic approach for EAE by inhibiting Calpain and increase MAP-2 expression.
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Metabolism has been a focus of cancer research in the last few years,and researchers have found that many pathways associated with tumor growth were related to metabolic pathways.The ketogenic diet (high fat,low carbohydrate and protein) caused metabolic changes,such as a reduction in blood glucose and an increase in blood ketones.Findings indicated that ketogenic diet could reduce the energy for cancer cells and inhibit tumor growth;furthermore,it did not significantly affect the energy metabolism and physiology of body.To date,ketogenic diet is considered as an anti-angiogenic,anti-metastatic and pro-apoptotic metabolic therapy,and the metabolic therapy has the potential to improve the outcome of patients with glioblastoma multiforme and other malignant brain cancers.In this review,we discuss the research progresses about anti-brain tumor effect ofketogenic diet and its related mechanism.