The establishment of mouse models is critical for discovering the biological targets of tumorigenesis and cancer development, preclinical trials of targeted drugs, and formulation of personalized therapeutic regimens. Currently, the patient-derived xenograft (PDX) model is considered a reliable animal tumor model because of its ability to retain the characteristics of the primary tumor at the histopathological, molecular, and genetic levels, and to preserve the tumor microenvironment. The application of the PDX model has promoted in-depth research on tumors in recent years, focusing on drug development, tumor target discovery, and precise treatment of patients. However, there are still some common questions. This review introduces the latest research progress and common questions regarding tumors with high mortality rates, focusing on their application in targeted drug screening and the formulation of personalized medical strategies. The challenges faced, improvement methods, and future development of the PDX model in tumor treatment applications are also discussed. This article provides technical guidance and comprehensive expectations for anti-cancer drug screening and clinical personalized therapy.

BACKGROUND:Bone marrow mesenchymal stem cells are one of the sources of adipocytes and express all renin-angiotensin system components,but the effect of angiotensin Ⅱ on bone marrow mesenchymal stem cell differentiation into brown adipose tissue is not clear.OBJECTIVE:To observe the effect of angiotensin Ⅱ on bone marrow mesenchymal stem cell differentiation into brown adipose tissue and investigate the role of angiotensin 1a receptor knockout in effect of angiotensin Ⅱ on bone marrow mesenchymal stem cell differentiation into brown adipocytes and its potential mechanisms.METHODS:After isolation and culture of bone marrow mesenchymal stem cells in wild-type and angiotensin 1a receptor knockout SD rats,the cells were cultured to the third generation and randomly divided into four groups:wild type group,knockout group,wild type+angiotensin Ⅱ group,and knockout+angiotensin Ⅱ group.The differentiation was induced in the brown fat induced differentiation medium for 14 days.Angiotensin Ⅱ(100 nmol/L)was added for intervention when the differentiation medium was changed each time in the latter two groups.Western blot assay,qRT-PCR,immunofluorescence,and other methods were used to detect the expression of induced differentiation,lipolysis,β oxidation,and mitochondrial biogenesis in brown fat.RESULTS AND CONCLUSION:Angiotensin Ⅱ could inhibit the browning of rat bone marrow mesenchymal stem cells.Knockout of angiotensin 1a receptor could improve the inhibitory effect of angiotensin Ⅱ on brown lipid formation of rat bone marrow mesenchymal stem cells by promoting lipolysis,enhancing fatty acid β oxidation,promoting mitochondrial biogenesis,and enhancing mitochondrial function.These findings provide new research directions and potential therapeutic targets for obesity treatment,revealing the important role of renin angiotensin systems in fat metabolism and its potential as a therapeutic target.

BACKGROUND:Bone marrow mesenchymal stem cells are one of the sources of adipocytes and express all renin-angiotensin system components,but the effect of angiotensin Ⅱ on bone marrow mesenchymal stem cell differentiation into brown adipose tissue is not clear.OBJECTIVE:To observe the effect of angiotensin Ⅱ on bone marrow mesenchymal stem cell differentiation into brown adipose tissue and investigate the role of angiotensin 1a receptor knockout in effect of angiotensin Ⅱ on bone marrow mesenchymal stem cell differentiation into brown adipocytes and its potential mechanisms.METHODS:After isolation and culture of bone marrow mesenchymal stem cells in wild-type and angiotensin 1a receptor knockout SD rats,the cells were cultured to the third generation and randomly divided into four groups:wild type group,knockout group,wild type+angiotensin Ⅱ group,and knockout+angiotensin Ⅱ group.The differentiation was induced in the brown fat induced differentiation medium for 14 days.Angiotensin Ⅱ(100 nmol/L)was added for intervention when the differentiation medium was changed each time in the latter two groups.Western blot assay,qRT-PCR,immunofluorescence,and other methods were used to detect the expression of induced differentiation,lipolysis,β oxidation,and mitochondrial biogenesis in brown fat.RESULTS AND CONCLUSION:Angiotensin Ⅱ could inhibit the browning of rat bone marrow mesenchymal stem cells.Knockout of angiotensin 1a receptor could improve the inhibitory effect of angiotensin Ⅱ on brown lipid formation of rat bone marrow mesenchymal stem cells by promoting lipolysis,enhancing fatty acid β oxidation,promoting mitochondrial biogenesis,and enhancing mitochondrial function.These findings provide new research directions and potential therapeutic targets for obesity treatment,revealing the important role of renin angiotensin systems in fat metabolism and its potential as a therapeutic target.

AIM:Chronic exposure to elevated levels of free fatty acids (FFAs) in type 2 diabetes patients is toxic to pancreatic β-cells.Thioredoxin (Trx)-interacting protein (TXNIP), an endogenous Trx-inhibiting protein, is up-regulated by glucose and is a critical mediator of hyperglycemia-induced β-cell apoptosis in diabetes.However, the effects of FFAs on TXNIP are unknown.In this experiment we observed the effect of palmitate on TXNIP expression in cultured INS-1 islet cells and the pathways involved were analyzed meanwhile.METHODS:After the full basis of preliminary experiment of incubating INS-1 cells with palmitate at different concentrations for different time, INS-1 islet cells were cultured with 0.5 mmol/L palmitate for 24 h.TXNIP expression, cell apoptosis, and expression of transcription factors related to TXNIP transcriptional regulation were determined.RESULTS:Compared with control group, the expression of TXNIP at mRNA and protein levels in palmitate group was significantly up-regulated (P<0.01).Cleaved caspase-3/caspase-3 ratio was increased in palmitate group (P<0.05), and the apoptosis of the INS-1 cells was also significantly increased (P<0.01).Palmitate enhanced the phosphorylation of nuclear factor-κB (NF-κB) (P<0.01), and the NF-κB inhibitors, PDTC and SN50, both blocked the palmitate-induced up-regulation of TXNIP expression.CONCLUSION:Saturated fatty acid palmitate enhances the expression of TXNIP.The mechanism of palmitate-induced TXNIP expression may be associa-ted with the increase in NF-κB phosphorylation.

AIM: To clarify the role of nitric oxide(NO) in ischemic preconditioning(IP) and its effects on apoptosis. METHODS: Seventy-two male Wistar rats were divided into the following six groups:ischemia/reperfusion (IR) group,IP group,IR+L-arg group,IP+L-arg group,IR+L-NAME group and IP+L-NAME group,The following changes were measured:cardiac hemodynamic parameters,infarct size,PMNs counting myocardial MPO activity and TUNEL staining.RESULTS: ①L-arg significantly attenuated ischemia/reperfusion-induced heart injury,reduced PMNs infiltration and cardiomyocyte apoptosis.②L-NAME also significantly reduced infarct size,PMNs infiltration and cardiomyocyte apoptosis compared with IR group,however,L-NAME aggravated ischemia/reperfusions-induced cardiac functional injury.③L-arg or L-NAME did not significantly alter the protective effect of ischemic preconditioning. CONCLUSION: Increased production of endogenous NO before prolonged ischemic period can protect hearts and inhibit apoptosis.L-NAME can inhibit iNOS activity and ONOO- production in reperfusion period to protect heart.