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OBJECTIVE@#To investigate the potential mechanisms that mediate the inhibitory effect of porcine recombinant NKlysin (prNK-lysin) against liver cancer cell metastasis.@*METHODS@#HPLC-tandem mass spectrometry was used to identify the differentially expressed proteins in prNK-lysin-treated hepatocellular carcinoma SMMOL/LC-7721 cells in comparison with the control and PBS-treated cells. GO functional annotation and KEGG pathway analysis of the differentially expressed proteins were performed using GO and KEGG databases. RT-qPCR was used to determine the mRNA expression levels of polypeptide-N-acetylgalactosaminotransferase 13 (GALNT13), transmembrane protein 51 (TMEM51) and FKBP prolyl isomerase 3 (FKBP3) in the cells, and the protein expression of FKBP3 was verified using Western blotting.@*RESULTS@#Proteomic analysis identified 1989 differentially expressed proteins in prNK-lysin-treated cells compared with the control cells, and 2753 compared with PBS-treated cells. Fifteen proteins were differentially expressed between PBS-treated and the control cells, and 1909 were differentially expressed in prNK- lysin group compared with both PBS and control groups. These differentially expressed proteins were involved mainly in the viral process, translational initiation and RNA binding and were enriched mainly in ribosome, protein process in endoplasmic reticulum, and RNA transport pathways. RT-qPCR showed that compared with the control group, prNK-lysin treatment significantly increased the mRNA expressions of GALNT13 (P < 0.05) and TMEM51 (P < 0.01) and lowered FKBP3 mRNA expression (P < 0.05). Western blotting also showed a significantly decreased expression of FKBP3 protein in prNK-lysin-treated cells (P < 0.001).@*CONCLUSION@#Treatment with prNK-lysin causes significant changes in protein expression profile of SMMOL/LC-7721 cells and inhibits hepatocellular carcinoma metastasis by downregulating FKBP3 protein and affecting the cellular oxidative phosphorylation and glycolysis pathways.
Subject(s)
Animals , Swine , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Oxidative Phosphorylation , Proteomics , Glycolysis , RNA, MessengerABSTRACT
Organoids are three-dimensional cellular structures with self-organizing and self-differentiation capacities. They faithfully recapitulate structures and functions of in vivo organs as represented by functionality and microstructural definitions. Heterogeneity in in vitro disease modeling is one of the main reasons for anti-cancer therapy failures. Establishing a powerful model to represent tumor heterogeneity is crucial for elucidating tumor biology and developing effective therapeutic strategies. Tumor organoids can retain the original tumor heterogeneity and are commonly used to mimic the cancer microenvironment when co-cultured with fibroblasts and immune cells; therefore, considerable effort has been made recently to promote the use of this new technology from basic research to clinical studies in tumors. In combination with gene editing technology and microfluidic chip systems, engineered tumor organoids show promising abilities to recapitulate tumorigenesis and metastasis. In many studies, the responses of tumor organoids to various drugs have shown a positive correlation with patient responses. Owing to these consistent responses and personalized characteristics with patient data, tumor organoids show excellent potential for preclinical research. Here, we summarize the properties of different tumor models and review their current state and progress in tumor organoids. We further discuss the substantial challenges and prospects in the rapidly developing tumor organoid field.
Subject(s)
Humans , Neoplasms/genetics , Organoids/pathology , Carcinogenesis , Models, Biological , Precision Medicine/methods , Tumor MicroenvironmentABSTRACT
The method of scoping review was used to systematically search and sort out the clinical research of oral Chinese patent medicines for ischemic stroke，to understand the scope of relevant research and the distribution of evidence. Three medical catalogs were manually searched to obtain the oral Chinese patent medicines used for ischemic stroke，and 7 databases were retrieved to obtain the clinical research including these oral Chinese patent medicines. Then the clinical evidence results were visualized by description combined with chart analysis. A total of 68 oral Chinese patent medicines were retrieved，and 1 392 articles were included，with 367 published in core journals， involving 35 oral Chinese patent medicines. The research types included randomized controlled trials，cohort studies，case series，case reports，secondary studies，adverse drug reaction reports，pharmacoeconomic evaluations，drug interactions，consensus or guidelines，non-randomized intervention studies and cross-sectional studies，of which randomized controlled trials had the largest number （283， 77.1%），followed by secondary studies and case series （25， 6.7% for each）. Among the 283 randomized controlled trials，there were 159 clinical studies in the acute phase of ischemic stroke，65 in the non-acute phase，and 59 in the unclear phase. Ten intervention control types and 20 outcome index types were summarized. Among them， the composite outcome index and surrogate outcome index were used 217 times （76.7%） and 245 times （86.6%）， respectively，followed by the degree of neurological impairment （three scales）. Future clinical research of oral Chinese patent medicines for ischemic stroke should clarify the stage of the disease，and the research design should specify the advantages of oral Chinese patent medicines intervening in ischemic stroke. Furthermore， publicly-recognized positive controls should be employed，and important clinical outcome indexes should be selected.
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Objective To explore the effect of neural cell adhesion molecule (NCAM) on adhesion,migration and morphology of mouse bone marrow-derived mesenchymal stem cells (BMSCs).Methods We isolated and cultured BMSCs from wild-type and NCAM gene knockout mice.The expression of NCAM was detected by Western blot and immunofluorescence.Wound healing and adhesion assays were used to detect cell migration and adhesion ability respectively.The morphological changes were observed and the expressings of protein β1 integrin,E-cadherin,β-catenin and N-cadherin were analysed by Western blot.Results The migration and adhesion of BMSCs were significantly reduced after NCAM gene knockout.Meanwhile,the expression of β1 integrin was lower than those in wild-type BMSCs (P<0.01).The morphology of NCAM gene knockout BMSCs changed from irregular to flattened,and expressed epithelial identification marker E-cadherin and β-catenin (P<0.05).However,the expression level of mesenchymal identification marker N-cadherin was decreased (P<0.01).Conclusions NCAM is involved in adhesion and migration of BMSCs via regulating the expression of β1 integrin.Furthermore,NCAMmay negatively regulate the mesenchymal-epithelial transitions of BMSCs.
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Objective To discuss the methods of the heat preservation performance monitoring of the blood transport case and to provide the technical support for the safety of blood transportation.Methods At the different environment temperature,the amount of the cold resource was decided by the mass ratio of cold resource to blood and the temperature was automatically recorded by the intelligent temperature chip continuously,to monitor the changes of each monitoring point in the blood transport case.Results When the mass ratio of cold resource to blood was fixed at 1∶6,the cold chain of the blood transport case could keep the tempera-ture of 2-10 ℃ for 8 hours at the environment temperature of 12 ℃,It could keep the temperature of 2-10 ℃ for 4.5 hours at the environment temperature of 25 ℃,and it could keep the temperature of 2-10 ℃ for 2 hours at the environment temperature of 44℃.Conclusion When the mass ratio of cold resource to blood is fixed,as the environment temperature changes,the available time that the blood transport case keeps with the cold-chain requirement varies according to the results of the heat preservation per-formance monitoring of the blood transport case.
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Objective: To investigate the clinical efficacy of acupuncture combined with tuina in treating patients with cervical vertigo. ＜br> Methods: According to the principle of randomization, 258 cases with cervical vertigo who met the inclusion criteria for the study were randomly divided into an observation group and a control group, with 129 cases in each. The patients in the observation group received acupuncture combined with tuina therapy, while those in the control group were just treated by the same acupuncture therapy as in the observation group. After 10-day continuous treatments, the clinical efficacies of the two groups were analyzed and compared. ＜br> Results: The total effective rate of the observation group was 100%, versus 86.0% of the control group, and the difference was significant (P＜0.05). After treatment, cervical range of motion (ROM) scores in both groups were statistically significantly different from those before treatment (allP＜0.05); in addition, there was a statistically significant difference in inter-group comparison of ROM score (P＜0.05). ＜br> Conclusion: Compared with simple acupuncture treatment, acupuncture combined with tuina therapy has a better effect in improving the ROM of cervical vertigo patients, with higher clinical efficacy.
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Objective To explore the therapeutic effect of Han-uvulopalatopharyngoplasty (H-UPPP) combined with coblation on treatment of type Ⅱ mild and moderate obstructive sleep apnea hypopnea syndrome (OSAHS).Methods According to the measuring parameters analyzed and clinical characteristics of velopharyngeal,68 patients were divided into 3 groups:group A (28 patients,treated by H-UPPP combined with coblation of tonsillectomy),group B (22 patients,treated by H-UPPP combined with drilling of tonsil) and group C (18 patients,treated by velopharyngeal multi-points drilling).After operation for 6 months,the pafor tients in 3 groups were detected by the polysomnography (PSG),Epworth sleepiness scale,and the parameters of velopharyngeal were compared.Results After operation for 6 months,the heal,excellence,efficiency and inefficiency patients in group A were 6,10,7,5 cases,in group B were 3,8,7,4 cases,in group C were 2,7,5,4 cases,there was no significant difference (P ＞0.05).After operation for 6 months,the apnea hyponea index (AHI) and the scores of ESS in group A,B,C were significantly lower than those before operation [(10.1 ± 2.3) times/h vs.(21.2 ± 2.5) times/h,(6.4 ± 1.0)scores vs.(16.2 ± 1.0) scores,(6.9 ± 1.3) times/h vs.(16.0 ± 1.4) times/h,(5.4 ± 1.3) scores vs.(14.5 ±1.5) scores,(7.7 ± 1.8) times/h vs.(16.0 ± 2.1) times/h,(4.1 ± 1.0) scores vs.(12.3 ± 1.9) scores],thelevel of LSaO2 was significantly higher (0.885 ±0.035 vs.0.737 ±0.030,0.871 ±0.046 vs.0.763 ±0.033,0.901 ±0.029 vs.0.820 ±0.034),there was significant difference (P ＜0.01),but there was no significant difference among 3 groups (P ＞ 0.05).After operation for 6 months,the pharyngomaxillary space,distance between uvula and posterior wall of pharynx,distance between anterior pillars in group A,B,C were significantly increased compared with those before operation [(24.6 ± 0.9) mm vs.(12.3 ± 1.2)mm,(11.6 ±1.2) mm vs.(5.4 ± 0.6) mm,(34.9 ± 1.2) mm vs.(28.3 ± 1.0) mm,(24.0 ± 0.8) mm vs.(14.3 ± 1.0) mm,(11.8 ± 0.8) mm vs.(6.3 ± 0.4) mm,(38.3 ± 0.8) mm vs.(31.9 ± 1.9) mm,(23.6 ± 1.4) mm vs.(19.9 ±1.1) mm,(7.3 ± 0.5) mm vs.(6.8 ± 0.6) mm,(38.5 ± 0.8) mm vs.(35.2 ± 1.0) mm],the length of soft palate was decreased [(31.9±0.9) mm vs.(38.3 ±0.9) mm,(25.6 ± 1.0) mm vs.(35.6 ± 1.2) mm,(29.9 ± 1.3) mm vs.(34.9 ±0.9) mtm],there was significant difference (P ＜0.01),but there was no significant difference among 3 groups (P ＞ 0.05).Conclusions H-UPPP combined with coblation on treatment of type Ⅱ mild and moderate OSAHS is effective and safe.According to the clinical characteristics of the patients to select suitable method is the key to get a satisfactory curative effect.
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OBJECTIVE To study the best surgical technique for treatment of chronic hypertrophic rhinitis(HR).METHODS Eighty six cases with HR were divided randomly into 3 groups.Thirty cases were treated by transnasal endoscopic submucous inferior turbinate resection(group A),26 cases by partial inferior turbinectomy(group B)and 30 cases by bipolar radiofrequency ablation(group C).The epithelium of the inferior turbinate of the every case in 3 groups was examined with histomorphology and ultrastructure techniques at 6 months after operation. The efficacy and the features of in the 3 groups were compared.The MTR was determined in the patients of the 3 groups.The histomorphology and ultrastructure of the inferior turbinate were observed at 6 months after operation.RESULTS All the cases with HR in 3 groups were followed up for 3 to 6 months after operation.Effective rates of group A,group B and group C were 100 %,100 % and 96.3 % respectively, while there was no significant difference among the three groups.Compared to the group B,surgical techniques applied in Group A and group C have more advantages because ultrastructure of inferior turbinate mucosal cilia and nasal mucociliary transport function were nearly normal at 3 to 6 months after operation. The advantages include operating easily,wound healing up fast.MTR between pre-and post-operation was significant difference in group B.Epithelial tissue remained intact in group A and group C,while epithelial tissue in group B was instead of fiber tissue at 6 months after operation.The ultrastructure of inferior turbinate mucosal cilia in group A and group C remained intact at 6 months after operation.CONCLUSION The transnasal endoscopic submucous inferior turbinate resection and bipolar radiofrequency ablation for treatment of chronic hypertrophy rhinitis are effective. Submucous minimally invasive surgery of the inferior turbinate deserves to be recommended.