Dynamic analysis of cancer-immune system with Allee effect

There are numbers of mathematical models to describe the relation between immune effector cells and cancer cells. The purpose of this thesis is to explore the influence of Allee effect on immune effector cells and cancer cells. First, we introduce some background information of how the immune system inhibit and suppress cancer growth and Allee effect. In Chapter 2, we propose a general model to describe the interaction between immune effector cells and cancers. We discuss some basic dynamical properties of the system under strong Allee effect and weak Allee effect with linear functional responses. For instance, the existence of equilibrium points and their local stabilities. In Chapter 3, using Matlab code, we do sampling-based sensitive analysis on the density of cancer cells. Sensitive analysis can narrow down the parameter of interest and suggest the most significant parameter that affect the density of cancer cells. In Chapter 4, due to the difficulty of solving the explicit form of positive equilibrium point. We give numerical simulation to explore the existence of positive equilibrium points and their stabilities. At last, in Chapter 5, we summarize the results in this thesis, and indicate some problems for future work

Doxorubicin resistance in breast cancer xenografts and cell lines can be counterweighted by microRNA-140-3p, through PD-L1 suppression

Background. Doxorubicin, a first-line chemotherapeutic drug for breast cancer, kills cancer cells by inducing DNA-crosslinking damage. Dysregulated micro-RNA (miRNA) is associated with the drug resistance of tumors. However, little is known about the effect of miRNA-140-3p on DOX resistance of breast cancer. Methods. The miRNA microarray was used to sequence the transcripts of DOX-chemoresistant breast cancer tissues and DOX-chemosensitive tissues. Then, the breast cancer tissue chip in the GEO database was also analyzed to screen the target gene. Flow cytometry, in situ hybridisation (ISH), immunohistochemistry (IHC), Western blot, cell proliferation assay, real-time PCR analyses (qRT-PCR), and pull-down assay were used to explore the effects of miRNA-140-3p and programmed death ligand-1 (PD-L1) on the chemoresistance of DOX-resistant breast cancer cells treated with DOX. In vivo, the DOX-resistant breast cancer cell lines treated with miRNA-140-3p overexpression were injected subcutaneously into mice to construct breast cancer subcutaneous xenograft tumor models. Results. Based on miRNA microarray, GEO database, and bioinformatics analysis, it was found that miRNA-140-3p and PD-L1 are the core molecules in the DOX resistance regulatory network in breast cancer, and lower miRNA-140-3p and higher PD-L1 expression levels were observed in DOX-resistant breast cancer tissues and cells. IHC results showed that compared with breast cancer tissues with high miRNA-140-3p expression, PD-L1 protein expression levels in breast cancer tissues with low miRNA-140-3p were significantly higher (P<0.01). Moreover, compared with DOX-sensitive tissues, the levels of PD-L1 protein expression in DOX-resistant tissues were significantly higher (P<0.01). In in vitro and in vivo experiments, the introduction of miRNA-140-3p decreased PD-L1 expression. Mechanically, we found that the MCF7/DOX and HS598T/DOX cells pretreated with miRNA140-3p inhibitor or exosomes containing PD-L1 have higher stemness and lower apoptosis rate, which can be abrogated by co-treating cells with anti-PD-L1 antibody or miRNA-140-3p mimic. Conclusions. MiRNA-140-3p can suppress PD-L1 expression in breast cancer cell-derived exosomes, thereby attenuating the chemoresistance induced by DOX in breast cancer

Imobilizacija tirozinaze na pustu od ugljičnih vlakana s (3-aminopropil)trietoksisilanom za protočnu elektrokemijsku detekciju fenolnih spojeva

Tyrosinase (TYR) was covalently immobilized onto amino-functionalized carbon felt (CF) surface via glutaraldehyde (GA). Prior to the TYR-immobilization, primary amino group was introduced to the CF surface by treatment with 3-aminopropyltriethoxysilane (APTES). The resulting TYR-immobilized CF was used as a working electrode unit of an electrochemical flow-through detector for mono- and di-phenolic compounds (i.e., catechol, p-cresol, phenol and p-chlorophenol). Additionally, flow injection peaks based on electroreduction of the enzymatically produced o-quinone species were detected at −0.05 V vs. Ag/AgCl. The resulting TYR/GA/APTES/CF biosensor responded well to all compounds tested with limits of detection range from 7.5 to 35 nmol l–1 (based on three times S/N ratio). Moreover, such modified electrode exhibits good stability and reproducibility for catechol. No serious degradation of the peak current was found over 30 consecutive injections. This work is licensed under a Creative Commons Attribution 4.0 International License.Tirozinaza (TYR) je kovalentno vezana na aminiranu površinu pusta izrađenog od ugljičnih vlakana (CF) s pomoću glutaraldehida (GA). Prije imobilizacije tirozinaze primarna amino-skupina uvedena je na ugljična vlakna (3-aminopropil)trietoksisilanom (APTES). CF s imobiliziranom tirozinazom upotrijebljen je kao elektroda u protočnom elektrokemijskom detektoru jednostruko i dvostruko hidroksiliranih fenola (katehol, p-krezol, fenol, p-klorfenol). Pri − 0,05 V (u odnosu na Ag/AgCl) uočeni su protočni injekcijski signali elektroredukcije o-kinona nastalog enzimskom reakcijom. Biosenzor TYR/GA/APTES/CF dobro se odaziva za sve ispitane spojeve uz detekcijski limit od 7,5 do 35 nmol l–1 (tri puta veći signal od šuma). Modificirana elektroda stabilna je i pokazuje dobru reproducibilnost za katehol. Jakost struje signala nije se značajno smanjila ni nakon 30 uzastopnih injektiranja. Ovo djelo je dano na korištenje pod licencom Creative Commons Imenovanje 4.0 međunarodna

Apoptosis of supraoptic AVP neurons is involved in the development of central diabetes insipidus after hypophysectomy in rats

<p>Abstract</p> <p>Background</p> <p>It has been reported that various types of axonal injury of hypothalamo-neurohypophyseal tract can result in degeneration of the magnocellular neurons (MCNs) in hypothalamus and development of central diabetes insipidus (CDI). However, the mechanism of the degeneration and death of MCNs after hypophysectomy in vivo is still unclear. This present study was aimed to disclose it and to figure out the dynamic change of central diabetes insipidus after hypophysectomy.</p> <p>Results</p> <p>The analysis on the dynamic change of daily water consumption (DWC), daily urine volume(DUV), specific gravity of urine(USG) and plasma vasopressin concentration showed that the change pattern of them was triphasic and neuron counting showed that the degeneration of vasopressin neurons began at 10 d, aggravated at 20 d and then stabilized at 30 d after hypophysectomy. There was marked upregulation of cleaved Caspase-3 expression of vasopressin neurons in hypophysectomy rats. A "ladder" pattern of migration of DNA internucleosomal fragments was detected and apoptotic ultrastructure was found in these neurons. There was time correlation among the occurrence of diabetes insipidus, the changes of plasma vasopressin concentration and the degeneration of vasopressin neurons after hypophysectomy.</p> <p>Conclusion</p> <p>This study firstly demonstrated that apoptosis was involved in degeneration of supraoptic vasopressin neurons after hypophysectomy in vivo and development of CDI. Our study on time course and correlations among water metabolism, degeneration and apoptosis of vasopressin neurons suggested that there should be an efficient therapeutic window in which irreversible CDI might be prevented by anti-apoptosis.</p

MicroRNA-200c overexpression inhibits tumorigenicity and metastasis of CD117+CD44+ ovarian cancer stem cells by regulating epithelial-mesenchymal transition

BACKGROUND: Cancer stem cells (CSCs) are believed to be ‘seed cell’ in cancer recurrence and metastasis. MicroRNAs (miRNAs) can play an important role in the progression of primary tumor towards metastasis by regulating the epithelial-mesenchymal transition (EMT). The goal of this study was to investigate the effect of miRNA-200c overexpression on the EMT, tumorigenicity and metastasis of epithelial ovarian cancer (EOC) CSCs. METHODS: The EOC CD117(+)CD44(+)CSCs were isolated from the human ovarian cancer cell line SKOV3 by using a magnetic-activated cell sorting system, and the lentivirus miR-200c transduced CSCs were then selected for the study. The assays of colony forming, wound healing, cellular migration in vitro and tumor progression in vivo were performed. RESULTS: The miR-200c expression was reduced in the CD117(+)CD44(+)CSCs compared with the non-CD117(+)CD44(+)CSCs. However, the stable overexpression of the miR-200c in the CD117(+)CD44(+)CSCs resulted in a significant down-regulation of ZEB-1 and the Vimentin expression, an upregulation of the E-cadherin expression as well as a decrease of colony forming, migratory and invasion in vitro. Importantly, the miR-200c overexpression significantly inhibited the CD117(+)CD44(+)CSCs xenograft growth and lung metastasis in vivo in nude mice by inhibition of the EMT. In addition, the down-regulation of ZEB-1 showed the same efficacy as the miR-200c overexpression in the CD117(+)CD44(+)CSCs. CONCLUSION: These findings from this study suggest that the miR-200c overexpression may be considered a critical approach for the EOC CD117(+)CD44(+)CSCs in clinical trials

Proteasome activator 28A: A clinical biomarker and pharmaceutical target in acute cerebral infarction therapy

Purpose: To determine the dynamic changes in serum levels of PA28α in patients with acute cerebral infarction (ACI), and to investigate its correlation with infarct size and neurological deficit of the disease. Methods: A total of 100 ACI patients and 100 healthy volunteers were recruited from The First Affiliated Hospital of Xinxiang Medical University as case and control groups, respectively. Their serum levels of PA28α were determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The potential of PA28α in predicting the incidence of ACI was assessed by plotting ROC curves. Multivariate logistic regression analysis was conducted to investigate the risk factors of ACI. In addition, an ACI model in rats was established, and ACI rats were classified into 1, 3, 5, 7 and 14 day subgroups based on the duration post-ACI. Rats in the sham group served as control. Results: Serum level of PA28α was significantly higher in ACI patients than in controls. Moreover, the serum level of PA28α at admission was positively correlated to the NIHSS score and infarct volume of ACI patients. The level of PA28α in ACI rats gradually increased post-ACI, reaching a peak on day 7. The number of apoptotic brain cells in ACI rats gradually decreased after ACI. In addition, PA28α level was negatively correlated to the number of apoptotic brain cells in ACI rats (R2 = 0.5148, p &lt; 0.001). Conclusion: The serum level of PA28α is elevated in ACI patients, and is positively correlated to infarct volume and neurological deficit of the disease. The dynamic change in brain cell apoptosis post-ACI is negatively correlated to the serum level of PA28α. These findings may provide theoretical basis for the diagnosis and treatment of ACI