Bioimpacts最新文献

{"title":"Vandetanib alters the tumoricidal capacity of human breast cancer stem cells via inhibiting vasculogenic capacity.","authors":"Sanya Haiaty,&nbsp;Mohammad-Reza Rashidi,&nbsp;Maryam Akbarzadeh,&nbsp;Ahad Bazmany,&nbsp;Mostafa Mostafazadeh,&nbsp;Saba Nikanfar,&nbsp;Roya Shabkhizan,&nbsp;Rostam Rezaeian,&nbsp;Reza Rahbarghazi,&nbsp;Mohammad Nouri","doi":"10.34172/bi.2022.24208","DOIUrl":"https://doi.org/10.34172/bi.2022.24208","url":null,"abstract":"<p><p></p><p><strong>Introduction: </strong>The inhibition of vascularization into tumor stroma as well as dynamic cell growth is the center of attention. Here, we aimed to examine the role of vandetanib on angiogenesis capacity of breast cancer stem cell (CSCs).</p><p><strong>Methods: </strong>MDA-MB-231 cells were exposed to different doses of vandetanib and survival rate was monitored. Stimulatory effects of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and epidermal growth factor (EGF) were evaluated in vandetanib-treated MDA-MB-231 cells. In vitro tubulogenesis capacity was studied on the Matrigel surface. The synergistic effects of vandetanib on cell survival were also assessed after PI3K and/or Wnt3a inhibition. Vascular endothelial (VE)-cadherin, matrix metalloproteinase-2 (MMP-2), -9, Wnt3a, and p-Akt/Akt ratio were measured using western blotting.</p><p><strong>Results: </strong>Vandetanib reduced survival rate in a dose-dependent manner (<i>P</i><0.05). Proliferative effects associated with VEGF, FGF, and EGF were blunted in these cells pre-exposed to vandetanib (<i>P</i><0.05). The microcirculation pattern's triple-negative breast cancer (TNBC) was suppressed by 1, 5 µM of vandetanib (<i>P</i><0.05). Hence 1, 5 µM of vandetanib potentially decreased the population of CD24^- cells. 1 and 5 µM of vandetanib inhibited cell proliferation by blocking PI3K and Wnt3a pathways and decreased the p-Akt/Akt ratio, Wnta3 protein levels (<i>P</i><0.05). 1 and 5 µM vandetanib combined with PI3K inhibitor diminished metastatic markers including, MMP-2, and MMP-9. The concurrent treatment (PI3K, inhibitor+ 1, 5 µM vandetanib) also considerably reduced epithelial-mesenchymal transition (EMT) markers such as VE-cadherin (<i>P</i><0.05).</p><p><strong>Conclusion: </strong>Vandetanib suppressed vasculogenic mimicry (VM) networking through blunting stemness properties, coincided with suppression of VE-cadherin in CSCs.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"13 5","pages":"405-413"},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8e/66/bi-13-405.PMC10509738.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41105134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative modeling of the mitral valve in normal and prolapse conditions.","authors":"Seyed Esmail Razavi,&nbsp;Amin Talebi","doi":"10.34172/bi.2023.24097","DOIUrl":"https://doi.org/10.34172/bi.2023.24097","url":null,"abstract":"<p><p></p><p><strong>Introduction: </strong>Computational modeling is one of the best non-invasive approaches to predicting the functional behavior of the mitral valve (MV) in health and disease. Mitral valve prolapse (MVP) due to partial or complete chordae tendineae rapture is the most common valvular disease and results in mitral regurgitation (MR).</p><p><strong>Methods: </strong>In this study, Image-based fluid-structure interaction (FSI) models of the human MV are developed in the normal physiological and posterior leaflet prolapse conditions. Detailed geometry of the healthy human MV is derived from Computed Tomography imaging data. To provide prolapse condition, some chords attached to the posterior leaflet are removed from the healthy valve. Both normal and prolapsed valves are embedded separately in a straight tubular blood volume and simulated under physiological systolic pressure loads. The Arbitrary Lagrangian-Eulerian finite element method is used to accommodate the deforming intersection boundaries of the blood and MV.</p><p><strong>Results: </strong>The stress values in the mitral components, and also flow patterns including the regurgitant flow rates are obtained and compared in both conditions through the simulation. These simulations have the potential to improve the treatment of patients with MVP, and also help surgeons to have more realistic insight into the dynamics of the MV in health and prolapse.</p><p><strong>Conclusion: </strong>In the prolapse model, computational results show incomplete leaflet coaptation, higher MR severity, and also a significant increment of posterior leaflet stress compared to the normal valve. Moreover, it is found more deviation of the regurgitant jet towards the left atrium wall due to the posterior leaflet prolapse.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"13 4","pages":"323-332"},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/53/01/bi-13-323.PMC10460767.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10117771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, characterization, and evaluation of pH-sensitive doxorubicin-loaded functionalized graphene oxide in osteosarcoma cells.","authors":"Forough Alemi,&nbsp;Masomeh Maleki,&nbsp;Mostafa Mir,&nbsp;Abbas Ebrahimi-Kalan,&nbsp;Mojtaba Zarei,&nbsp;Bahman Yousefi,&nbsp;Nadereh Rashtchizadeh","doi":"10.34172/bi.2022.23820","DOIUrl":"https://doi.org/10.34172/bi.2022.23820","url":null,"abstract":"<p><p></p><p><strong>Introduction: </strong>Doxorubicin (DOX) is one of the most common drugs in cancer treatment. However, its partial solubility along with the high incidence of side effects remains a challenge to tackle. To address these issues, we designed a formulation based on graphene oxide (GO) and used it as an anticancer drug delivery system.</p><p><strong>Methods: </strong>The physical and chemical properties of the formulation were studied using FTIR, SEM, EDX, Mapping, and XRD. Release studies in the <i>in vitro</i> condition were used to evaluate the pH sensitivity of drug release from nanocarriers. Other <i>in vitro</i> studies, including uptake assay, MTT, and apoptosis assay were carried out on the osteosarcoma cell line.</p><p><strong>Results: </strong><i>in vitro</i> release studies confirmed that the synthesized formulation provides a better payload release profile in acidic conditions, which is usually the case in the tumor site. On the OS cell line, the cytotoxicity of the DOX-loaded nanocarrier (IC50=0.293 μg/mL) and early apoptosis rate (33.80 % ) were higher in comparison to free DOX (IC50=0.472 μg/mL, and early apoptosis rate= 8.31 % ) after 48 hours.</p><p><strong>Conclusion: </strong>In summary, our results suggest a DOX-loaded graphene oxide carrier as a potential platform for targeting cancer cells.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"13 3","pages":"207-218"},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/db/87/bi-13-207.PMC10329751.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9816791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silibinin induces immunogenic cell death in cancer cells and enhances the induced immunogenicity by chemotherapy.","authors":"Sevda Jafari,&nbsp;Saba Heydarian,&nbsp;Raymond Lai,&nbsp;Elnaz Mehdizadeh Aghdam,&nbsp;Ommoleila Molavi","doi":"10.34172/bi.2022.23698","DOIUrl":"https://doi.org/10.34172/bi.2022.23698","url":null,"abstract":"<p><p><i><b>Introduction:</b> </i> Silibinin is a natural flavonoid compound known to induce apoptosis in cancer cells. Despite silibinin's safety and efficacy as an anticancer drug, its effects on inducing immunogenic cell death (ICD) are largely unknown. Herein, we have evaluated the stimulating effects of silibinin on ICD in cancer cells treated with silibinin alone or in combination with chemotherapy. <i><b>Methods:</b> </i> The anticancer effect of silibinin, alone or in combination with doxorubicin or oxaliplatin (OXP), was assessed using the MTT assay. Compusyn software was used to analyze the combination therapy data. Western blotting was conducted to examine the level of STAT3 activity. Flow cytometry was used to analyze calreticulin (CRT) and apoptosis. The heat shock protein (HSP70), high mobility group box protein1 (HMGB1), and IL-12 levels were assessed by ELISA. <i><b>Results:</b> </i> Compared to the negative control groups, silibinin induced ICD in CT26 and B16F10 cells and significantly enhanced the induction of this type of cell death by doxorubicin, and these changes were allied with substantial increases in the level of damage-associated molecular patterns (DAMPs) including CRT, HSP70, and HMGB1. Furthermore, conditioned media from cancer cells exposed to silibinin and doxorubicin was found to stimulate IL-12 secretion in dendritic cells (DCs), suggesting the link of this treatment with the induction of Th1 response. Silibinin did not augment the ICD response induced by OXP. <i><b>Conclusion:</b> </i> Our findings showed that silibinin can induce ICD and it potentiates the induction of this type of cell death induced by chemotherapy in cancer cells.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"13 1","pages":"51-61"},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d5/b0/bi-13-51.PMC9923812.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10767203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autophagy induced macrophages by α-alumina(α-AL2O3) conjugated cysteine peptidase, enhances the cytotoxic activity of CD8⁺ T lymphocytes against <i>Leishmania major</i>.","authors":"Fatemeh Beyzay,&nbsp;Ahmad Zavaran Hosseini,&nbsp;Ali Hazrati,&nbsp;Mozhdeh Karimi,&nbsp;Sara Soudi","doi":"10.34172/bi.2023.25282","DOIUrl":"https://doi.org/10.34172/bi.2023.25282","url":null,"abstract":"<p><p></p><p><strong>Introduction: </strong>Induction of a protective immune response against <i>Leishmania major</i> requires the activation of both TH1 and CD8⁺ T lymphocytes. Because <i>L. major</i> is an intra-phagosomal parasite, its antigens do not have access to MHC-I. The present study aimed to evaluate the effect of cysteine peptidase A (CPA)/cysteine peptidase B (CPB) conjugated to α-AL2O3 on autophagy induction in <i>L. major</i> infected macrophages and subsequent activation of cytotoxic CD8⁺ T lymphocytes.</p><p><strong>Methods: </strong>Recombinant CPA and CPB of <i>L. major</i> were produced in expression vectors and purified. Aldehyde functionalized α-AL2O3 were conjugated to hydrazine-modified CPA/CPB by a chemical bond was confirmed by Fourier-transform infrared spectroscopy (FTIR). The High efficient internalization of α-AL2O3 conjugated CPA/CPB to macrophages was confirmed using a fluorescence microscope and flowcytometry. Induction of the acidic autophagosome and LC3 conversion in macrophages was determined by acridine orange (AO) staining and western blot. Autophagy-activated macrophages were used for CD8⁺ T cell priming. Cytotoxic activity of the primed CD8⁺ T cell against <i>L. major</i> infected macrophages was measured using apoptosis assay.</p><p><strong>Results: </strong>α-AL2O3 conjugated CPA/CPB enhances macrophages antigen uptake and increases acidic vacuole formation and LC-3I to LC-3II conversion. Co-culture of autophagy-activated macrophages with CD8⁺ T cells augmented CD8⁺ T cells priming and proliferation more than in other study groups. These primed CD8⁺ T cells induce significant apoptotic death of <i>L. major</i> infected macrophages compared with non-primed CD8⁺ T cells.</p><p><strong>Conclusion: </strong>α-AL2O3 nanoparticles enhance the cross-presentation of <i>L. major</i> antigens to CD8⁺ T cells by inducing autophagy. This finding supports the positive role of autophagy and encourages the use of α-AL2O3 in vaccine design.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"13 5","pages":"393-403"},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cd/8b/bi-13-393.PMC10509742.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41116216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetics of the blood pressure reactivity to salt: Is the salt sensitive phenotype correctable?","authors":"Luigi X Cubeddu","doi":"10.34172/bi.2023.27552","DOIUrl":"https://doi.org/10.34172/bi.2023.27552","url":null,"abstract":"<p><p>Salt sensitivity defines a state characterized by a highly reactive blood pressure to changes in salt intake. The salt-sensitive phenotype is strongly associated with hypertension, visceral adiposity/metabolic syndrome, and ageing. Obesity accounts for around 70% of hypertension in young adults, and 30% to 50% of adult hypertensives carry the salt-sensitive phenotype. It is estimated that the salt-sensitive phenotype is responsible for high blood pressure in over 600 million adults. But is the salt-sensitive phenotype correctable? Interventional, controlled, clinical trials in obese adolescents and young obese adults, demonstrated that weight-reducing lifestyle modifications revert the salt-sensitive to the salt-resistant phenotype, and restored the faulty production of nitric oxide. Correction of the salt-sensitive phenotype lowers the blood pressure by reducing its reactivity to dietary salt. In a random sample of obese adults subjected to lifestyle modifications, those who were salt-resistant at baseline, were also normotensive and failed to further lower their blood pressure despite a 12% drop in body weight. The salt-resistant phenotype protects the metabolically healthy obese from hypertension, even if their salt consumption is comparable to that of salt-sensitive obese. In summary, at early stages, the elevated blood pressure of obesity, is determined by epigenetic changes leading to a state of salt-sensitivity.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"13 5","pages":"355-358"},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/bb/b9/bi-13-355.PMC10509743.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41180308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibitory effects of mixed flavonoid supplements on unraveled DSS-induced ulcerative colitis and arthritis.","authors":"Siva Prasad Panda,&nbsp;Mahamat Sami Adam Mahamat,&nbsp;Malikyahia Abdul Rasool,&nbsp;Dsnbk Prasanth,&nbsp;Idris Adam Ismail,&nbsp;Moyed Abasher Ahmed Abasher,&nbsp;Bikash Ranjan Jena","doi":"10.34172/bi.2022.23523","DOIUrl":"https://doi.org/10.34172/bi.2022.23523","url":null,"abstract":"<p><p><i><b>Introduction:</b> </i> The mixed flavonoid supplement (MFS) [Trimethoxy Flavones (TMF) + epigallocatechin-3-gallate (EGCG)] can be used to suppress inflammatory ulcers as an ethical medicine in Ayurveda. The inflammation of the rectum and anal regions is mostly attributed to nuclear factor kappa beta (NF-κB) signaling. NF-κB stimulates the expression of matrix metalloproteinase (MMP9), inflammatory cytokines tumor necrosis factor (TNF-α), and interleukin-1β (IL-1β). Although much research targeted the NF-κB and MMP9 signaling pathways, a subsequent investigation of target mediators in the inflammatory ulcer healing and NF-κB pathway has not been done. <i><b>Methods:</b> </i> The docking studies of compounds TMF and EGCG were performed by applying PyRx and available software to understand ligand binding properties with the target proteins. The synergistic ulcer healing and anti-arthritic effects of MFS were elucidated using dextran sulfate sodium (DSS)-induced colon ulcer in Swiss albino rats. The colon mucosal injury was analyzed by colon ulcer index (CUI) and anorectic tissue microscopy. The IL-1β, tumor necrosis factor (TNF-α), and the pERK, MMP9, and NF-κB expressions in the colon tissue were determined by ELISA and Western blotting. RT-PCR determined the mRNA expression for inflammatory marker enzymes. <i><b>Results:</b> </i> The docking studies revealed that EGCG and TMF had a good binding affinity with MMP9 (i.e., -6.8 and -6.0 Kcal/mol) and NF-kB (-9.4 and 8.3 kcal/mol). The high dose MFS better suppressed ulcerative colitis (UC) and associated arthritis with marked low-density pERK, MMP9, and NF-κB proteins. The CUI score and inflammatory mediator levels were suppressed with endogenous antioxidant levels in MFS treated rats. <i><b>Conclusion:</b> </i> The MFS effectively unraveled anorectic tissue inflammation and associated arthritis by suppressing NF-κB-mediated MMP9 and cytokines.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"13 1","pages":"73-84"},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/38/34/bi-13-73.PMC9923810.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10767206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SARS-CoV-2 vaccine-triggered autoimmunity: Molecular mimicry and/or bystander activation of the immune system.","authors":"Azam Safary,&nbsp;Mostafa Akbarzadeh-Khiavi,&nbsp;Jaleh Barar,&nbsp;Yadollah Omidi","doi":"10.34172/bi.2023.27494","DOIUrl":"https://doi.org/10.34172/bi.2023.27494","url":null,"abstract":"<p><p>Induced autoimmunity or autoinflammatory-like conditions as a rare vaccine-related adverse event have been reported following COVID-19 vaccination. Such inadvertent adverse reactions have raised somewhat concerns about the long-term safety of the developed vaccines. Such multifactorial phenomena may be related to the cross-reactivity between the viral-specific antigens with the host self-proteins through molecular mimicry mechanism and/or nonspecific bystander activation of the non-target antigen-independent immunity by the entities of the vaccine products. However, due to the low incidence of the reported/identified individuals and insufficient evidence, autoimmunity following the COVID-19 vaccination has not been approved. Thereby, it seems that further designated studies might warrant post-monitoring of the inevitable adverse immunologic reactions in the vaccinated individuals, especially among hypersensitive cases, to address possible immunological mechanisms induced by the viral vaccines, incorporated adjuvants, and even vaccine delivery systems.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"13 4","pages":"269-273"},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b2/ef/bi-13-269.PMC10460773.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10122602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differentiation and molecular characterization of endothelial progenitor and vascular smooth muscle cells from induced pluripotent stem cells.","authors":"Mohammadreza Dastouri,&nbsp;Hilal Ozdag,&nbsp;Ahmet Ruchan Akar,&nbsp;Alp Can","doi":"10.34172/bi.2022.24132","DOIUrl":"https://doi.org/10.34172/bi.2022.24132","url":null,"abstract":"<p><p></p><p><strong>Introduction: </strong>Pluripotent stem cells have been used by various researchers to differentiate and characterize endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) for the clinical treatment of vascular injuries. Studies continue to differentiate and characterize the cells with higher vascularization potential and low risk of malignant transformation to the recipient. Unlike previous studies, this research aimed to differentiate induced pluripotent stem (iPS) cells into endothelial progenitor cells (EPCs) and VSMCs using a step-wise technique. This was achieved by elucidating the spatio-temporal expressions of the stage-specific genes and proteins during the differentiation process. The presence of highly expressed oncogenes in iPS cells was also investigated during the differentiation period.</p><p><strong>Methods: </strong>Induced PS cells were differentiated into lateral mesoderm cells (Flk1⁺). The Flk1⁺ populations were isolated on day 5.5 of the mesodermal differentiation period. Flk1⁺ cells were further differentiated into EPCs and VSMCs using VEGF₁₆₅ and platelet-derived growth factor-BB (PDGF-BB), respectively, and then characterized using gene expression levels, immunocytochemistry (ICC), and western blot (WB) methods. During the differentiation steps, the expression levels of the marker genes and proto-oncogenic <i>Myc</i> and <i>Klf4</i> genes were simultaneously studied.</p><p><strong>Results: </strong>The optimal time for the isolation of Flk1⁺ cells was on day 5.5. EPCs and VSMCs were differentiated from Flk1⁺ cells and characterized with EPC-specific markers, including <i>Kdr, Pecam1, CD133, Cdh5, Efnb2, Vcam1</i>; and VSMC-specific markers, including <i>Acta2, Cnn1, Des,</i> and <i>Myh11</i>. Differentiated cells were validated based on their temporal gene expressions, protein synthesis, and localization at certain time points. Significant decreases in <i>Myc</i> and <i>Klf4</i> gene expression levels were observed during the EPCs and VSMC differentiation period.</p><p><strong>Conclusion: </strong>EPCs and VSMCs were successfully differentiated from iPS cells and characterized by gene expression levels, ICC, and WB. We observed significant decreases in oncogene expression levels in the differentiated EPCs and VSMCs. In terms of safety, the described methodology provided a better safety margin. EPCs and VSMC obtained using this method may be good candidates for transplantation and vascular regeneration.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"13 4","pages":"289-300"},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ae/cd/bi-13-289.PMC10460769.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10475371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytotoxicity of WT1-reactive T cells against Wilms tumor: An implication for antigen-specific adoptive immunotherapy.","authors":"Seyed Mostafa Monzavi,&nbsp;Amir Ali Hamidieh,&nbsp;Mohammad Vasei,&nbsp;Jafar Ai,&nbsp;Naser Ahmadbeigi,&nbsp;Hamid Arshadi,&nbsp;Samad Muhammadnejad,&nbsp;Abdol-Mohammad Kajbafzadeh","doi":"10.34172/bi.2023.27576","DOIUrl":"https://doi.org/10.34172/bi.2023.27576","url":null,"abstract":"Introduction: T cells that recognize WT1 peptides have been shown to efficiently eliminate WT1-expressing tumor cells. This study was designed to investigate the feasibility of isolating WT1-reactive T cells from peripheral blood mononuclear cells (PBMCs) from healthy donors and patients with Wilms tumor, and to assess the cytotoxicity mediated by these cells against Wilms tumor cells (WiTu cells). Methods: WT1-reactive T cells were enriched and isolated by stimulating PBMCs with a WT1 peptide pool and interferon-γ capture-based immunomagnetic separation (IMS). Using the lactate dehydrogenase release assay, the in vitro cytotoxicity of the isolated cells and standard chemotherapy was evaluated on WiTu cells. Results: Higher proportions of WT1-reactive T cells were isolated from patients with Wilms tumor compared to those isolated from HDs. WT1-reactive T cells produced > 50% specific lysis when co-cultured with WT1+ WiTu cells at the highest effector-to-target (E:T) ratio in this study (i.e., 5:1), compared to <23% when co-cultured with WT1- WiTu cells at the same ratio. WT1-reactive T cells showed anti-tumoral activity in a dose-dependent manner and mediated significantly greater cytotoxicity than the non-WT1-reactive fraction of PBMCs on WT1+ WiTu cells. The cytotoxicity of standard chemotherapy was significantly lower than that of WT1-reactive T cells when co-cultured with WT1+ WiTu cells at E:T ratios of 2:1 and 5:1. Conclusion: WT1-reactive T cells can be effectively enriched from the PBMCs of patients with Wilms tumor. Ex vivo generated WT1-reactive T cells might be considered an adoptive immunotherapeutic option for WT1+ Wilms tumors.","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"13 5","pages":"415-424"},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f0/b0/bi-13-415.PMC10509739.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41161023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}