Cellular and molecular bioengineering最新文献

{"title":"TNF-α Preconditioning Promotes a Proangiogenic Phenotype in hiPSC-Derived Vascular Smooth Muscle Cells.","authors":"Daniel C Sasson, Sara Islam, Kaiti Duan, Biraja C Dash, Henry C Hsia","doi":"10.1007/s12195-023-00764-0","DOIUrl":"10.1007/s12195-023-00764-0","url":null,"abstract":"<p><strong>Introduction: </strong>hiPSC-VSMCs have been suggested as therapeutic agents for wound healing and revascularization through the secretion of proangiogenic factors. However, methods of increasing cell paracrine secretion and survivability have thus far yielded inconsistent results. This study investigates the effect of pre-conditioning of hiPSC-VSMCs with TNF-α and their integration into 3D collagen scaffolds on cellular viability and secretome.</p><p><strong>Methods: </strong>hiPSC-VSMCs were dual-plated in a 2D environment. TNF-α was introduced to one plate. Following incubation, cells from each plate were divided and added to type-I collagen scaffolds. TNF-α was introduced to two sets of scaffolds, one from each 2D plate. Following incubation, scaffolds were harvested for their media, tested for cell survivability, cytotoxicity, and imaged. Intra-media VEGF and bFGF levels were evaluated using ELISA testing.</p><p><strong>Results: </strong>hiPSC-VSMCs exposed to TNF-α during collagen scaffold proliferation and preconditioning showed an increase in cell viability and less cytotoxicity compared to non-exposed cells and solely-preconditioned cells. Significant increases in bFGF expression were found in pre-conditioned cell groups with further increases found in cells subsequently exposed during intra-scaffold conditioning. A significant increase in VEGF expression was found in cell groups exposed during both pre-conditioning and intra-scaffold conditioning. Fibroblasts treated with any conditioned media demonstrated increased migration potential.</p><p><strong>Conclusions: </strong>Conditioning hiPSC-VSMCs embedded in scaffolds with TNF-α improves cellular viability and increases the secretion of paracrine factors necessary for wound healing mechanisms such as migration.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s12195-023-00764-0.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"16 3","pages":"231-240"},"PeriodicalIF":2.8,"publicationDate":"2023-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10338418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9828432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Can Bard, Google's Experimental Chatbot Based on the LaMDA Large Language Model, Help to Analyze the Gender and Racial Diversity of Authors in Your Cited Scientific References?","authors":"Michael R King","doi":"10.1007/s12195-023-00761-3","DOIUrl":"10.1007/s12195-023-00761-3","url":null,"abstract":"<p><p>There is a growing recognition that scientific articles featuring women and people of color as first and last (senior) author are undercited in the literature relative to male and non-minority race authors. Some limited tools now exist to analyze the diversity of manuscript bibliographies, with acknowledged limitations. Recently the journal editors and publications chair of the Biomedical Engineering Society have recommended that authors include an optional \"Citation Diversity Statement\" in their articles, however adoption of this practice has, to date, been slow. Inspired by the current excitement and enthusiasm for artificial intelligence (AI) large language model chatbots, I sought to determine whether Google's new Bard chatbot could be used to assist authors in this process. It was determined that the Bard technology is not yet up to this task, however, by showing some modest improvement in the fidelity of references, combined with the not-yet realized live search capabilities, the author is nevertheless optimistic that this technology can one day be utilized for this purpose as it continues to improve.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"16 2","pages":"175-179"},"PeriodicalIF":2.8,"publicationDate":"2023-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10121931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9447378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circ_0004585 Facilitates Tumorigenesis of Colorectal Cancer <i>Via</i> Modulating the miR-338-3p/ZFX Axis and Activating the MEK/ERK Pathway.","authors":"Zenghai Lin,&nbsp;Jianwei Lin","doi":"10.1007/s12195-022-00756-6","DOIUrl":"https://doi.org/10.1007/s12195-022-00756-6","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is a common malignant tumor in the digestive tract. Circular RNAs (circRNAs) have been identified as crucial regulators of tumorigenesis. However, the role and potential mechanism of circ_0004585 in CRC are poorly understood.</p><p><strong>Methods: </strong>The expression of circ_0004585, microRNA-338-3p (miR-338-3p), and zinc finger protein X-linked (ZFX) was detected by quantitative real-time PCR and Western blot. Cell proliferation, cell cycle arrest, apoptosis, and angiogenesis were evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), 5-Ethynyl-2'-deoxyuridine (EdU), flow cytometry and tube formation assays. Western blot assay was applied to detect the expression of epithelial-mesenchymal transition (EMT)-related proteins and MEK/ERK signaling pathway-related proteins. A xenograft model was used to analyze tumor growth <i>in vivo</i>. The targeted relationship between miR-338-3p and circ_0004585/ZFX was verified by a dual-luciferase reporter assay.</p><p><strong>Results: </strong>Circ_0004585 and ZFX were up-regulated, while miR-338-3p was down-regulated in CRC tissues and cells. Silencing of circ_0004585 inhibited proliferation, angiogenesis, and EMT and triggered apoptosis in CRC cells. Consistently, circ_0004585 depletion blocked tumor growth <i>in vivo</i>. Circ_0004585 contributed to CRC cell development <i>via</i> sequestering miR-338-3p. Also, miR-338-3p hindered the malignant progression of CRC cells by targeting ZFX. Circ_0004585 activated MEK/ERK pathway <i>via</i> regulating ZFX.</p><p><strong>Conclusion: </strong>Circ_0004585 facilitated CRC progression through modulating miR-338-3p/ZFX/MEK/ERK pathway, which might provide a potential therapeutic target for CRC.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s12195-022-00756-6.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"16 2","pages":"159-171"},"PeriodicalIF":2.8,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10121944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9447377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Integrative Biology Approach to Quantify the Biodistribution of Azidohomoalanine <i>In Vivo</i>.","authors":"Aya M Saleh, Tyler G VanDyk, Kathryn R Jacobson, Shaheryar A Khan, Sarah Calve, Tamara L Kinzer-Ursem","doi":"10.1007/s12195-023-00760-4","DOIUrl":"10.1007/s12195-023-00760-4","url":null,"abstract":"<p><strong>Background: </strong>Identification and quantitation of newly synthesized proteins (NSPs) are critical to understanding protein dynamics in development and disease. Probing the nascent proteome can be achieved using non-canonical amino acids (ncAAs) to selectively label the NSPs utilizing endogenous translation machinery, which can then be quantitated with mass spectrometry. We have previously demonstrated that labeling the <i>in vivo</i> murine proteome is feasible via injection of azidohomoalanine (Aha), an ncAA and methionine (Met) analog, without the need for Met depletion. Aha labeling can address biological questions wherein temporal protein dynamics are significant. However, accessing this temporal resolution requires a more complete understanding of Aha distribution kinetics in tissues.</p><p><strong>Results: </strong>To address these gaps, we created a deterministic, compartmental model of the kinetic transport and incorporation of Aha in mice. Model results demonstrate the ability to predict Aha distribution and protein labeling in a variety of tissues and dosing paradigms. To establish the suitability of the method for <i>in vivo</i> studies, we investigated the impact of Aha administration on normal physiology by analyzing plasma and liver metabolomes following various Aha dosing regimens. We show that Aha administration induces minimal metabolic alterations in mice.</p><p><strong>Conclusions: </strong>Our results demonstrate that we can reproducibly predict protein labeling and that the administration of this analog does not significantly alter <i>in vivo</i> physiology over the course of our experimental study. We expect this model to be a useful tool to guide future experiments utilizing this technique to study proteomic responses to stimuli.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s12195-023-00760-4.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"16 2","pages":"99-115"},"PeriodicalIF":2.8,"publicationDate":"2023-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10121978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9744139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial Intelligence, Chatbots, Plagiarism and Basic Honesty: Comment.","authors":"Amnuay Kleebayoon, Viroj Wiwanitkit","doi":"10.1007/s12195-023-00759-x","DOIUrl":"10.1007/s12195-023-00759-x","url":null,"abstract":"","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"16 2","pages":"173-174"},"PeriodicalIF":2.8,"publicationDate":"2023-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10121937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9447376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor-Targeting Extracellular Vesicles Loaded with siS100A4 for Suppressing Postoperative Breast Cancer Metastasis.","authors":"Ruiling Pan, Tiancheng He, Kun Zhang, Lewei Zhu, Jiawei Lin, Peixian Chen, Xiangwei Liu, Huiqi Huang, Dan Zhou, Wei Li, Shuqing Yang, Guolin Ye","doi":"10.1007/s12195-022-00757-5","DOIUrl":"10.1007/s12195-022-00757-5","url":null,"abstract":"<p><strong>Introduction: </strong>S100A4 promotes the establishment of tumor microenvironment for malignant cancer cells, and knockdown of S100A4 can inhibit tumorigenesis. However, there is no efficient way to target S100A4 in metastatic tumor tissues. Here, we investigated the role of siS100A4-loaded iRGD-modified extracellular vesicles (siS100A4-iRGD-EVs) in postoperative breast cancer metastasis.</p><p><strong>Methods: </strong>siS100A4-iRGD-EVs nanoparticles were engineered and analyzed using TEM and DLS. siRNA protection, cellular uptake, and cytotoxicity of EV nanoparticles were examined <i>in vitro</i>. Postoperative lung metastasis mouse model was created to investigate the tissue distribution and anti-metastasis roles of nanoparticles <i>in vivo</i>.</p><p><strong>Results: </strong>siS100A4-iRGD-EVs protected siRNA from RNase degradation, enhanced the cellular uptake and compatibility <i>in vitro</i>. Strikingly, iRGD-modified EVs significantly increased tumor organotropism and siRNA accumulation in lung PMNs compared to siS100A4-EVs <i>in vivo</i>. Moreover, siS100A4-iRGD-EVs treatment remarkedly attenuated lung metastases from breast cancer and increased survival rate of mice through suppressing S100A4 expression in lung.</p><p><strong>Conclusions: </strong>siS100A4-iRGD-EVs nanoparticles show more potent anti-metastasis effect in postoperative breast cancer metastasis mouse model.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s12195-022-00757-5.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"16 2","pages":"117-125"},"PeriodicalIF":2.8,"publicationDate":"2023-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10121989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9744142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of the Therapeutic Effects of Palbociclib Conjugated Magnetic Nanoparticles on Different Types of Breast Cancer Cell Lines.","authors":"Maryam Parsian, Pelin Mutlu, Negar Taghavi Pourianazar, Serap Yalcin Azarkan, Ufuk Gunduz","doi":"10.1007/s12195-022-00758-4","DOIUrl":"10.1007/s12195-022-00758-4","url":null,"abstract":"<p><strong>Introduction: </strong>Drug targeting and controlled drug release systems in cancer treatment have many advantages over conventional chemotherapy in terms of limiting systemic toxicity, side effects, and overcoming drug resistance.</p><p><strong>Methods and results: </strong>In this paper, fabricating nanoscale delivery system composed of magnetic nanoparticles (MNPs) covered with poly-amidoamine (PAMAM) dendrimers and using its advantages were fully used to help the chemotherapeutic drug, Palbociclib, effectively reach tumors, specifically and stay stable in the circulation longer. In order to determine whether conjugate selectivity can be increased for the specific drug type, we have reported different strategies for loading and conjugation of Palbociclib to different generations of magnetic PAMAM dendrimers. The best method leading to the highest amount of Palbociclib conjugation was chosen, and the characterization of the Palbociclib conjugated dendrimeric magnetic nanoparticles (PAL-DcMNPs) were performed. <i>In vitro</i> pharmacological activity of the conjugation was demonstrated by measuring the cell viability and lactate dehydrogenase (LHD) release. Obtained results indicated that PAL-DcMNPs treatment of the breast cancer cell lines, leads to an increase in cell toxicity compared to free Palbociclib. The observed effects were more evident for MCF-7 cells than for MDA-MB231 and SKBR3 cells, considering that viability decreased to 30% at 2.5 <i>µ</i>M treatment of PAL-DcMNPs at MCF-7 cells. Finally, in Palbociclib and PAL-DcMNPs treated breast cancer cells, the expression levels of some pro-apoptotic and drug resistance related genes were performed by RT-PCR analysis.</p><p><strong>Conclusion: </strong>Our knowledge indicates that the proposed approach is novel, and it can provide new insight into the development of Palbociclib targeting delivery system for cancer treatment.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"16 2","pages":"143-157"},"PeriodicalIF":2.8,"publicationDate":"2023-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10121994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9744140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Conversation on Artificial Intelligence, Chatbots, and Plagiarism in Higher Education.","authors":"Michael R King","doi":"10.1007/s12195-022-00754-8","DOIUrl":"10.1007/s12195-022-00754-8","url":null,"abstract":"","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"16 1","pages":"1-2"},"PeriodicalIF":2.8,"publicationDate":"2023-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9842816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10549738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Applications and Challenges of the Development of <i>In Vitro</i> Tumor Microenvironment Chips.","authors":"Annika Johnson, Samuel Reimer, Ryan Childres, Grace Cupp, Tia C L Kohs, Owen J T McCarty, Youngbok Abraham Kang","doi":"10.1007/s12195-022-00755-7","DOIUrl":"10.1007/s12195-022-00755-7","url":null,"abstract":"<p><p>The tumor microenvironment (TME) plays a critical, yet mechanistically elusive role in tumor development and progression, as well as drug resistance. To better understand the pathophysiology of the complex TME, a reductionist approach has been employed to create <i>in vitro</i> microfluidic models called \"tumor chips\". Herein, we review the fabrication processes, applications, and limitations of the tumor chips currently under development for use in cancer research. Tumor chips afford capabilities for real-time observation, precise control of microenvironment factors (e.g. stromal and cellular components), and application of physiologically relevant fluid shear stresses and perturbations. Applications for tumor chips include drug screening and toxicity testing, assessment of drug delivery modalities, and studies of transport and interactions of immune cells and circulating tumor cells with primary tumor sites. The utility of tumor chips is currently limited by the ability to recapitulate the nuances of tumor physiology, including extracellular matrix composition and stiffness, heterogeneity of cellular components, hypoxic gradients, and inclusion of blood cells and the coagulome in the blood microenvironment. Overcoming these challenges and improving the physiological relevance of <i>in vitro</i> tumor models could provide powerful testing platforms in cancer research and decrease the need for animal and clinical studies.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"16 1","pages":"3-21"},"PeriodicalIF":2.8,"publicationDate":"2022-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9842840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9103334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combining Metformin and Drug-Loaded Kidney-Targeting Micelles for Polycystic Kidney Disease.","authors":"Kairui Jiang, Yi Huang, Eun Ji Chung","doi":"10.1007/s12195-022-00753-9","DOIUrl":"10.1007/s12195-022-00753-9","url":null,"abstract":"<p><strong>Introduction: </strong>Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease that leads to eventual renal failure. Metformin (MET), an AMP-activated protein kinase (AMPK) activator already approved for type 2 diabetes, is currently investigated for ADPKD treatment. However, despite high tolerability, MET showed varying therapeutic efficacy in preclinical ADPKD studies. Thus, newer strategies have combined MET with other ADPKD small molecule drug candidates, thereby targeting multiple ADPKD-associated signaling pathways to enhance therapeutic outcomes through potential drug synergy. Unfortunately, the off-target side effects caused by these additional drug candidates pose a major hurdle. To address this, our group has previously developed kidney-targeting peptide amphiphile micelles (KMs), which displayed significant kidney accumulation <i>in vivo</i>, for delivering drugs to the site of the disease.</p><p><strong>Methods: </strong>To mitigate the adverse effects of ADPKD drugs and evaluate their therapeutic potential in combination with MET, herein, we loaded KMs with ADPKD drug candidates including salsalate, octreotide, bardoxolone methyl, rapamycin, tolvaptan, and pioglitazone, and tested their <i>in vitro</i> therapeutic efficacy when combined with free MET. Specifically, after determining the 40% inhibitory concentration for each drug (IC₄₀), the size, morphology, and surface charge of drug-loaded KMs were characterized. Next, drug-loaded KMs were applied in combination with MET to treat renal proximal tubule cells derived from <i>Pkd1flox/-:TSLargeT</i> mice in 2D proliferation and 3D cyst model.</p><p><strong>Results: </strong>MET combined with all drug-loaded KMs demonstrated significantly enhanced efficacy as compared to free drugs in inhibiting cell proliferation and cyst growth. Notably, synergistic effects were found for MET and KMs loaded with either salsalate or rapamycin as determined by Bliss synergy scores.</p><p><strong>Conclusion: </strong>Together, we show drug synergy using drug-loaded nanoparticles and free MET for the first time and present a novel nanomedicine-based combinatorial therapeutic approach for ADPKD with enhanced efficacy.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s12195-022-00753-9.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"16 1","pages":"55-67"},"PeriodicalIF":2.8,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9842834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9117427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}