Integrative biology : quantitative biosciences from nano to macro最新文献

{"title":"The creation and validation of a fully animal component-free media for select adherent cell types.","authors":"Nicolette B Mogilever, Marie-Hélène Godin Pagé, Anjolaoluwatikiitan Solola, Andrew E Pelling","doi":"10.1093/intbio/zyaf009","DOIUrl":"10.1093/intbio/zyaf009","url":null,"abstract":"<p><p>Fetal Bovine Serum (FBS) is one of the most commonly used media supplement for the maintenance of mammalian cell types, yet the expensive costs, ethical concerns, and lot-to-lot variation have provoked a clear need for a serum that is standardized and derived from non-animal sources. Several serum-free formulations have been developed in the past, however they are often cell type specific, contain animal-derived components, and lack long-term culture validation. In this study, we developed a novel animal component-free (ACF) media and investigated its effectiveness on four commonly used mammalian cell lines via long-term (up to 90 days) morphological, transcriptomic, and proliferative analyses. Cells cultured in our ACF medium exhibited comparable cellular morphologies and equal or greater growth rates compared with cells cultured with FBS. Additionally, differentially expressed genes between the FBS-grown and ACF-grown groups were predominantly associated with functions linked to proliferation and cell attachment. While the tested cells were initially derived using conventional methods and include non-human lines, this study demonstrates that our medium supports long-term culture without animal-derived supplements. The findings from this study indicate that this medium is a suitable replacement to FBS-containing medium for several common cell lines. Insight Box Traditional cell culture methods often rely on animal-derived components, which can pose ethical and economic challenges. The use of animal serum in vitro is needed to supply nutrients to cells but raises concerns about animal welfare and introduces variability and contaminants that can negatively affect downstream applications. This study presents a novel animal component-free medium designed to support the growth of adherent cell types, providing a sustainable alternative to serum. Here, we demonstrate long-term cell viability, normal morphology, and differential gene expression patterns indicative of enhanced proliferation and attachment in cells cultured in 2D environments. By addressing the demand for ethical and reproducible cell culture methods, this research aims to contributes to the broader adoption of sustainable practices in biotechnology.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":"17 ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KCTD10 promoting PD-L1 expression in colorectal cancer enhanced the anti-tumor effect of PD-1 antibody.","authors":"Zihao Yin, Rongyu Su, Shengwen Long, Guo Chen, Shuanglin Xiang","doi":"10.1093/intbio/zyaf014","DOIUrl":"10.1093/intbio/zyaf014","url":null,"abstract":"<p><p>Colorectal cancer is a highly prevalent malignant tumor of the digestive tract worldwide. Immunotherapy has emerged as a critical therapeutic approach for CRC patients. We observed that KCTD10 expression is significantly downregulated in colorectal cancer tissues compared to normal tissues, and patients with higher KCTD10 expression exhibited prolonged survival. To investigate its functional role, we established stable KCTD10-overexpressing CT26 and SW480 colorectal cancer cell lines. Both in vitro and in vivo experiments demonstrated that KCTD10 overexpression suppresses colorectal cancer progression and inhibits the EMT process. Notably, KCTD10 overexpression upregulated PD-L1 expression and synergistically enhanced the therapeutic efficacy of anti-PD-1 treatment. Our findings reveal that KCTD10 functions as a tumor suppressor in colorectal cancer pathogenesis. Mechanistically, KCTD10 potentiates the antitumor efficacy of anti-PD-1 immunotherapy by upregulating PD-L1 expression, thereby proposing a novel therapeutic target and suggesting a promising combination strategy for CRC treatment. Insight box KCTD10 can inhibit the development of colorectal cancer and the EMT process. And the over-expression of KCTD10 increased the expression of PD-L1, improved the efficacy of PD-1 treatment.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":"17 ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144839868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolution and emergence: higher order information structure in protein interactomes across the tree of life.","authors":"Brennan Klein,&nbsp;Erik Hoel,&nbsp;Anshuman Swain,&nbsp;Ross Griebenow,&nbsp;Michael Levin","doi":"10.1093/intbio/zyab020","DOIUrl":"https://doi.org/10.1093/intbio/zyab020","url":null,"abstract":"<p><p>The internal workings of biological systems are notoriously difficult to understand. Due to the prevalence of noise and degeneracy in evolved systems, in many cases the workings of everything from gene regulatory networks to protein-protein interactome networks remain black boxes. One consequence of this black-box nature is that it is unclear at which scale to analyze biological systems to best understand their function. We analyzed the protein interactomes of over 1800 species, containing in total 8 782 166 protein-protein interactions, at different scales. We show the emergence of higher order 'macroscales' in these interactomes and that these biological macroscales are associated with lower noise and degeneracy and therefore lower uncertainty. Moreover, the nodes in the interactomes that make up the macroscale are more resilient compared with nodes that do not participate in the macroscale. These effects are more pronounced in interactomes of eukaryota, as compared with prokaryota; these results hold even after sensitivity tests where we recalculate the emergent macroscales under network simulations where we add different edge weights to the interactomes. This points to plausible evolutionary adaptation for macroscales: biological networks evolve informative macroscales to gain benefits of both being uncertain at lower scales to boost their resilience, and also being 'certain' at higher scales to increase their effectiveness at information transmission. Our work explains some of the difficulty in understanding the workings of biological networks, since they are often most informative at a hidden higher scale, and demonstrates the tools to make these informative higher scales explicit.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"283-294"},"PeriodicalIF":2.5,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39745285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune cell mediated cabozantinib resistance for patients with renal cell carcinoma.","authors":"Keon Young Park,&nbsp;Hunter O Hefti,&nbsp;Peng Liu,&nbsp;Karina M Lugo-Cintrón,&nbsp;Sheena C Kerr,&nbsp;David J Beebe","doi":"10.1093/intbio/zyab018","DOIUrl":"https://doi.org/10.1093/intbio/zyab018","url":null,"abstract":"<p><p>Renal cell carcinoma (RCC) is the third most common genitourinary cancer in the USA. Despite recent advances in the treatment for advanced and metastatic clear cell RCC (ccRCC), the 5-year relative survival rate for the distant disease remains at 12%. Cabozantinib, a tyrosine kinase inhibitor (TKI), which is one of the first-line therapies approved to treat advanced ccRCC as a single agent, is now being investigated as a combination therapy with newer immunotherapeutic agents. However, not much is known about how cabozantinib modulates the immune system. Here, we present a high throughput tri-culture model that incorporates cancer cells, endothelial cells, and patient-derived immune cells to study the effect of immune cells from patients with ccRCC on angiogenesis and cabozantinib resistance. We show that circulating immune cells from patients with ccRCC induce cabozantinib resistance via increased secretion of a set of pro-angiogenic factors. Using multivariate partial least square regression modeling, we identified CD4+ T cell subsets that are correlated with cabozantinib resistance and report the changes in the frequency of these populations in ccRCC patients who are undergoing cabozantinib therapy. These findings provide a potential set of biomarkers that should be further investigated in the current TKI-immunotherapy combination clinical trials to improve personalized treatments for patients with ccRCC.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"259-268"},"PeriodicalIF":2.5,"publicationDate":"2021-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8730366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39743590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Creation of a synthesis-friendly inflammation-inducible promoter suitable for cell therapy.","authors":"Anish Jadav,&nbsp;Kevin Truong","doi":"10.1093/intbio/zyab015","DOIUrl":"https://doi.org/10.1093/intbio/zyab015","url":null,"abstract":"<p><p>The development of 'smart' cell-based therapeutics requires cells that first recognize conditions consistent with disease (e.g. inflammation) and then subsequently release therapeutic proteins, thereby reducing potential toxicity from otherwise continuous expression. Promoters containing NF-κB response elements are often used as reporters of inflammation; however, endogenous promoters have crosstalk with other pathways, and current synthetic promoters have many exact sequence repeats of NF-κB response elements which make them both difficult to synthesize and inherently genetically unstable. Herein, a synthesis-friendly inflammation-inducible promoter (named SFNp) was created by the packing of 14 NF-κB response elements, which have no repeats >9 bp, followed by a minimal cytomegalovirus promoter. In stably expressing human embryonic kidney 293 cells, we assessed the ability of SFNp to inducibly transcribe genes for reporting expression, changing cell morphology, and performing cell fusion. These experiments represent simple milestones for potentially using SFNp in the development of cell-based therapeutics. As strongly repeated DNA can compromise the long-term stability of genetic circuits, new designs used in 'smart' cell therapy will become more reliant on synthesis-friendly components like SFNp.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"230-236"},"PeriodicalIF":2.5,"publicationDate":"2021-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8521041/pdf/zyab015.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39505549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel two-layer-integrated microfluidic device for high-throughput yeast proteomic dynamics analysis at the single-cell level.","authors":"Kaiyue Chen,&nbsp;Nan Rong,&nbsp;Shujing Wang,&nbsp;Chunxiong Luo","doi":"10.1093/intbio/zyaa018","DOIUrl":"https://doi.org/10.1093/intbio/zyaa018","url":null,"abstract":"<p><p>Current microfluidic methods for studying multicell strains (e.g., m-types) with multienvironments (e.g., n-types) require large numbers of inlets/outlets (m*n), a complicated procedure or expensive machinery. Here, we developed a novel two-layer-integrated method to combine different PDMS microchannel layers with different functions into one chip by a PDMS through-hole array, which improved the design of a PDMS-based microfluidic system. Using this method, we succeeded in converting 2 × m × n inlets/outlets into m + n inlets/outlets and reduced the time cost of loading processing (from m × n to m) of the device for studying multicell strains (e.g., m-types) in varied multitemporal environments (i.e., n-types). Using this device, the dynamic behavior of the cell-stress-response proteins was studied when the glucose concentration decreased from 2% to a series of lower concentrations. Our device could also be widely used in high-throughput studies of various stress responses, and the new concept of a multilayer-integrated fabrication method could greatly improve the design of PDMS-based microfluidic systems.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"241-249"},"PeriodicalIF":2.5,"publicationDate":"2020-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/intbio/zyaa018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38439189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fingerprinting microbiomes towards screening for microbial antibiotic resistance.","authors":"Naifu Jin,&nbsp;Dayi Zhang,&nbsp;Francis L Martin","doi":"10.1039/c7ib00009j","DOIUrl":"https://doi.org/10.1039/c7ib00009j","url":null,"abstract":"<p><p>There is an increasing need to investigate microbiomes in their entirety in a variety of contexts ranging from environmental to human health scenarios. This requirement is becoming increasingly important with the emergence of antibiotic resistance. In general, more conventional approaches are too expensive and/or time-consuming and often predicated on prior knowledge of the microorganisms one wishes to study. Herein, we propose the use of biospectroscopy tools as relatively high-throughput, non-destructive approaches to profile microbiomes under study. Fourier-transform infrared (FTIR) or Raman spectroscopy both generate fingerprint spectra of biological material and such spectra can readily be subsequently classed according to biochemical changes in the microbiota, such as emergence of antibiotic resistance. FTIR spectroscopy techniques generally can only be applied to desiccated material whereas Raman approaches can be applied to more hydrated samples. The ability to readily fingerprint microbiomes could lend itself to new approaches in determining microbial behaviours and emergence of antibiotic resistance.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"406-417"},"PeriodicalIF":2.5,"publicationDate":"2017-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/c7ib00009j","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34976390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crosstalk of two-component signal transduction systems in regulating central carbohydrate and energy metabolism during autotrophic and photomixotrophic growth of Synechocystis sp. PCC 6803.","authors":"Guangsheng Pei,&nbsp;Xiangfeng Niu,&nbsp;Yuqing Zhou,&nbsp;Lei Chen,&nbsp;Weiwen Zhang","doi":"10.1039/c7ib00049a","DOIUrl":"https://doi.org/10.1039/c7ib00049a","url":null,"abstract":"<p><p>Unicellular model cyanobacterium Synechocystis sp. PCC 6803 has received considerable attention as a sustainable energy resource because of its photosynthetic machinery. However, two-component signal transduction systems (TCSTSs) in regulating central carbohydrate and energy metabolism of cyanobacteria are still poorly understood due to their diversity and functional complication. In this study, by comparing the growth of knockout mutants of 44 response regulators (RRs) of TCSTSs in Synechocystis, several RR mutants demonstrating differential growth patterns were identified under auto- or photomixotrophic conditions. However, in spite of no growth difference observed for the remaining RR mutants, liquid chromatography-mass spectrometry based metabolomic profile analysis showed that a widespread crosstalk of TCSTSs in regulating central carbohydrate and energy metabolism of Synechocystis was identified, while most of them showed diverse patterns during different trophic types or growth stages. Furthermore, an integrative analysis between evolutionary relationships and metabolomic profiles revealed some pairs of paralogous RRs with highly functional convergence, suggesting the possible conserved functions of Synechocystis TCSTSs during evolution. This study laid an important basis for understanding the function of TCSTSs in photosynthetic cyanobacteria.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"485-496"},"PeriodicalIF":2.5,"publicationDate":"2017-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/c7ib00049a","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34978372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing endogenous signals from hepatocytes using a low volume multi-well plate.","authors":"Pantea Gheibi,&nbsp;Kyung Jin Son,&nbsp;Gulnaz Stybayeva,&nbsp;Alexander Revzin","doi":"10.1039/c7ib00010c","DOIUrl":"https://doi.org/10.1039/c7ib00010c","url":null,"abstract":"<p><p>Hepatocytes are highly differentiated epithelial cells that lose their phenotype and function when removed from the in vivo environment. Given the importance of hepatic cultures for drug toxicity, bioartificial liver assist devices and basic biology studies, considerable efforts have been focused on the maintenance of hepatic function in vitro. The methods used to date include co-cultivation of hepatocytes with stromal cells, organizing these cells into spheroids and imbedding them into bioactive gels. Our team has recently demonstrated that primary rat hepatocytes confined to microfluidic channels in the absence of convection maintained the epithelial phenotype through upregulation of endogenous signals including hepatocyte growth factor (HGF). The objective of the present study was to transition from microfluidic devices, which are somewhat specialized and challenging to use, towards low volume multiwell plates ubiquitous in biology laboratories. Using a combination of 3D printing and micromolding we have constructed inserts that can be placed into standard 12-well plates and can be used to create low volume culture conditions under which primary hepatocytes maintained a differentiated phenotype. This phenotype enhancement was confirmed by hepatic function assays including albumin synthesis and expression. Importantly we confirmed upregulation of HGF inside the low volume culture plates and demonstrated that inhibition of HGF signaling degraded the hepatic phenotype in our cell culture platform. Overall, this study outlines a new cell culture system that leverages the low volume effects of microfluidic channels in a multiwell plate format. Beyond hepatocytes, such a system may be of use in the maintenance of other difficult-to-culture cells including stem cells and primary cancer cells.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"427-435"},"PeriodicalIF":2.5,"publicationDate":"2017-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/c7ib00010c","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34865684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemical genomic analysis of GPR35 signaling.","authors":"Heidi Haibei Hu,&nbsp;Huayun Deng,&nbsp;Shizhang Ling,&nbsp;Haiyan Sun,&nbsp;Terry Kenakin,&nbsp;Xinmiao Liang,&nbsp;Ye Fang","doi":"10.1039/c7ib00005g","DOIUrl":"https://doi.org/10.1039/c7ib00005g","url":null,"abstract":"<p><p>GPR35, a family A orphan G protein-coupled receptor, has been implicated in inflammatory, neurological, and cardiovascular diseases. However, not much is known about the signaling and functions of GPR35. We performed a label-free kinome short hairpin RNA screen and identified a putative signaling network of GPR35 in HT-29 cells, some of which was validated using gene expression, biochemical and cellular assays. The results showed that GPR35 induced hypoxia-inducible factor 1α, and was involved in synaptic transmission, sensory perception, the immune system, and morphogenetic processes. Collectively, our data suggest that GPR35 may play an important role in response to hypoxic stress and be a potential target for the treatment of inflammatory, cardiovascular, and neurological disorders.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"451-463"},"PeriodicalIF":2.5,"publicationDate":"2017-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/c7ib00005g","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34928719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}