Emma R Belcher, Steven W Hardwick, Taiana Maia de Oliveira, Marko Hyvönen
{"title":"Affinity purification contaminants identified by cryo-EM and mass spectrometry.","authors":"Emma R Belcher, Steven W Hardwick, Taiana Maia de Oliveira, Marko Hyvönen","doi":"10.1042/BSR20260232","DOIUrl":"10.1042/BSR20260232","url":null,"abstract":"<p><p>Affinity chromatography is a powerful and therefore popular method for the purification of proteins for structural studies. The success of the technique relies on the specificity of the interaction between the target protein and the affinity resin. Here, we present the identification of two protein contaminants isolated from HEK293 cell lysate following affinity purification of twin Strep-tagged or FLAG-tagged proteins. The contaminants were identified as human propionyl-coenzyme A carboxylase and protein arginine methyltransferase 5 in complex with methylosome protein 50 (PRMT5:MEP50) via a combination of cryogenic electron microscopy (cryo-EM) data processing and proteomic analyses. This report serves to illustrate how these contaminants may appear in cryo-EM datasets and to highlight the paramount importance of affinity chromatography resin specificity for efficient protein purification.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13259823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148052306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mohamed S Attia, Brett Dyer, Nigel McMillan, Matthew Zunk
{"title":"A systematic review and meta-analysis of shRNA-IL-6-engineered CAR-T cells for B-cell acute lymphoblastic leukemia: a stepping stone toward risk-free immunotherapy.","authors":"Mohamed S Attia, Brett Dyer, Nigel McMillan, Matthew Zunk","doi":"10.1042/BSR20260143","DOIUrl":"10.1042/BSR20260143","url":null,"abstract":"<p><p>Clinical application of chimeric antigen receptor (CAR)-T cells, especially those targeting CD19, stands as a breakthrough in treating relapsed or refractory B-cell acute lymphoblastic leukemia. Yet, preventing immune-related adverse events, like severe cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), remains a significant concern. This meta-analysis looked at the efficacy and safety of interleukin-6 knockdown CAR-T therapy. The study's primary outcomes included the incidence of CRS, ICANS, and the number of patients achieving an early complete response (CR) and overall response (OR) rates at one-month post-infusion of anti-CD19 shRNA-engineered CAR-T cells. The random-effects model was used to estimate summary effects. Certainty of evidence was assessed using GRADE. Out of 275 studies screened, 7 studies were eligible (n = 178 patients). The pooled OR and CR rates were 88% (95% CI: 81-92) and 84% (95% CI: 78-89), respectively, with no heterogeneity detected. Among 147 patients, 116 (78%, 95% CI: 68-85) developed CRS, whereas 46 (28%, CI: 21%-35%) out of 178 were affected by severe grades (≥3). While ICANS was detected in 13 out of 159 patients (13%, CI: 2%-51%, I2 = 69.5%), three studies confirmed the absence of severe grade ICANS. According to GRADE assessment, current analysis presents low certainty of evidence supporting investigated outcomes, except for ICANS (any grade) that was deemed very low. More importantly, as all included studies were conducted in China, the findings may not be readily generalizable to other healthcare systems and ethnically diverse populations. Therefore, our confidence in the effect estimates is limited and it may vary from true estimates.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13199798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yonika A Larasati, Alexey Koval, Vladimir L Katanaev
{"title":"Small-molecule inhibitor of Gαo for GNAO1 encephalopathy.","authors":"Yonika A Larasati, Alexey Koval, Vladimir L Katanaev","doi":"10.1042/BSR20250392","DOIUrl":"10.1042/BSR20250392","url":null,"abstract":"<p><p>GNAO1-related neurodevelopmental disorders are caused by mutations in the GNAO1 gene encoding the major neuronal G protein, Gαo. GNAO1 encephalopathies manifest in a range of symptoms, including epilepsy, movement disorder, hypotonia, and developmental delay, affecting >400 patients worldwide to date. A growth in the number of diagnosed cases is expected due to the wider availability of whole genome sequencing. One of the most recurrent pathogenic variants causing GNAO1 encephalopathy is an intronic mutation c.724-8G>A, which results in an in-frame insertion of two amino acid residues, Pro-Gln, after Thr241: Gαo[T241_N242insPQ]. We previously performed in-depth profiling of Gαo[insPQ] using structural, biochemical, and cellular studies. Compared with the wild-type protein, Gαo[insPQ] exhibits faster GTP binding and decreased hydrolysis. Importantly, Gαo[insPQ] is deficient in interacting with regulator of G protein signaling (RGS), GTPase-activating proteins that deactivate Gαo. These defects render Gαo[insPQ] a constitutively active mutant loaded with GTP in the G protein signaling. Patients harboring Gαo[insPQ] variant are in urgent need of novel therapy as they are refractory to available medications. In the present study, we performed a high-throughput screening to find molecules that might suppress the constitutive GTP loading by Gαo[insPQ]. We used a high-diversity chemical library of 54080 compounds, identifying a novel compound, N-[5-(2-methylpropyl)-1,3,4-thiadiazol-2-yl]-1H-1,2,3-benzotriazole-5-carboxamide, that decreases the GTP binding rate of Gαo, likely acting as a competitive inhibitor with higher selectivity to the pathogenic protein. This small-molecule inhibitor of Gαo opens new opportunities to drug discovery towards Gαo-dependent pathologies.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13185127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Isoprenaline alleviates diabetic kidney disease via multi-target inhibition of the cGAS-STING pathway.","authors":"Runtao Ma, Yue Song, Lijun Zhang, Peng Wang, Jiaqi Chen, Tianqi Chen, Guangyao Zhu, Qingrong Pan, Mengyu Ma, Qigui Mo, Surui Lu, Xuanjie Yu, Yi Guo","doi":"10.1042/BSR20250174","DOIUrl":"10.1042/BSR20250174","url":null,"abstract":"<p><p>Diabetic kidney disease (DKD) is a common microvascular complication of diabetes and is closely linked to chronic inflammation. The present study examined how the β-adrenergic receptor agonist isoprenaline (ISO) protected against DKD by regulating the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway through multiple targets. In a streptozotocin-induced diabetic mouse model, ISO treatment improved glomerulosclerosis, reduced podocyte injury and proteinuria, and suppressed renal inflammation. Network pharmacology and molecular docking suggested that, besides activating ADRB1/2, ISO may interact with AKT1, SRC, GSK3β, and EGFR, which are involved in cGAS-STING signaling regulation. These findings indicate that ISO alleviates DKD by inhibiting excessive activation of the cGAS-STING pathway through multi-target coordination, providing a new perspective for therapeutic development.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13161330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147376021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Haote Liang, Hang Huang, Yeping Li, Yongyong Lu, Tingyu Ye
{"title":"Retraction: CircRNA_0058063 functions as a ceRNA in bladder cancer progression via targeting miR-486-3p/FOXP4 axis.","authors":"Haote Liang, Hang Huang, Yeping Li, Yongyong Lu, Tingyu Ye","doi":"10.1042/BSR20193484_RET","DOIUrl":"10.1042/BSR20193484_RET","url":null,"abstract":"","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":"46 5","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13189525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Natalia Papadopoulos, Niki Sarri, Johan Lennartsson, Carl-Henrik Heldin
{"title":"G3BP1 is a SWI/SNF-bound regulator of transcription that modulates activation of STATs.","authors":"Natalia Papadopoulos, Niki Sarri, Johan Lennartsson, Carl-Henrik Heldin","doi":"10.1042/BSR20250290","DOIUrl":"10.1042/BSR20250290","url":null,"abstract":"<p><p>RAS GTPase-activating protein-binding protein 1 (G3BP1) is a component of the RAS signaling pathway and a phosphorylation-dependent RNA/DNA endoribonuclease that links signal transduction and RNA metabolism. We identified G3BP1 as a nuclear interactor of platelet-derived growth factor receptor-β, forming a complex with BAF155, a component of the SWI/SNF chromatin remodeling complex, as well as with the transcription factor STAT3. Depletion of G3BP1 in human primary fibroblasts AG1523 reduced PDGF-BB-induced activation of STAT3 while increasing mRNA levels of FOS, MYC, and CCND1, which encode proteins involved in growth stimulation. Both STAT1 and cyclin D1 mRNA and protein levels were elevated upon G3BP1 knockdown, identifying G3BP1 as a negative regulator of STAT1 and cyclin D1 expression. G3BP1 depletion did not abolish PDGF-BB-induced proliferation of human primary fibroblasts. Thus, G3BP1 interacts with the SWI/SNF chromatin remodeling complex in the nucleus and regulates cell growth pathways by modulating STAT signaling and transcription of growth-associated genes.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13161325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147637791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shimaa O Ali, Doaa Hegazy, Ibrahim S Kamel, Naglaa H Shalan, Asmaa A ElMonier
{"title":"α-Linolenic acid-driven nano-liposomes from purslane seed oil modulate p-JAK2/p-STAT3 to combat acute liver failure.","authors":"Shimaa O Ali, Doaa Hegazy, Ibrahim S Kamel, Naglaa H Shalan, Asmaa A ElMonier","doi":"10.1042/BSR20250383","DOIUrl":"10.1042/BSR20250383","url":null,"abstract":"<p><p>Acute liver failure (ALF) is a serious illness characterized by extensive liver cell damage and inflammation. The present study highlights the potential of purslane seed oil extract-Pluronic-modulated liposomes (PSE-PMLs) to protect against thioacetamide (TAA)-induced ALF in rats. Four groups of rats were used in the present study: normal control (NC), TAA-induced ALF, silymarin (SIL), and PSE-PML groups. SIL- and PSE-PML-pretreated groups were orally pre-administered SIL (200 mg/kg) and PSE-PMLs (500 mg/kg), respectively, for 7 days. After these pretreatments, all groups except the NC group were injected intraperitoneally with TAA (350 mg/kg) to induce ALF. Serum levels of liver biochemical markers and inflammatory cytokines, interleukin-4, and interferon-gamma were estimated. Additionally, the hepatic malondialdehyde, superoxide dismutase activity, peroxisome proliferator-activated receptor-gamma coactivator 1-alpha, phosphorylated Janus kinase 2, phosphorylated signal transducer and activator of transcription 3, peroxisome proliferator-activated receptor-gamma, tumor protein p53, active cysteine-aspartic acid protease 3, and B-cell lymphoma 2 were assessed. A histopathological examination of the liver was also performed. The study found that pretreatment with PSE-PMLs mitigated TAA-induced biochemical and histopathological alterations, alleviating oxidative stress, dampening the overproduction of pro-inflammatory cytokines, and amending liver cell apoptosis. These pioneering findings suggest that PSE-PMLs are a promising prophylactic agent against ALF, warranting further studies in the post-injury models. The phytochemical profiling, gas chromatography-mass spectrometry, of purslane seed oil revealed α-linolenic acid (∼98%) as the predominant component, with additional sterols, tocopherols, and phenolic acids that may underlie its strong antioxidant and hepatoprotective effects.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13161346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147519699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hui Lu, Yueyue Zhang, Boying Xu, Di Tian, Yang Xia, Tetsuya Yomo, Jian Xu
{"title":"Conserved rod-to-spherical shape transitions in Escherichia coli through primordial experimental adaptations.","authors":"Hui Lu, Yueyue Zhang, Boying Xu, Di Tian, Yang Xia, Tetsuya Yomo, Jian Xu","doi":"10.1042/BSR20260045","DOIUrl":"10.1042/BSR20260045","url":null,"abstract":"<p><p>Cell shape plays a fundamental role in bacterial physiology, yet the evolutionary stability of morphological adaptations remains poorly understood. Our previous work suggested that Escherichia coli can evolve a spherical form under primordial-like conditions. Here, we extended experimental evolution for approximately 1000 generations in oleic acid vesicle (OAV)-supplemented media mimicking primordial environments, followed by 500 generations in glucose. We observed a robust and stable transition from rod-shaped to spherical morphology that persisted despite environmental reversal. This morphological shift was accompanied by mutations in cell-shape-related genes, and no reversion to the ancestral rod shape was observed during evolution in glucose, where mutations primarily affected metabolic and transcriptional pathways. These findings show that environmental pressures can drive heritable and evolutionarily stable morphological changes in bacteria. Our work provides insight into the genetic and environmental factors shaping bacterial cell geometry and is consistent with, though not conclusive for, the possibility that primordial cells may have been spherical.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13181355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}