International Journal of Biochemistry & Cell Biology最新文献

{"title":"Silencing HMGB1 secretion inhibited EV71-induced blood-brain barrier dysfunction and neural inflammation by depressing astrocyte activation via sHh signal blockage","authors":"Yufeng Zhang ,&nbsp;Yanfang Liu ,&nbsp;Han Wan ,&nbsp;Huiling Deng ,&nbsp;Pengfei Xu ,&nbsp;Lu Cao ,&nbsp;Xiru Yang ,&nbsp;Hui Li","doi":"10.1016/j.biocel.2025.106797","DOIUrl":"10.1016/j.biocel.2025.106797","url":null,"abstract":"<div><div>It is unclear whether high mobility group protein B1 (HMGB1) is associated with the malignant characterization of hand, foot, and mouth disease (HFMD), and whether it plays a key regulatory role in the process of enterovirus 71 (EV71)-induced brain damage. Firstly, we analyzed the correlation between clinical information and HMGB1 concentrations in patients with mild and severe HFMD. Immunofluorescence was used to determine the expression level of HMGB1 in astrocytes. The levels of cellular inflammatory factors (IL-1β, IL-4, IL-6, TNF-α and TGF-β1), chemokines (CCL2, CXCL10 and CXCL12) and adhesion factors (integrin β, P-gp, VCAM-1 and ICAM-1) were detected by ELISA kits. Western blot was used to measure the levels of blood-brain barrier (BBB) stability related factors (retinoic acid (RA), ANG1, ApoE and IGF-1) in astrocytes and BBB structure related proteins (occluding, claudin, PTCH-1 and ZO-1) in endothelial cells. Clinical studies found that the expression of HMGB1 was closely related to the HFMD severity. Knockdown of HMGB1 alleviated EV71-induced neuron damage and inhibited cellular inflammation and apoptosis. Importantly, silencing HMGB1 depressed excessive proliferation and the inflammation response of astrocytes caused by EV71 infection. Furthermore, knockdown of HMGB1 enhanced BBB stability by improving astrocyte adhesion and endothelial tight junctions. Mechanistically, HMGB1 regulated the stability of BBB by regulating sHh signaling and secretion in astrocytes. In conclusion, the level of HMGB1 is closely related to the clinical symptoms of patients with HFMD, and inhibiting the expression of HMGB1 promotes BBB stability by promoting sHh signaling in astrocytes.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"185 ","pages":"Article 106797"},"PeriodicalIF":3.4,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144046249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Restoration of A2M reduces drug resistance and malignancy in paclitaxel-resistant lung cancer cells","authors":"Xiaona Fan ,&nbsp;Hongsheng Xue ,&nbsp;Ziwei Liu ,&nbsp;Ying Zhou ,&nbsp;Xuying Huang ,&nbsp;Xiaomei Dong ,&nbsp;Qianqian Sun ,&nbsp;Jiannan Yao ,&nbsp;Jian Liu","doi":"10.1016/j.biocel.2025.106789","DOIUrl":"10.1016/j.biocel.2025.106789","url":null,"abstract":"<div><div>The development of acquired paclitaxel resistance poses a significant challenge in managing lung cancer clinically. Understanding the mechanism and developing effective strategies to counter paclitaxel resistance are highly desired. To explore the potential mechanisms of acquired paclitaxel resistance, we established a series of lung cancer cell lines exhibiting different levels of resistance to paclitaxel. Transcriptomic RNA-sequencing revealed a progressive decrease in alpha-2-macroglobulin (A2M) levels as paclitaxel resistance advanced in NCI-H446 cells. This was accompanied by the upregulation of known paclitaxel resistance inducers ABCB1, TMEM243, and ID1. A2M loss was further validated in paclitaxel-resistant A549 and HCC827 lung cancer cells. TCGA and CPTAC analyses demonstrated that A2M is downregulated in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), inversely correlating with tumor progression. Restoring A2M expression inhibited proliferation and invasion in paclitaxel-resistant lung cancer cells, suggesting its tumor-suppressing role in lung cancer. Notably, restoring A2M re-suppressed the expression of the paclitaxel resistance mediators (ABCB1, TMEM243 and ID1) in the drug-resistant cells, and re-sensitized them to paclitaxel. In summary, our data indicate that A2M is progressively lost during the development of paclitaxel resistance in lung cancer, and restoring A2M may help overcome this resistance. Thus, A2M deficiency may serve as both a predictor and a therapeutic target for paclitaxel resistance in lung cancer.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"185 ","pages":"Article 106789"},"PeriodicalIF":3.4,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143929467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell transcriptomics and metabolomics reveal the potential role of ASRGL1 in metabolic reprogramming and invasion of nasopharyngeal carcinoma cells","authors":"YingYing Pei ,&nbsp;Chunlin Li ,&nbsp;Bin Zhang ,&nbsp;Qi Zheng ,&nbsp;Shengnan Chen ,&nbsp;Ji Li","doi":"10.1016/j.biocel.2025.106788","DOIUrl":"10.1016/j.biocel.2025.106788","url":null,"abstract":"<div><div>Nasopharyngeal carcinoma (NPC) is an aggressive and highly metastatic malignancy, presenting significant challenges for early diagnosis and treatment. Asparaginase-like protein 1 (ASRGL1) is an important enzyme involved in amino acid metabolism, and previous studies have linked it to the progression of various tumors. However, the specific role of ASRGL1 in NPC remains unclear. This study analyzed multiple publicly available datasets related to NPC. We conducted single-cell RNA sequencing (scRNA-seq) analysis on the GSE150430 dataset to identify different cell subpopulations and examine ASRGL1 expression and its functional implications. The expression of ASRGL1 and its correlation with EMT were validated using transcriptomic data. The expression of ASRGL1 in C666–1 cells was interfered with by siRNA, cell proliferation and invasion were detected by CCK8, EdU, plate cloning, Transwell and scratch method, and EMT was evaluated by detecting the expression of E-cadherin and N-cadherin. Amino acid metabolomics and GC-MS headspace metabolomics were used to analyze the effects of ASRGL1 knockdown on the metabolic pattern of NPC cells. This study found that ASRGL1 was mainly expressed in fibroblasts, epithelial cells and myeloid cells in nasopharyngeal carcinoma (NPC). The ASRGL1-cell gene was significantly enriched in the epithelial-mesenchymal transition pathway. Knocking down ASRGL1 can further inhibit the proliferation, invasion and EMT of C666–1 cells. At the same time, the utilization of various amino acids was significantly reduced, and further GC-MS metabolomics analysis showed that the cell metabolism was unbalanced. This study elucidates the expression characteristics and potential functional roles of asparaginase-like protein 1 (ASRGL1) in nasopharyngeal carcinoma (NPC), providing new insights into its potential as a diagnostic marker and therapeutic target.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"185 ","pages":"Article 106788"},"PeriodicalIF":3.4,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143922373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acalabrutinib alleviates metabolic dysfunction–associated steatotic liver disease by regulating bile acid metabolism","authors":"Yanbo Wang,&nbsp;Shiwei Chen,&nbsp;Bingjue Ye,&nbsp;Zhenggang Yang,&nbsp;Yanning Liu,&nbsp;Guohua Lou,&nbsp;Cheng Zhou,&nbsp;Min Zheng","doi":"10.1016/j.biocel.2025.106786","DOIUrl":"10.1016/j.biocel.2025.106786","url":null,"abstract":"<div><div>Metabolic dysfunction–associated steatotic liver disease (MASLD) is a global epidemic of chronic liver disease currently lacking effective treatment. Evaluating the therapeutic effects of existing drugs on MASLD is a time and cost-effective strategy. Bruton's tyrosine kinase (BTK) is an inflammatory signaling molecule playing an important role in the progression of MASLD. Aclabrutinib, a BTK inhibitor approved for treating mantle-cell lymphoma and chronic lymphocytic leukemia, has not been investigated for its potential to treat MASLD. This study examined the therapeutic effects and mechanisms of aclabrutinib on MASLD using a high-fat diet-induced mouse model. Results demonstrated significant alleviation of pathological parameters associated with MASLD upon administration of aclabrutinib. TSE PhenoMaster results revealed that aclabrutinib increased energy expenditure in mice. Furthermore, aclabrutinib upregulated the expression of genes associated with thermogenesis and lipolysis in adipose tissues. Additionally, it inhibited the transcription of genes related to lipid absorption in the small intestine and liver, while increasing the expression of hormone-sensitive lipase, hepatic nuclear factor 4 alpha and fibroblast growth factor 21 in the liver. Further analysis indicated that aclabrutinib promoted the alternative pathway of bile acid synthesis while restoring gut microbiota homeostasis. The altered bile acid profiles upregulated G protein-coupled bile acid receptor 1 expression in adipose tissues as well as vitamin D receptor expression in liver and small intestine. Our findings suggest that by regulating bile acid metabolism and gut microbiota, aclabrutinib may promote thermogenesis and lipolysis, thereby alleviating MASLD. This study provides novel insights into clinical applications targeting BTK for treating MASLD.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"185 ","pages":"Article 106786"},"PeriodicalIF":3.4,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143947136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Morin inhibits the progression of 5-fluorouracil–resistant colorectal cancer by suppressing autophagy","authors":"Rui Li ,&nbsp;Fengxia Wang ,&nbsp;Lu Huang ,&nbsp;Lvheng Zhao ,&nbsp;Ting Qin ,&nbsp;Shan Liu ,&nbsp;Kunyao Xu ,&nbsp;Bi Wang ,&nbsp;Ling Li ,&nbsp;Sha He","doi":"10.1016/j.biocel.2025.106783","DOIUrl":"10.1016/j.biocel.2025.106783","url":null,"abstract":"<div><h3>Background</h3><div>Resistance to 5-fluorouracil (5-FU) poses a significant challenge in colorectal cancer (CRC) treatment. Morin is a flavonoid with anti-tumor properties. However, its role in overcoming acquired 5-FU resistance in CRC remains unclear.</div></div><div><h3>Methods</h3><div>5-FU-resistant CRC (5-FU/CRC) cell lines (HT29/5-FU and HCT116/5-FU) were established using the IC50 concentration increment method. After treatment with Morin and autophagy inhibitors (3-MA) or agonists (RAPA), cell viability, apoptosis, colony formation, migration, invasion, and autophagy were evaluated. <em>In vivo</em>, xenograft models of 5-FU/CRC assessed Morin's therapeutic effects.</div></div><div><h3>Results</h3><div>5-FU/CRC cells were successfully constructed. Morin inhibited the viability, migration, and invasion of 5-FU/CRC cells and promoted apoptosis. Morin also inhibited autophagy in 5-FU/CRC cells. Besides, autophagy activated by RAPA could eliminate the effect of Morin on 5-FU/CRC cells, while 3-MA enhanced the effects of Morin. In nude mouse models, Morin inhibited the growth and improved the pathological structure of 5-FU/CRC xenografts by inhibiting autophagy.</div></div><div><h3>Conclusion</h3><div>Morin suppresses the progression of 5-FU/CRC by inhibiting autophagy, suggesting its potential as a therapeutic agent to combat 5-FU resistance.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"185 ","pages":"Article 106783"},"PeriodicalIF":3.4,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143940976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of M2 macrophage-mediated mesenchymal stem cell migration: Boldine attenuates elbow heterotopic ossification","authors":"Fengteng Shen ,&nbsp;Yansong Chen ,&nbsp;Zhikun Xu ,&nbsp;Wei Wang ,&nbsp;Guofang Chen ,&nbsp;Fusheng Ye","doi":"10.1016/j.biocel.2025.106787","DOIUrl":"10.1016/j.biocel.2025.106787","url":null,"abstract":"<div><h3>Background</h3><div>Heterotopic ossification (HO) is characterized by abnormal bone formation in soft tissues, often following trauma or surgery. Transforming growth factor-beta (TGF-β) signaling and M2 macrophage polarization play critical roles in the recruitment and differentiation of mesenchymal stromal/progenitor cells (MSPCs), promoting HO.</div></div><div><h3>Methods</h3><div>An elbow joint trauma-induced HO mouse model was established, where model mice were treated with dichloromethylene-bisphosphonate (Cl2MBP) liposomes or PBS liposomes to deplete macrophages. In addition, boldine was administered to evaluate its therapeutic effect on HO formation. Bone marrow mesenchymal stem cells (BMSCs) were also extracted for <em>in vitro</em> experiments. Quantitative real-time PCR (qRT-PCR) and Western blot were conducted to assess gene and protein expression. <em>In vivo</em> methods included Micro-Computed Tomography (Micro-CT) to assess bone formation, histological staining to evaluate tissue changes, immunohistochemistry (IHC) and immunofluorescence to analyze macrophage, CD73⁺ and CD105⁺ cells infiltration. <em>In vitro</em>, BMSCs were identified by flow cytometry and treated with interleukin-10 (IL-10) and/or boldine, and assays such as cell viability (Cell Counting Kit 8 (CCK8)), migration (Transwell), immunofluorescence, ALP staining, and Alizarin Red S staining, were conducted to assess osteogenic differentiation.</div></div><div><h3>Results</h3><div>Boldine treatment significantly reduced HO formation, decreased collagen deposition, and inhibited M2 macrophage infiltration (<em>P</em> &lt; 0.05). <em>In vitro</em>, boldine reduced IL-10-induced cell activity, migration, and osteogenic differentiation of BMSCs and inhibited TGF-β and pSmad2/3/Smad2/3 protein (<em>P</em> &lt; 0.05).</div></div><div><h3>Conclusion</h3><div>Boldine attenuates HO by inhibiting M2 macrophage-mediated MSPC migration and might involve the TGF-β signaling, suggesting its potential as a therapeutic approach for managing HO.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"185 ","pages":"Article 106787"},"PeriodicalIF":3.4,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of long non-coding RNA in lipid metabolism: Implications in leukemia","authors":"Anjani Alluri ,&nbsp;Pallavi Saxena ,&nbsp;Amit Mishra ,&nbsp;Ravi Kumar Gutti","doi":"10.1016/j.biocel.2025.106785","DOIUrl":"10.1016/j.biocel.2025.106785","url":null,"abstract":"<div><div>Cancer has high mortality rate and occupies second position among major diseases. Despite extensive research and therapies, in every nook and corner of the world, death rate is increasing exponentially. Hallmarks of cancer are benchmarks of cancer cells describing the fundamental principle and capabilities of the cells transforming from normal to malignant tumour. One of the major ones among them is the deregulation of cellular metabolism or metabolic reprogramming, involving alterations in glucose and lipid metabolism. Progressive research in this area has visualized the vital role of lncRNAs in lipid metabolism with respect to AML. lncRNAs involve in various cellular processes and also contribute for significant functions of the cell like chromatin remodelling, transcriptional activation and repression, gene regulation, immune response, cell differentiation, and cell cycle regulation, in addition to oncogenic processes such as proliferation, angiogenesis, migration, and apoptosis. Structural similarities are observed among mRNAs and lncRNAs in terms of poly A-tail and 5^’ cap however protein-coding regions are lacking. A large body of evidence has shown that lncRNAs directly or indirectly mediate lipid metabolism by activating downstream genes. Considering their potential involvement in leukemia, these lncRNAs can be explored and considered as biomarkers for therapeutics, prognosis, and diagnosis. The present review is planned to summarize the functional classification of lncRNAs, the role of lipid metabolism in cancer, different lncRNAs involved in leukemia, and different cancer types related to lipid metabolism.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"184 ","pages":"Article 106785"},"PeriodicalIF":3.4,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CAPRIN1/TYMS/MTHFD2 axis promotes EMT process in nasopharyngeal carcinoma development","authors":"Kunrong Wang ,&nbsp;Hanbing Yu ,&nbsp;Shuang Guo ,&nbsp;Guihu Sun ,&nbsp;Hongwei Cao ,&nbsp;Dongsheng Xing ,&nbsp;Dawei Li ,&nbsp;Aihui Yan","doi":"10.1016/j.biocel.2025.106784","DOIUrl":"10.1016/j.biocel.2025.106784","url":null,"abstract":"<div><h3>Background</h3><div>Nasopharyngeal carcinoma (NPC) is a type of malignant tumor occurring in the nasopharynx. It frequently leads to treatment failure after metastasis, often resulting from epithelial-mesenchymal transition (EMT). Thymidylate synthetase (TYMS) is a key enzyme involved in DNA synthesis and replication. Currently, the role of TYMS and its mechanism of upstream and downstream in EMT of NPC is unclear.</div></div><div><h3>Methods</h3><div>NPC cell lines HK-1 and C666–1 were used in this study. Lentivirus carrying TYMS knockdown and overexpressed plasmids were used to regulate TYMS expression. Cell migration and invasion were examined using the wound-healing and Transwell assays, respectively. C666–1 cells were injected into the axilla and tail vein of mice to form subcutaneous tumors and construct lung metastasis model, respectively. RNA immunoprecipitation assay was used to examine the interaction between protein and mRNA. RNA-seq was performed to explore the downstream regulatory mechanism of TYMS.</div></div><div><h3>Results</h3><div>TYMS was highly expressed in NPC tissues. TYMS silencing and upregulation inhibited and promoted EMT processes in NPC cells, respectively, as demonstrated by the expression of EMT-related proteins, including E-cadherin, Slug, MMP2, and MMP9. Cytoplasmic activation/proliferation-associated protein-1 (CAPRIN1), a protein bound with TYMS mRNA, promoted the EMT process in NPC cells. Meanwhile, TYMS knockdown reversed the effect of CAPRIN1 overexpression. Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) was down-regulated following TYMS silencing. MTHFD2 knockdown abolished the effect of TYMS overexpression.</div></div><div><h3>Conclusion</h3><div>CAPRIN1/TYMS/MTHFD2 axis drives the EMT process and thus promotes NPC development, which is a promising target in therapy and adjuvant therapy of NPC.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"185 ","pages":"Article 106784"},"PeriodicalIF":3.4,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-channel smFRET study reveals a compact conformation of EF-G on the ribosome","authors":"Jordan L. Johnson ,&nbsp;Jacob H. Steele ,&nbsp;Ran Lin ,&nbsp;Victor G. Stepanov,&nbsp;Miriam N. Gavriliuc ,&nbsp;Yuhong Wang","doi":"10.1016/j.biocel.2025.106782","DOIUrl":"10.1016/j.biocel.2025.106782","url":null,"abstract":"<div><div>While elongation factor G (EF-G) is crucial for ribosome translocation, the role of its GTP hydrolysis remains ambiguous. EF-G's indispensability is further exemplified by the phosphorylation of human eukaryotic elongation factor 2 (eEF2) at Thr56, which inhibits protein synthesis globally, but its exact mechanism is not clear. In this study, we developed a multi-channel single-molecule FRET (smFRET) microscopy methodology to examine the conformational changes of <em>E. coli</em> EF-G induced by mutations that closely aligned with eEF2's Thr56 residue. We utilized Alexa 488/594 double-labeled EF-G to catalyze the translocation of fMet-Phe-tRNA^Phe-Cy3 inside Cy5-L27 labeled ribosomes, allowing us to probe both processes within the same complex. Our findings indicate that in the presence of either GTP or GDPCP, wild-type EF-G undergoes a conformational extension upon binding to the ribosome to promote normal translocation. On the other hand, the T48E and T48V mutations did not affect GTP/GDP binding or GTP hydrolysis, but impeded Poly(Phe) synthesis and caused EF-G to adopt a unique compact conformation, which was not observed when the mutants interact solely with the SRL. This study provides new insights into EF-G's adaptability and sheds light on the modification mechanism of human eEF2.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"184 ","pages":"Article 106782"},"PeriodicalIF":3.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hematopoietic stem cell conditioned media induces apoptosis in colorectal cancer stem cells via dysregulation of HSP90 and 26S proteasome system","authors":"Sumit Mallick ,&nbsp;Vanya Kadla Narayana ,&nbsp;Akhila Balakrishna Rai ,&nbsp;Shubham Sukerndeo Upadhyay ,&nbsp;Thottethodi Subrahmanya Keshava Prasad ,&nbsp;Sudheer Shenoy P ,&nbsp;Bipasha Bose (Lead contact)","doi":"10.1016/j.biocel.2025.106773","DOIUrl":"10.1016/j.biocel.2025.106773","url":null,"abstract":"<div><div>Cancer stem cells (CSCs) hold a significant role in cancer metastasis, high mortality and severity responsible for therapy resistance and tumour recurrence. The 26S proteasome system plays a major role in protein degradation in normal cells. As most cancers have upregulated 26S proteasome machinery, cancer cells use the 26S proteasome system in their favour for growth support by degrading unwanted proteins, but dysfunction of the 26S proteasome system induces apoptosis in cells. Here, we used hematopoietic stem cells (HSCs) and HSCs-derived conditioned media (CM) to target colorectal cancer stem cells (CRC-CSCs). HSCs are otherwise used extensively to save the lives of patients suffering from hematological malignancies and inherited blood disorders. HSCs-derived conditioned media contains various cytokines, chemokines, and secretory small molecules, which can also target the CRC-CSCs. Moreover, HSCs have exhibited CRC-CSC tropism in vitro in our pilot studies. As therapeutic uses of HSCs for targeting colorectal cancer (CRC) have never been reported, we hypothesized the CRC-CSC targeting properties of HSCs. Our results indicated altered protein function of CRC-CSCs upon co-culture with HSCs. Proteomics approaches showed that HSCs-CM disrupted 26S proteasomal complex and altered the mitochondrial bioenergetics, thereby activating apoptosis in CRC-CSCs. Furthermore, we observed that HSCs-CM significantly induced double-stranded DNA damage and proteasomal degradation, leading to apoptosis and upregulating the autophagy system. This study, hence, provides the prospective targeting of cancer stem cells using HSCs-CM, indicating a possible therapeutic approach.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"184 ","pages":"Article 106773"},"PeriodicalIF":3.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143842684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}