Yubing Liu , Vidhi Pareek , Dipankar Bhowmik , Xin Zhang , Stephen J. Benkovic
{"title":"Purinosomes and lysosomes interact to maintain the purine pools","authors":"Yubing Liu , Vidhi Pareek , Dipankar Bhowmik , Xin Zhang , Stephen J. Benkovic","doi":"10.1016/j.biocel.2025.106830","DOIUrl":"10.1016/j.biocel.2025.106830","url":null,"abstract":"<div><div>Purines are the building blocks of DNA/RNA and hence essential metabolites. While the contributions of external purine salvage as well as the <em>de novo</em> purine biosynthesis (DNPB) have been widely studied, the contribution of lysosome mediated DNA/RNA digestion and external reabsorption into the cytosol remains unknown. Here, we address that question as well as the role of lysosome-mediated purine recycling and its coordination with DNPB in maintaining total purine pools in human cancer cell lines. By combining in-cell stable isotope incorporation assay with quantitative metabolomics we show: cellular uptake of external purines and their internal generation are equivalent; an upregulation in lysosome biogenesis that functions in response to purine deficiency caused by methotrexate (MTX) and lometrexol (LTX) treatment. This leads to increased RNA digestion as visualized by a newly developed intracellular RNA-FRET oligo assay. Interestingly, downregulation of lysosomal RNase activity through knockdown of RNAseT2 increased RNA accumulation and a compensating increase in DNPB.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"186 ","pages":"Article 106830"},"PeriodicalIF":3.4,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585527","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":"Overexpression of PBX1 attenuates oxidative stress and apoptosis in diabetic cardiomyopathy by transcriptionally inhibiting TXNIP","authors":"Rui Zhou, Xiuzhu Wang, Nannan Li","doi":"10.1016/j.biocel.2025.106828","DOIUrl":"10.1016/j.biocel.2025.106828","url":null,"abstract":"<div><div>Diabetic cardiomyopathy (DCM) is a cardiovascular disease specific to patients with diabetes. The pathophysiology of DCM is significantly influenced by oxidative stress and apoptosis, which are critical mechanisms underlying the disease. PBX homeobox 1 (PBX1) is a homeodomain transcription factor, which plays a crucial role in regulating various biological processes. However, the precise molecular mechanism of PBX1 in DCM is still unclear. In this study, we investigated the protective effect of PBX1 against cardiac injury. Male C57BL/6 mice subjected to streptozotocin were used to simulate DCM <em>in vivo</em>. Genetic manipulation of PBX1 mediated by the adeno-associated virus-based vectors was employed to overexpress PBX1 in mice. The findings indicated that PBX1 expression was significantly downregulated in the left ventricular tissues of DCM mice, and overexpression of PBX1 mitigated cardiac fibrosis and enhanced cardiac function. Additionally, our results demonstrated that PBX1 overexpression effectively reduced oxidative stress and apoptosis in DCM-affected mice. To mimic DCM <em>in vitro</em>, human cardiomyocytes AC16 cells were treated with high glucose (HG), and results obtained <em>in vitro</em> were consistent with those <em>in vivo.</em> Mechanistically, PBX1 could bind to the promoter region of thioredoxin interacting protein (TXNIP) and exerted a negative regulatory effect on TXNIP transcription. In conclusion, these results suggest that overexpression of PBX1 attenuates oxidative stress and apoptosis in DCM progression by transcriptionally inhibiting TXNIP expression. PBX1 may be a novel therapeutic candidate for DCM treatment.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"186 ","pages":"Article 106828"},"PeriodicalIF":3.4,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144565403","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}
Amrutha Arjunan , Ganesh Venkatraman , Leena Dennis Joseph , Lakshmi R. Perumalsamy
{"title":"Mitochondrial homeostasis and their impact on gastric carcinoma","authors":"Amrutha Arjunan , Ganesh Venkatraman , Leena Dennis Joseph , Lakshmi R. Perumalsamy","doi":"10.1016/j.biocel.2025.106827","DOIUrl":"10.1016/j.biocel.2025.106827","url":null,"abstract":"<div><div>Gastric cancer is the fifth most diagnosed cancer and the third most common cause of cancer-related deaths worldwide. Mitochondrial dysfunction, with its impaired energy production and increased oxidative stress, fuels the development of gastric tumours. Gastric cancer exhibits dysregulated mitochondrial functions, which contribute to metabolic reprogramming, decreased apoptosis sensitivity, therapeutic resistance, and enhanced tumour progression and metastasis. In addition, aberrations in mitochondrial DNA, respiratory chain complexes, and epigenetic alterations foster a pro-tumorigenic microenvironment. Although significant progress has been made in understanding the various molecular mechanisms involved in gastric carcinogenesis, further studies are needed to elucidate mitochondrial homeostasis in gastric cancer. Unravelling mitochondrial intricacies in gastric cancer could open the development of definitive diagnostic and therapeutic interventions driving tumour growth. This review focuses on investigating the altered mitochondrial functionalities in gastric cancer.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"186 ","pages":"Article 106827"},"PeriodicalIF":3.4,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568095","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":"Therapeutic potential of TIM-3 inhibition in cancer, viral infections, and autoimmune disorders","authors":"Ashira Manzoor, Khaled Barakat","doi":"10.1016/j.biocel.2025.106826","DOIUrl":"10.1016/j.biocel.2025.106826","url":null,"abstract":"<div><div>TIM-3 (T cell immunoglobulin and mucin domain protein-3) is a potent checkpoint receptor that functions as a negative regulator of the immune response. Numerous immune cells, including monocytes, TH17 (T helper 17) cells, mast cells, myeloid cells, and Treg (regulatory T) cells, express TIM-3. It consists of four ligands: HMGB1 (High Mobility Group Protein B1), PtdSer (Phosphatidylserine), Galectin-9, and CEACAM-1 (Carcinoembryonic Antigen Cell Adhesion Molecule 1). Research has shown TIM-3's role in cancers, chronic viral infections, and autoimmune disorders. Inhibiting TIM-3, therefore, is a therapeutic approach in the current immunotherapy, particularly when combined with other immune checkpoint inhibitors. The review summarizes its function in different disorders and its potential signaling mechanisms.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"186 ","pages":"Article 106826"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144561829","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}
Zhuowei Shao , Jiankui Ye , Yili Wu , Yu Chen , Rong Wang , Shuai Fang , Shibo Wu
{"title":"SPDYE3 promotes cell cycle and LUSC progression by regulating the CDC25C/CDK1 pathway","authors":"Zhuowei Shao , Jiankui Ye , Yili Wu , Yu Chen , Rong Wang , Shuai Fang , Shibo Wu","doi":"10.1016/j.biocel.2025.106825","DOIUrl":"10.1016/j.biocel.2025.106825","url":null,"abstract":"<div><h3>Background</h3><div>Lung cancer is the primary reason for global cancer-related deaths. Targeted therapy is currently absent for lung squamous cell carcinoma (LUSC), a significant pathological subtype of lung cancer. The gene SPDYE3, a member of the Speedy/Ringo gene family, is highly expressed in different cancer tissues and functions as a cell cycle regulator. However, the potential mechanisms and clinical significance of SPDYE3 in LUSC remain unknown.</div></div><div><h3>Method</h3><div>Gene chip technology was used to detect the expression profiles of RNA in saliva, plasma, and normal controls of LUSC patients. Real-time quantitative polymerase chain reaction(qRT-PCR) was utilized to examine the expression and significance of SPDYE3 in the early diagnosis of LUSC. Furthermore, additional experiments were performed in vitro and in vivo to further assess the impact of SPDYE3 on the proliferation and cell cycle of LUSC. Further investigations were performed using IP, mass spectrometry analysis, and Western blotting to explore the interaction between SPDYE3 and cell division cycle 25 C (CDC25C).</div></div><div><h3>Result</h3><div>Our data showed that SPDYE3 is upregulated in LUSC tissues, plasma, and cells. SPDYE3 exhibited diagnostic usefulness, achieving an Area Under the Curve (AUC) of 0.7288. Experiments conducted in vitro and in vivo revealed that SPDYE3 enhances the growth and advancement of the cell cycle in LUSC cells. SPDYE3 mechanistically stimulates the activation of cyclin-dependent kinase 1 (CDK1) and controls the advancement of the cell cycle by interacting with CDC25C.</div></div><div><h3>Conclusion</h3><div>Overall, our results support the novel regulatory role of SPDYE3 in LUSC cell cycle progression mechanisms by influencing the CDC25C/CDK1 signaling pathway.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"186 ","pages":"Article 106825"},"PeriodicalIF":3.4,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144517775","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":"27P silk bioactive peptides mediate multifaceted regulation of collagen and support balance in fibroblast subpopulations","authors":"SaiLavanyaa Sundar, Marios Frantzeskos Sardis, Lior Artzi, Aneesha Polisety, Setu Vora, Greg Altman, Svetlana Marukian","doi":"10.1016/j.biocel.2025.106821","DOIUrl":"10.1016/j.biocel.2025.106821","url":null,"abstract":"<div><div>Fibroblasts play a key role in maintaining skin structure and immune balance, but factors like aging, stress, and chronic inflammation can weaken their function, leading to collagen loss, thinning skin, and increased inflammation. Traditional collagen boosters like retinoic acid (RA), vitamin C (VC), hyaluronic acid (HA), and transforming growth factor beta (TGFβ) have drawbacks, including poor absorption, instability, and irritation.</div><div>Studies reveal that Silk Bioactive Peptide (27 P peptide) binds to epidermis and dermal fibroblasts, enhancing prolonged pro-collagen 1 (pro-C1) secretion in 3D and 2D models. <em>De-novo</em> collagen synthesis by 27 P peptide, likely regulated at the translational level, resulted in elevated collagen deposition and matrix remodeling up to 120 h. Combination of VC and 27 P peptide rescues VC-induced intracellular collagen depletion. Unlike TGFβ and RA, 27 P peptide maintains balance between fibroblast subpopulations, without inducing markers of fibrosis or inflammation. Together, 27 P peptide presents as a promising alternative to effectively promote collagen production, fibroblast homeostasis and skin health.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"186 ","pages":"Article 106821"},"PeriodicalIF":3.4,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340579","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}
Jie Lu , Zhuo Lv , Meizhu xue , Dan Fan , Huiping Yang , Yi Hong , Yichen Wang , Zhangqiang Guo , Jiajun Ma , Jie Huang , Lijun Meng , Shuiyan Wu , Zhenjiang Bai
{"title":"Sepsis impairs immunocompetent plasmacytoid dendritic cell reconstitution from hematopoietic stem/progenitor cell through altered bone marrow environment","authors":"Jie Lu , Zhuo Lv , Meizhu xue , Dan Fan , Huiping Yang , Yi Hong , Yichen Wang , Zhangqiang Guo , Jiajun Ma , Jie Huang , Lijun Meng , Shuiyan Wu , Zhenjiang Bai","doi":"10.1016/j.biocel.2025.106823","DOIUrl":"10.1016/j.biocel.2025.106823","url":null,"abstract":"<div><div>Plasmacytoid dendritic cells (pDCs) are crucial components of the immune response during viral infections, yet their function and development in the late phase of sepsis remain poorly understood. In this study, we investigated the impact of prolonged sepsis on pDCs and their progenitors in cecal ligation and puncture (CLP)-induced septic mice. We observed a significant reduction in both pDCs and their progenitors, alongside the presence of mature and regulatory pDCs. These mature and regulatory pDCs exhibited impaired type I interferon (IFN) secretion and antigen presentation capacity. In a Flt3L culture system of hematopoietic stem/progenitor cells (HSPCs) from CLP and Sham mice, we found that CLP-derived HSPCs exhibited an impaired ability to generate immunocompetent pDCs, as evidenced by lower IFN-α expression and reduced pDC recovery. Further investigation revealed downregulation of the key transcription factor TCF4 during pDC differentiation in these progenitor cells. Ectopic expression of TCF4 in these progenitors restored pDC generation. Additionally, we observed elevated levels of granulocyte colony-stimulating factor (G-CSF) in the bone marrow supernatant of septic mice. The addition of G-CSF to the culture system significantly impaired the generation of immunocompetent pDCs from HSPCs of normal mice. These findings suggest that sepsis may impair the production of immunocompetent pDCs from HSPCs by modulating key genes involved in pDC differentiation, potentially contributing to immune suppression and increased susceptibility to opportunistic infections in the later stages of sepsis.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"186 ","pages":"Article 106823"},"PeriodicalIF":3.4,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340580","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}
Sanyukta Rana, Christoph Claas, Cosima C Kretz, Irina Nazarenko, Margot Zoeller
{"title":"Retraction notice to \"Activation-induced internalization differs for the tetraspanins CD9 and Tspan8: Impact on tumor cell motility\" [Intern. J. Biochem. Cell Biol., 43/1 (2011) 106-119].","authors":"Sanyukta Rana, Christoph Claas, Cosima C Kretz, Irina Nazarenko, Margot Zoeller","doi":"10.1016/j.biocel.2025.106818","DOIUrl":"https://doi.org/10.1016/j.biocel.2025.106818","url":null,"abstract":"","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":" ","pages":"106818"},"PeriodicalIF":3.4,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318558","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}