Pub Date : 2025-08-15DOI: 10.1016/j.biocel.2025.106850
Shan Wang , Jiahao Huang , Fangping He , Jiaxiao Lin, Xinyu Zheng, Na Zhang, Ailin Tao
Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by a complex pathogenesis involving aberrant activation of multiple immune responses. In recent years, targeted biologics have demonstrated significant efficacy in treating moderate to severe AD due to their precise mechanisms. However, the complex inflammatory profile of AD poses challenges for single-target biologics, leading to suboptimal therapeutic responses. By investigating the upstream induction mechanisms of mixed immune endotypes of AD, our study examined the roles of three types of skin antigen-presenting cells (APCs) in inducing distinct inflammatory responses in AD pathogenesis, utilizing animal models and genetically deficient mice. Our findings revealed that epidermal Langerhans cells primarily recognize allergens, induce Th2 inflammation, and promote IgE production. Nlrp3 contributes to macrophage activation by the AD lesion microbiota, driving Th17 inflammation and IgG1 production. The STING pathway facilitates dendritic cell activation, exacerbates the overall inflammatory process across mixed immune endotypes of AD, and the production of IgG2a and IgG1. In summary, our study conducted a comprehensive analysis of the upstream key antigen-presenting cells and their regulatory pathways that contribute to the progression of AD-associated immune endotypes. This research provides valuable insights into upstream mechanisms for controlling AD mixed inflammatory processes and offers strategic directions for developing combination therapies targeting multiple inflammatory pathways.
{"title":"Antigen-presenting cells orchestrate mixed inflammatory endotypes in atopic dermatitis","authors":"Shan Wang , Jiahao Huang , Fangping He , Jiaxiao Lin, Xinyu Zheng, Na Zhang, Ailin Tao","doi":"10.1016/j.biocel.2025.106850","DOIUrl":"10.1016/j.biocel.2025.106850","url":null,"abstract":"<div><div>Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by a complex pathogenesis involving aberrant activation of multiple immune responses. In recent years, targeted biologics have demonstrated significant efficacy in treating moderate to severe AD due to their precise mechanisms. However, the complex inflammatory profile of AD poses challenges for single-target biologics, leading to suboptimal therapeutic responses. By investigating the upstream induction mechanisms of mixed immune endotypes of AD, our study examined the roles of three types of skin antigen-presenting cells (APCs) in inducing distinct inflammatory responses in AD pathogenesis, utilizing animal models and genetically deficient mice. Our findings revealed that epidermal Langerhans cells primarily recognize allergens, induce Th2 inflammation, and promote IgE production. Nlrp3 contributes to macrophage activation by the AD lesion microbiota, driving Th17 inflammation and IgG1 production. The STING pathway facilitates dendritic cell activation, exacerbates the overall inflammatory process across mixed immune endotypes of AD, and the production of IgG2a and IgG1. In summary, our study conducted a comprehensive analysis of the upstream key antigen-presenting cells and their regulatory pathways that contribute to the progression of AD-associated immune endotypes. This research provides valuable insights into upstream mechanisms for controlling AD mixed inflammatory processes and offers strategic directions for developing combination therapies targeting multiple inflammatory pathways.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"188 ","pages":"Article 106850"},"PeriodicalIF":2.8,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144876574","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}
Pub Date : 2025-08-05DOI: 10.1016/j.biocel.2025.106841
Lin Cheng , Ge Wu , Wei Yao , Kangrong Deng , Chunsun Zhang , Tongsheng Chen
The function of silencing information regulator 1 (SIRT1) in promoting or inhibiting apoptosis remains a subject of debate. Here, we aim to evaluate the roles of nuclear-localized SIRT1 in STS/DOX-induced apoptosis. Silencing nuclear-localized SIRT1 significantly enhanced STS/DOX-induced apoptosis, while overexpression of nuclear-localized SIRT1 markedly inhibited STS/DOX-induced process, demonstrating the anti-apoptotic ability of the nuclear-localized SIRT1. Critically, silencing p53 compromised the anti-apoptotic function of nuclear-localized SIRT1, thereby underscoring the essential role of p53 in mediating SIRT1's anti-apoptotic capability. Western blot analysis further revealed that wild-type SIRT1 robustly downregulated Ac-p53 expression to inhibit apoptosis, whereas a deacetylase-defective mutant of SIRT1 (SIRT1H363Y) markedly upregulated Ac-p53 to promote apoptosis. Fluorescence resonance energy transfer (FRET) analyses for the cells co-expressing nuclear-localized SIRT1-CFP and p53-YFP showed that STS enhanced the direct interaction between SIRT1 and p53 in nucleus, suggesting that the nuclear-localized SIRT1 directly interacts with p53 to deacetylate p53, thus inhibiting apoptosis. On the contrary，overexpression of cytoplasm-localized SIRT1 markedly promoted STS/DOX-induced apoptosis, firmly demonstrating the pro-apoptotic ability of the cytoplasm-localized SIRT1. These results firmly demonstrate a notion that nuclear-localized SIRT1 inhibits apoptosis via deacetylating p53.
{"title":"Nuclear-localized SIRT1 inhibits apoptosis via deacetylating p53","authors":"Lin Cheng , Ge Wu , Wei Yao , Kangrong Deng , Chunsun Zhang , Tongsheng Chen","doi":"10.1016/j.biocel.2025.106841","DOIUrl":"10.1016/j.biocel.2025.106841","url":null,"abstract":"<div><div>The function of silencing information regulator 1 (SIRT1) in promoting or inhibiting apoptosis remains a subject of debate. Here, we aim to evaluate the roles of nuclear-localized SIRT1 in STS/DOX-induced apoptosis. Silencing nuclear-localized SIRT1 significantly enhanced STS/DOX-induced apoptosis, while overexpression of nuclear-localized SIRT1 markedly inhibited STS/DOX-induced process, demonstrating the anti-apoptotic ability of the nuclear-localized SIRT1. Critically, silencing p53 compromised the anti-apoptotic function of nuclear-localized SIRT1, thereby underscoring the essential role of p53 in mediating SIRT1's anti-apoptotic capability. Western blot analysis further revealed that wild-type SIRT1 robustly downregulated Ac-p53 expression to inhibit apoptosis, whereas a deacetylase-defective mutant of SIRT1 (SIRT1<sup>H363Y</sup>) markedly upregulated Ac-p53 to promote apoptosis. Fluorescence resonance energy transfer (FRET) analyses for the cells co-expressing nuclear-localized SIRT1-CFP and p53-YFP showed that STS enhanced the direct interaction between SIRT1 and p53 in nucleus, suggesting that the nuclear-localized SIRT1 directly interacts with p53 to deacetylate p53, thus inhibiting apoptosis. On the contrary，overexpression of cytoplasm-localized SIRT1 markedly promoted STS/DOX-induced apoptosis, firmly demonstrating the pro-apoptotic ability of the cytoplasm-localized SIRT1. These results firmly demonstrate a notion that nuclear-localized SIRT1 inhibits apoptosis via deacetylating p53.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"187 ","pages":"Article 106841"},"PeriodicalIF":2.8,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144769237","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}
Pub Date : 2025-07-23DOI: 10.1016/j.biocel.2025.106840
Chengyang Sun , Mengying Jin , Ying Lian , Aodi Jiang , Hongfeng Zhai
Substrate stiffness is a critical biophysical cue regulating mesenchymal stem cell (MSC) fate, yet the underlying mechanisms remain incompletely understood. Here, we investigated how substrate stiffness modulates the osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs) and the involvement of the Hedgehog (Hh) signaling pathway in this process. Polydimethylsiloxane (PDMS) substrates with tunable stiffness (soft: 32.73 ± 3.74 kPa; medium: 57.59 ± 5.65 kPa; stiff: 147.4 ± 11.04 kPa) were fabricated and functionalized with arginine-glycine-aspartic acid (RGD) peptides to mimic the mechanical microenvironment of bone tissue. BMMSCs cultured on stiff substrates exhibited enhanced cell spreading and proliferation compared to those on soft substrates. Osteogenic induction experiments revealed that stiff substrates significantly upregulated alkaline phosphatase (ALP) expression and calcium nodule formation after 7 and 21 days, respectively. Mechanistically, the Hh pathway was activated on stiff substrates at day 3. Inhibition of Hh signaling using GANT61 impeded stiffness-induced effects, reducing cell spreading, proliferation, and osteogenic differentiation. These findings demonstrate that substrate stiffness promotes BMMSCs osteogenesis in a Hh signaling-dependent manner, providing new insights into the mechanobiology of bone regeneration and informing the design of stiffness-optimized biomaterials for tissue engineering applications.
{"title":"Substrate stiffness modulates osteogenic differentiation of BMMSCs via the hedgehog signaling pathway","authors":"Chengyang Sun , Mengying Jin , Ying Lian , Aodi Jiang , Hongfeng Zhai","doi":"10.1016/j.biocel.2025.106840","DOIUrl":"10.1016/j.biocel.2025.106840","url":null,"abstract":"<div><div>Substrate stiffness is a critical biophysical cue regulating mesenchymal stem cell (MSC) fate, yet the underlying mechanisms remain incompletely understood. Here, we investigated how substrate stiffness modulates the osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs) and the involvement of the Hedgehog (Hh) signaling pathway in this process. Polydimethylsiloxane (PDMS) substrates with tunable stiffness (soft: 32.73 ± 3.74 kPa; medium: 57.59 ± 5.65 kPa; stiff: 147.4 ± 11.04 kPa) were fabricated and functionalized with arginine-glycine-aspartic acid (RGD) peptides to mimic the mechanical microenvironment of bone tissue. BMMSCs cultured on stiff substrates exhibited enhanced cell spreading and proliferation compared to those on soft substrates. Osteogenic induction experiments revealed that stiff substrates significantly upregulated alkaline phosphatase (ALP) expression and calcium nodule formation after 7 and 21 days, respectively. Mechanistically, the Hh pathway was activated on stiff substrates at day 3. Inhibition of Hh signaling using GANT61 impeded stiffness-induced effects, reducing cell spreading, proliferation, and osteogenic differentiation. These findings demonstrate that substrate stiffness promotes BMMSCs osteogenesis in a Hh signaling-dependent manner, providing new insights into the mechanobiology of bone regeneration and informing the design of stiffness-optimized biomaterials for tissue engineering applications.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"187 ","pages":"Article 106840"},"PeriodicalIF":2.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718991","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}
Pub Date : 2025-07-12DOI: 10.1016/j.biocel.2025.106831
Xiaoyu Zheng, Bin Jiang, Yingchun Zhang, Shigao Ye, Yongchun Liu
Background
Among the many malignancies, lung adenocarcinoma (LUAD) is a top global health and life risk. The focus of this research is to explore how the TCF21/ERO1A pathway influences the immune escape mechanisms triggered by aerobic glycolysis in LUAD.
Methods
After downloading mRNA expression data from TCGA-LUAD and conducting differential expression analysis, we identified our target mRNA based on literature review. We used the hTFtarget database to forecast the upstream transcription factor (TF) of the target mRNA, and their binding relationship was verified through dual-luciferase experiments. Gene set enrichment analysis (GSEA) was performed on the target gene to probe its impact on LUAD-associated signaling pathways. qRT-PCR was used to detect the expression of ERO1A, TCF21, and PD-L1 mRNA. Western blot was employed to measure the expression levels of glycolysis-related proteins (SLC2A1, HK2, LDHA) and PD-L1 protein. Extracellular acidification rate and oxygen consumption rate were evaluated using a Seahorse metabolic analyzer. The apoptosis of CD8+ T cells and the activation status of CD8+ T cells were detected by flow cytometry. We also conducted 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay to assess the cytotoxicity of natural killer cells against LUAD cells.
Results
High expression levels of ERO1A were observed in LUAD tissues and cells. GSEA identified a notable association of ERO1A with glycolytic processes and tumor immune evasion pathways. The depletion of ERO1A deeply impaired the glycolytic capacity, immune evasion abilities, and PD-L1 expression in LUAD cells, as validated by both cellular and molecular experiments. ERO1A induced immune evasion in LUAD cells via the upregulation of PD-L1. TCF21, an upstream regulator of ERO1A, was found to be downregulated in LUAD. Dual-luciferase assays also provided evidence for the specific binding of ERO1A to TCF21. Recovery experiments showed TCF21 curbed the stimulatory effect of glycolysis on the immune evasion of LUAD cells by suppressing ERO1A expression.
Conclusion
TCF21 directs its action towards ERO1A, thereby inhibiting the glycolysis-mediated promotion of immune evasion in LUAD cells. As such, the TCF21/ERO1A axis could be harnessed as a therapeutic target and a prognosis marker in LUAD.
{"title":"Inhibition of ERO1A by TCF21 curbs aerobic glycolysis and enhances immune recognition in lung adenocarcinoma","authors":"Xiaoyu Zheng, Bin Jiang, Yingchun Zhang, Shigao Ye, Yongchun Liu","doi":"10.1016/j.biocel.2025.106831","DOIUrl":"10.1016/j.biocel.2025.106831","url":null,"abstract":"<div><h3>Background</h3><div>Among the many malignancies, lung adenocarcinoma (LUAD) is a top global health and life risk. The focus of this research is to explore how the TCF21/ERO1A pathway influences the immune escape mechanisms triggered by aerobic glycolysis in LUAD.</div></div><div><h3>Methods</h3><div>After downloading mRNA expression data from TCGA-LUAD and conducting differential expression analysis, we identified our target mRNA based on literature review. We used the hTFtarget database to forecast the upstream transcription factor (TF) of the target mRNA, and their binding relationship was verified through dual-luciferase experiments. Gene set enrichment analysis (GSEA) was performed on the target gene to probe its impact on LUAD-associated signaling pathways. qRT-PCR was used to detect the expression of ERO1A, TCF21, and PD-L1 mRNA. Western blot was employed to measure the expression levels of glycolysis-related proteins (SLC2A1, HK2, LDHA) and PD-L1 protein. Extracellular acidification rate and oxygen consumption rate were evaluated using a Seahorse metabolic analyzer. The apoptosis of CD8<sup>+</sup> T cells and the activation status of CD8<sup>+</sup> T cells were detected by flow cytometry. We also conducted 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay to assess the cytotoxicity of natural killer cells against LUAD cells.</div></div><div><h3>Results</h3><div>High expression levels of ERO1A were observed in LUAD tissues and cells. GSEA identified a notable association of ERO1A with glycolytic processes and tumor immune evasion pathways. The depletion of ERO1A deeply impaired the glycolytic capacity, immune evasion abilities, and PD-L1 expression in LUAD cells, as validated by both cellular and molecular experiments. ERO1A induced immune evasion in LUAD cells via the upregulation of PD-L1. TCF21, an upstream regulator of ERO1A, was found to be downregulated in LUAD. Dual-luciferase assays also provided evidence for the specific binding of ERO1A to TCF21. Recovery experiments showed TCF21 curbed the stimulatory effect of glycolysis on the immune evasion of LUAD cells by suppressing ERO1A expression.</div></div><div><h3>Conclusion</h3><div>TCF21 directs its action towards ERO1A, thereby inhibiting the glycolysis-mediated promotion of immune evasion in LUAD cells. As such, the TCF21/ERO1A axis could be harnessed as a therapeutic target and a prognosis marker in LUAD.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"187 ","pages":"Article 106831"},"PeriodicalIF":2.8,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144638591","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}
Pub Date : 2025-07-05DOI: 10.1016/j.biocel.2025.106830
Yubing Liu , Vidhi Pareek , Dipankar Bhowmik , Xin Zhang , Stephen J. Benkovic
Purines are the building blocks of DNA/RNA and hence essential metabolites. While the contributions of external purine salvage as well as the de novo 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.
{"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}
Pub Date : 2025-07-03DOI: 10.1016/j.biocel.2025.106828
Rui Zhou, Xiuzhu Wang, Nannan Li
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 in vivo. 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 in vitro, human cardiomyocytes AC16 cells were treated with high glucose (HG), and results obtained in vitro were consistent with those in vivo. 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.
{"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}
Pub Date : 2025-07-03DOI: 10.1016/j.biocel.2025.106827
Amrutha Arjunan , Ganesh Venkatraman , Leena Dennis Joseph , Lakshmi R. Perumalsamy
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.
{"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}
Pub Date : 2025-07-01DOI: 10.1016/j.biocel.2025.106826
Ashira Manzoor, Khaled Barakat
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.
{"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}
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