The chemokine signaling pathway is a key factor in inflammation and the development of diabetic nephropathy (DN). The involvement of RNA-binding proteins (RBPs) in modulating this pathway is not yet fully clarified. This study aimed to examine the regulatory role of RBPs in the chemokine signaling pathway associated with DN. Using transcriptional data from the GSE142153 dataset, DEGs were identified. By intersecting DN-associated DEGs with chemokine pathway genes from the MSigDB database, 30 common genes were identified. Four hub genes were then selected through PPI network analysis. Target RBPs of these hub genes were predicted using the RNAInter database, with ELAVL1 identified as a shared regulatory RBP. The expression of ELAVL1 was further validated in the GSE142025 dataset. ELAVL1 gene expression was measured in 90 PBMC samples from three groups: T2D patients, DN patients, and healthy controls, with 30 individuals in each group. Real-time PCR results demonstrated a significant upregulation of ELAVL1 in DN patients versus T2D and control groups. This study highlights the critical role of ELAVL1 in promoting inflammation through the chemokine signaling pathway and contributing to renal injury. Thus, ELAVL1 could be considered a valuable biomarker for identifying and tracking the development of DN.
{"title":"Unveiling ELAVL1 as a key RNA-binding protein regulating the chemokine signaling pathway in diabetic nephropathy","authors":"Seyed Amirhossein Hosseini , Parisa Ajorlou , Ali Bandsariyan , Shahla Sohrabipour","doi":"10.1016/j.bbrep.2025.102391","DOIUrl":"10.1016/j.bbrep.2025.102391","url":null,"abstract":"<div><div>The chemokine signaling pathway is a key factor in inflammation and the development of diabetic nephropathy (DN). The involvement of RNA-binding proteins (RBPs) in modulating this pathway is not yet fully clarified. This study aimed to examine the regulatory role of RBPs in the chemokine signaling pathway associated with DN. Using transcriptional data from the GSE142153 dataset, DEGs were identified. By intersecting DN-associated DEGs with chemokine pathway genes from the MSigDB database, 30 common genes were identified. Four hub genes were then selected through PPI network analysis. Target RBPs of these hub genes were predicted using the RNAInter database, with ELAVL1 identified as a shared regulatory RBP. The expression of ELAVL1 was further validated in the GSE142025 dataset. ELAVL1 gene expression was measured in 90 PBMC samples from three groups: T2D patients, DN patients, and healthy controls, with 30 individuals in each group. Real-time PCR results demonstrated a significant upregulation of ELAVL1 in DN patients versus T2D and control groups. This study highlights the critical role of ELAVL1 in promoting inflammation through the chemokine signaling pathway and contributing to renal injury. Thus, ELAVL1 could be considered a valuable biomarker for identifying and tracking the development of DN.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102391"},"PeriodicalIF":2.2,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145691635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.bbrep.2025.102364
Jingjing Ge , Cheng Li , Fengjun Xue , Chi Zhao , Chenchen Kong , Shaopei Qi , Qianqian Duan , Qin Zhang , Junping Zhang
Apatinib in combination with temozolomide (TMZ) has achieved reasonable clinical efficacy in the treatment of recurrent glioblastoma (rGBM), however, there are currently no clear biomarkers related to clinical efficacy or prognosis. Our retrospective study was to investigate tumor microenvironment (TME) features at the gene expression level that are associated with response and long survival benefit of rGBM treated with apatinib and TMZ. We enrolled 22 rGBMs treated with apatinib in combination with TMZ and collected their tissue samples for RNA transcriptome analysis by the Nanostring nCounter platform. The response group had 40 differentially expressed genes compared to the non-response group, with significantly up-regulated expression of genes related to endothelial cells and apoptosis. Enrichment analysis revealed that signaling pathways related to cell proliferation were down-regulated in the response group. In terms of prognosis, there were 16 differential expressed genes in the long-survival benefit group compared with the short-survival benefit group, and four tumor progression-associated genes were also down-regulated in response group expression. Hypoxia related-genes was significantly up-regulated in the long survival benefit group. Enrichment analysis showed that genes related to cell proliferation were also down-regulated in the long-survival benefit group, while the expression of signaling pathway genes related to cell activation, and immune response was significantly up-regulated. Our study suggests that the combination of apatinib and TMZ may potentially provide clinical benefits in treating rGBM by modulating genes associated with cell proliferation, promoting apoptosis, regulating hypoxia, and enhancing immune response within the tumor microenvironment.
{"title":"Alterations of the tumor microenvironment (TME) by exploratory gene expression analysis in recurrent glioblastoma following apatinib in combination with temozolomide","authors":"Jingjing Ge , Cheng Li , Fengjun Xue , Chi Zhao , Chenchen Kong , Shaopei Qi , Qianqian Duan , Qin Zhang , Junping Zhang","doi":"10.1016/j.bbrep.2025.102364","DOIUrl":"10.1016/j.bbrep.2025.102364","url":null,"abstract":"<div><div>Apatinib in combination with temozolomide (TMZ) has achieved reasonable clinical efficacy in the treatment of recurrent glioblastoma (rGBM), however, there are currently no clear biomarkers related to clinical efficacy or prognosis. Our retrospective study was to investigate tumor microenvironment (TME) features at the gene expression level that are associated with response and long survival benefit of rGBM treated with apatinib and TMZ. We enrolled 22 rGBMs treated with apatinib in combination with TMZ and collected their tissue samples for RNA transcriptome analysis by the Nanostring nCounter platform. The response group had 40 differentially expressed genes compared to the non-response group, with significantly up-regulated expression of genes related to endothelial cells and apoptosis. Enrichment analysis revealed that signaling pathways related to cell proliferation were down-regulated in the response group. In terms of prognosis, there were 16 differential expressed genes in the long-survival benefit group compared with the short-survival benefit group, and four tumor progression-associated genes were also down-regulated in response group expression. Hypoxia related-genes was significantly up-regulated in the long survival benefit group. Enrichment analysis showed that genes related to cell proliferation were also down-regulated in the long-survival benefit group, while the expression of signaling pathway genes related to cell activation, and immune response was significantly up-regulated. Our study suggests that the combination of apatinib and TMZ may potentially provide clinical benefits in treating rGBM by modulating genes associated with cell proliferation, promoting apoptosis, regulating hypoxia, and enhancing immune response within the tumor microenvironment.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102364"},"PeriodicalIF":2.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145691634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.bbrep.2025.102382
Amir Hossein Mohammadi , Parvin Yavari
Due to numerous overlapping risk factors between cardiovascular diseases (CVDs) and infertility, women of reproductive age with underlying CVD may increasingly seek reproductive assistance. miRNAs and exosomal miRNAs are well-known epigenetic modulators that regulate gene expression at the post-transcriptional level. A large body of evidence indicates the fundamental roles of various miRNAs in different aspects of both CVD and infertility. Dysregulation of miRNAs (including those carried by exosomes) could contribute to pathological alterations involved in CVD pathogenesis, potentially leading to female infertility-related disorders In particular, we emphasize how these miRNAs shape inflammatory, angiogenic and remodeling responses in the injured myocardium of infertile women. Herein, we review the roles of miRNAs in the development of CVD and female infertility. We also summarize recent research on the role of miRNAs in angiogenesis, including their targets and mechanisms of action. Understanding these mechanisms may facilitate the development of composite biomarkers and targeted diagnostic/therapeutic strategies for female infertility and cardiovascular disease, with a specific focus on myocardial injury.
{"title":"What role do miRNAs play in the injured heart of the infertile female?","authors":"Amir Hossein Mohammadi , Parvin Yavari","doi":"10.1016/j.bbrep.2025.102382","DOIUrl":"10.1016/j.bbrep.2025.102382","url":null,"abstract":"<div><div>Due to numerous overlapping risk factors between cardiovascular diseases (CVDs) and infertility, women of reproductive age with underlying CVD may increasingly seek reproductive assistance. miRNAs and exosomal miRNAs are well-known epigenetic modulators that regulate gene expression at the post-transcriptional level. A large body of evidence indicates the fundamental roles of various miRNAs in different aspects of both CVD and infertility. Dysregulation of miRNAs (including those carried by exosomes) could contribute to pathological alterations involved in CVD pathogenesis, potentially leading to female infertility-related disorders In particular, we emphasize how these miRNAs shape inflammatory, angiogenic and remodeling responses in the injured myocardium of infertile women. Herein, we review the roles of miRNAs in the development of CVD and female infertility. We also summarize recent research on the role of miRNAs in angiogenesis, including their targets and mechanisms of action. Understanding these mechanisms may facilitate the development of composite biomarkers and targeted diagnostic/therapeutic strategies for female infertility and cardiovascular disease, with a specific focus on myocardial injury.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"44 ","pages":"Article 102382"},"PeriodicalIF":2.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145620485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-29DOI: 10.1016/j.bbrep.2025.102359
Jihao Shi, Lexi Wu, Chuwen Tian, Haotian Chen
Colorectal cancer (CRC) ranks among the most prevalent malignancies globally and is the third leading cause of cancer - related deaths. Despite advancements in diagnosis and treatment, prognosis for CRC patients, especially those with advanced or metastatic disease, remains difficult due to its heterogeneity. Mitochondria, central to cellular activity, and the mitochondrial unfolded protein response (UPRmt), a stress - responsive pathway, are involved in various physiological and pathological processes. Recent studies have emphasized the importance of UPRmt in cancer biology. In this research, we explored the role of UPR - related genes (MRGs) in CRC. Through analyzing transcriptional profiles and clinical data of CRC patients, we identified different molecular subtypes according to MRG expression, which were related to patient prognosis, immune cell infiltration, and drug sensitivity. We also developed a prognostic signature based on key MRGs with strong predictive power for patient survival and treatment response. Additionally, the study of the spatial distribution of MRGs in tumor tissues revealed their heterogeneous expression and potential influence on tumor biology. Overall, our findings clarify the role of UPR in CRC and highlight its potential as a target for personalized cancer therapy.
{"title":"Unraveling the role of mitochondrial unfolded protein response in colorectal cancer","authors":"Jihao Shi, Lexi Wu, Chuwen Tian, Haotian Chen","doi":"10.1016/j.bbrep.2025.102359","DOIUrl":"10.1016/j.bbrep.2025.102359","url":null,"abstract":"<div><div>Colorectal cancer (CRC) ranks among the most prevalent malignancies globally and is the third leading cause of cancer - related deaths. Despite advancements in diagnosis and treatment, prognosis for CRC patients, especially those with advanced or metastatic disease, remains difficult due to its heterogeneity. Mitochondria, central to cellular activity, and the mitochondrial unfolded protein response (UPR<sup>mt</sup>), a stress - responsive pathway, are involved in various physiological and pathological processes. Recent studies have emphasized the importance of UPR<sup>mt</sup> in cancer biology. In this research, we explored the role of UPR - related genes (MRGs) in CRC. Through analyzing transcriptional profiles and clinical data of CRC patients, we identified different molecular subtypes according to MRG expression, which were related to patient prognosis, immune cell infiltration, and drug sensitivity. We also developed a prognostic signature based on key MRGs with strong predictive power for patient survival and treatment response. Additionally, the study of the spatial distribution of MRGs in tumor tissues revealed their heterogeneous expression and potential influence on tumor biology. Overall, our findings clarify the role of UPR in CRC and highlight its potential as a target for personalized cancer therapy.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102359"},"PeriodicalIF":2.2,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145622884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-29DOI: 10.1016/j.bbrep.2025.102389
Priyanka Sharma, Mohd Suleman, Niti Puri
Erythrocytes are exposed to reactive oxygen species during circulation constantly, due to normal aerobic cellular metabolism and pathology of inflammatory diseases. Genetic depletion of mast cells and systemic mastocytosis seem to affect anaemia. We attempted to reveal the participation of mast cells in erythrocytes clearance in vivo and during interaction with professional phagocytes like macrophages in vitro. Mastocytosis was induced in DBA/2 mice by injecting P815 cells and mast cell depletion was attained with compound 48/80 treatment under normal or phenylhydrazine (PHZ) induced oxidative stress conditions in mice. The mastocytosis model showed a significant decrease in circulatory erythrocytes while mast cell absence led to significantly high accumulation of erythrocytes in spleens of mast cell depleted anemic mice. The present study provides important evidences for contribution of mast cells in erythrocyte clearance during oxidative stress conditions and augmented uptake of oxydatively damaged erythrocytes (ODE) in presence of macrophages in close proximity.
{"title":"New insight into role of mast cells in erythrocyte homeostasis and clearance under oxidative stress conditions in vivo","authors":"Priyanka Sharma, Mohd Suleman, Niti Puri","doi":"10.1016/j.bbrep.2025.102389","DOIUrl":"10.1016/j.bbrep.2025.102389","url":null,"abstract":"<div><div>Erythrocytes are exposed to reactive oxygen species during circulation constantly, due to normal aerobic cellular metabolism and pathology of inflammatory diseases. Genetic depletion of mast cells and systemic mastocytosis seem to affect anaemia. We attempted to reveal the participation of mast cells in erythrocytes clearance <em>in vivo</em> and during interaction with professional phagocytes like macrophages <em>in vitro</em>. Mastocytosis was induced in DBA/2 mice by injecting P815 cells and mast cell depletion was attained with compound 48/80 treatment under normal or phenylhydrazine (PHZ) induced oxidative stress conditions in mice. The mastocytosis model showed a significant decrease in circulatory erythrocytes while mast cell absence led to significantly high accumulation of erythrocytes in spleens of mast cell depleted anemic mice. The present study provides important evidences for contribution of mast cells in erythrocyte clearance during oxidative stress conditions and augmented uptake of oxydatively damaged erythrocytes (ODE) in presence of macrophages in close proximity.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102389"},"PeriodicalIF":2.2,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145622885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-28DOI: 10.1016/j.bbrep.2025.102375
Franz Müller , Sonja Neuser , Gaurav Shrestha , Netra P. Neupane , Katharina J. Götze , Nicola Brunetti-Pierri , Gaetano Terrone , Alexandre Reymond , Koen L. van Gassen , Eva Brilstra , Katharina Steindl , Anais Begemann , Anita Rauch , Jonathan Rips , Duha Fahham , Tahsin Stefan Barakat , Olivier Patat , Jérémie Mortreux , Matthew Hoi Kin Chau , Jill A. Rosenfeld , Dmitrij Ljaschenko
UNC13s are presynaptic proteins essential for neurotransmitter release at chemical synapses. In this study, we present eleven patients from nine families with severe neurodevelopmental impairments, who carry rare, biallelic UNC13C single-nucleotide variants (SNVs). Six missense variants, each identified in compound heterozygosity in one of three of these patients, were introduced into the Drosophila melanogaster ortholog unc13 using a previously established CRISPR/Cas9-based method for rapid and scarless genomic modifications, hypothesising that they underlie the observed clinical manifestations. However, none of the introduced mutations influenced Mendelian ratios, negative geotaxis, or lifespan of the fruit flies. Interestingly, two variants located outside the gene regions encoding known UNC13C domains caused a decreased ethanol sensitivity in Drosophila, while the Thr1729Met substitution within the C1 domain resulted in increased ethanol sensitivity. Molecular dynamics simulations of the latter mutant gene product suggested that the altered protein conformation enhances exposure of the ethanol-binding site, thereby increasing sensitivity to ethanol. These findings reinforce previous evidence highlighting the critical role of the C1 domain in ethanol sensitivity. Given the involvement of the C1 domain in synaptic plasticity this result might implicate an influence of the Thr1729Met on synaptic function.
{"title":"Single nucleotide variants in UNC13C associated with neurodevelopmental disorders affect ethanol sensitivity in Drosophila","authors":"Franz Müller , Sonja Neuser , Gaurav Shrestha , Netra P. Neupane , Katharina J. Götze , Nicola Brunetti-Pierri , Gaetano Terrone , Alexandre Reymond , Koen L. van Gassen , Eva Brilstra , Katharina Steindl , Anais Begemann , Anita Rauch , Jonathan Rips , Duha Fahham , Tahsin Stefan Barakat , Olivier Patat , Jérémie Mortreux , Matthew Hoi Kin Chau , Jill A. Rosenfeld , Dmitrij Ljaschenko","doi":"10.1016/j.bbrep.2025.102375","DOIUrl":"10.1016/j.bbrep.2025.102375","url":null,"abstract":"<div><div>UNC13s are presynaptic proteins essential for neurotransmitter release at chemical synapses. In this study, we present eleven patients from nine families with severe neurodevelopmental impairments, who carry rare, biallelic <em>UNC13C</em> single-nucleotide variants (SNVs). Six missense variants, each identified in compound heterozygosity in one of three of these patients, were introduced into the <em>Drosophila melanogaster</em> ortholog <em>unc13</em> using a previously established CRISPR/Cas9-based method for rapid and scarless genomic modifications, hypothesising that they underlie the observed clinical manifestations. However, none of the introduced mutations influenced Mendelian ratios, negative geotaxis, or lifespan of the fruit flies. Interestingly, two variants located outside the gene regions encoding known UNC13C domains caused a decreased ethanol sensitivity in <em>Drosophila</em>, while the Thr1729Met substitution within the C<sub>1</sub> domain resulted in increased ethanol sensitivity. Molecular dynamics simulations of the latter mutant gene product suggested that the altered protein conformation enhances exposure of the ethanol-binding site, thereby increasing sensitivity to ethanol. These findings reinforce previous evidence highlighting the critical role of the C<sub>1</sub> domain in ethanol sensitivity. Given the involvement of the C<sub>1</sub> domain in synaptic plasticity this result might implicate an influence of the Thr1729Met on synaptic function.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102375"},"PeriodicalIF":2.2,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145622782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-28DOI: 10.1016/j.bbrep.2025.102386
Zhong Zhou , Xulong Huang , Chaohang Chen , Tao Zou , Yifan Hai , Guokai Dong , Shanshan Li
Background and objective
Scarring presents a significant clinical challenge, imposing both physical and psychological burdens on patients. This drives the need for novel therapeutic strategies. Long non-coding RNAs (lncRNAs) have emerged as pivotal regulators of fibrosis. This study aims to investigate the role of the lncRNA RMST, which we identified as being upregulated during skin wound healing, in the pathogenesis of cutaneous scarring.
Materials and methods
A transcriptomic dataset was analyzed to identify lncRNAs dysregulated during skin wound healing. The function of RMST was assessed using in vivo RMST knockout models in a murine skin wound healing model. Wound tissues were harvested at day 21 post-injury for histological and molecular analysis. Downstream targets of RMST were predicted through bioinformatic analysis and validated using quantitative RT-PCR and Western blot. Finally, a rescue experiment was performed by overexpressing Smad3 in the context of RMST knockout to confirm the functional hierarchy.
Results
RMST knockout significantly suppressed fibrotic progression and inflammatory activity at day 21 post-injury, demonstrated by reduced collagen deposition and lower levels of key inflammatory mediators. Bioinformatic and experimental analyses identified Smad3 as a key downstream target. RMST knockout directly reduced both Smad3 mRNA and protein levels, indicating a direct regulatory mechanism acting at the expression level. Crucially, the anti-fibrotic effects of RMST knockout were effectively reversed upon Smad3 overexpression, confirming that Smad3 acts functionally downstream of RMST.
Conclusion
Our findings establish lncRNA RMST as a key driver of cutaneous fibrosis through its regulation of Smad3 expression. Targeting the RMST-Smad3 signaling axis therefore represents a promising therapeutic strategy for the treatment and prevention of scarring.
{"title":"LncRNA RMST knockout inhibits fibrosis by down-regulating Smad3 during mouse skin wound healing","authors":"Zhong Zhou , Xulong Huang , Chaohang Chen , Tao Zou , Yifan Hai , Guokai Dong , Shanshan Li","doi":"10.1016/j.bbrep.2025.102386","DOIUrl":"10.1016/j.bbrep.2025.102386","url":null,"abstract":"<div><h3>Background and objective</h3><div>Scarring presents a significant clinical challenge, imposing both physical and psychological burdens on patients. This drives the need for novel therapeutic strategies. Long non-coding RNAs (lncRNAs) have emerged as pivotal regulators of fibrosis. This study aims to investigate the role of the lncRNA RMST, which we identified as being upregulated during skin wound healing, in the pathogenesis of cutaneous scarring.</div></div><div><h3>Materials and methods</h3><div>A transcriptomic dataset was analyzed to identify lncRNAs dysregulated during skin wound healing. The function of RMST was assessed using in vivo RMST knockout models in a murine skin wound healing model. Wound tissues were harvested at day 21 post-injury for histological and molecular analysis. Downstream targets of RMST were predicted through bioinformatic analysis and validated using quantitative RT-PCR and Western blot. Finally, a rescue experiment was performed by overexpressing Smad3 in the context of RMST knockout to confirm the functional hierarchy.</div></div><div><h3>Results</h3><div>RMST knockout significantly suppressed fibrotic progression and inflammatory activity at day 21 post-injury, demonstrated by reduced collagen deposition and lower levels of key inflammatory mediators. Bioinformatic and experimental analyses identified Smad3 as a key downstream target. RMST knockout directly reduced both Smad3 mRNA and protein levels, indicating a direct regulatory mechanism acting at the expression level. Crucially, the anti-fibrotic effects of RMST knockout were effectively reversed upon Smad3 overexpression, confirming that Smad3 acts functionally downstream of RMST.</div></div><div><h3>Conclusion</h3><div>Our findings establish lncRNA RMST as a key driver of cutaneous fibrosis through its regulation of Smad3 expression. Targeting the RMST-Smad3 signaling axis therefore represents a promising therapeutic strategy for the treatment and prevention of scarring.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102386"},"PeriodicalIF":2.2,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145622784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Clear cell renal cell carcinoma (ccRCC) is the most prevalent subtype of renal malignancies, distinguished by its aggressive nature and poor prognosis in advanced stages. Identifying prognostic biomarkers and unraveling underlying molecular events contributing to ccRCC pathogenesis is crucial for developing precise prognostic models and tailored therapeutic interventions. The objective of this research was to identify differentially expressed genes (DEGs), construct protein-protein interaction networks, pinpoint hub genes and enriched pathways, assess the prognostic relevance of these hub genes, and predict upstream regulators, thereby providing insights into the onset and progression of ccRCC.
Methods
The GSE66270 dataset was reanalyzed to uncover DEGs between 14 ccRCC tumors and 14 normal tissues. Hub genes, clusters, and enriched functional categories were identified from the protein-protein interaction network. Survival analysis was performed to assess the prognostic relevance of the identified hub genes. An upstream transcription factor network was generated using the iRegulon plugin. Expression of hub genes in six cancer and six normal renal tissues was confirmed via real-time PCR.
Results
A prognostic signature comprising five genes—FCGR1A, FOXM1, TOP2A, BIRC5, and CCNA2—effectively stratified ccRCC prognosis. FOXM1 was identified as the primary upstream regulator. A significant upregulation of FOXM1 was observed in renal cancer samples compared with normal renal tissues (p-value <0.001).
Conclusion
These findings shed light on implicated pathways and processes, prognostic biomarkers, and the crucial role of the immune system in ccRCC pathogenesis.
{"title":"Unraveling the molecular landscape of clear cell renal cell carcinoma through integrative transcriptomic analysis and validation using clinical samples","authors":"Amir Taherkhani , Simindokht Sarvmeili , Hamed Manoochehri , Mahmoud Gholyaf","doi":"10.1016/j.bbrep.2025.102384","DOIUrl":"10.1016/j.bbrep.2025.102384","url":null,"abstract":"<div><h3>Background and aims</h3><div>Clear cell renal cell carcinoma (ccRCC) is the most prevalent subtype of renal malignancies, distinguished by its aggressive nature and poor prognosis in advanced stages. Identifying prognostic biomarkers and unraveling underlying molecular events contributing to ccRCC pathogenesis is crucial for developing precise prognostic models and tailored therapeutic interventions. The objective of this research was to identify differentially expressed genes (DEGs), construct protein-protein interaction networks, pinpoint hub genes and enriched pathways, assess the prognostic relevance of these hub genes, and predict upstream regulators, thereby providing insights into the onset and progression of ccRCC.</div></div><div><h3>Methods</h3><div>The GSE66270 dataset was reanalyzed to uncover DEGs between 14 ccRCC tumors and 14 normal tissues. Hub genes, clusters, and enriched functional categories were identified from the protein-protein interaction network. Survival analysis was performed to assess the prognostic relevance of the identified hub genes. An upstream transcription factor network was generated using the iRegulon plugin. Expression of hub genes in six cancer and six normal renal tissues was confirmed via real-time PCR.</div></div><div><h3>Results</h3><div>A prognostic signature comprising five genes—<em>FCGR1A</em>, <em>FOXM1</em>, <em>TOP2A</em>, <em>BIRC5</em>, and <em>CCNA2</em>—effectively stratified ccRCC prognosis. <em>FOXM1</em> was identified as the primary upstream regulator. A significant upregulation of <em>FOXM1</em> was observed in renal cancer samples compared with normal renal tissues (p-value <0.001).</div></div><div><h3>Conclusion</h3><div>These findings shed light on implicated pathways and processes, prognostic biomarkers, and the crucial role of the immune system in ccRCC pathogenesis.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102384"},"PeriodicalIF":2.2,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145622886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-27DOI: 10.1016/j.bbrep.2025.102387
Chenyang Wang , Xiaoshan Li , Changbing Wang , Yudan Ye , Mingqi Zhao , Min Guo , Tiantian Xu , Lu Kuang , Yuqing Yan , Wanli Liang , Xingui Tian , Bing Zhu
Severe adenovirus infections pose significant health challenges, particularly in immunocompromised individuals. This study characterizes the antiviral activity of dihydro-resveratrol (Dihydro-R) against adenovirus type 7 and reveals a SIRT1-dependent mechanism. Our study reveals that Dihydro-R effectively inhibits adenoviral replication across multiple cell lines through SIRT1 activation. Mechanistically, Dihydro-R suppresses the NF-κB and JAK/STAT pathways, leading to reduced expression of inflammatory factors. The critical role of SIRT1 in Dihydro-R's antiviral activity was confirmed through reverse validation using a SIRT1 inhibitor. Notably, Dihydro-R's antiviral effects correlate with SIRT1 upregulation, with A549 cells showing the strongest response. Time-course analysis demonstrates maximal inhibition of NF-κB and JAK/STAT pathways within 48 h of Dihydro-R treatment. Furthermore, Dihydro-R modulates the expression of key cytokines, including IL-8, IL-6, and IL-4, contributing to its anti-inflammatory properties. Our findings not only highlight Dihydro-R as a promising therapeutic candidate for adenovirus infections but also provide insights into SIRT1-targeted antiviral strategies. This study opens new avenues for developing natural compound-based therapies against adenoviral infections and potentially other viral diseases involving similar pathways.
{"title":"Dihydro-R demonstrates innate immunity against Adenovirus-7 by suppressing the NF-κB/JAK-STAT pathway in a SIRT1-dependent manner","authors":"Chenyang Wang , Xiaoshan Li , Changbing Wang , Yudan Ye , Mingqi Zhao , Min Guo , Tiantian Xu , Lu Kuang , Yuqing Yan , Wanli Liang , Xingui Tian , Bing Zhu","doi":"10.1016/j.bbrep.2025.102387","DOIUrl":"10.1016/j.bbrep.2025.102387","url":null,"abstract":"<div><div>Severe adenovirus infections pose significant health challenges, particularly in immunocompromised individuals. This study characterizes the antiviral activity of dihydro-resveratrol (Dihydro-R) against adenovirus type 7 and reveals a SIRT1-dependent mechanism. Our study reveals that Dihydro-R effectively inhibits adenoviral replication across multiple cell lines through SIRT1 activation. Mechanistically, Dihydro-R suppresses the NF-κB and JAK/STAT pathways, leading to reduced expression of inflammatory factors. The critical role of SIRT1 in Dihydro-R's antiviral activity was confirmed through reverse validation using a SIRT1 inhibitor. Notably, Dihydro-R's antiviral effects correlate with SIRT1 upregulation, with A549 cells showing the strongest response. Time-course analysis demonstrates maximal inhibition of NF-κB and JAK/STAT pathways within 48 h of Dihydro-R treatment. Furthermore, Dihydro-R modulates the expression of key cytokines, including IL-8, IL-6, and IL-4, contributing to its anti-inflammatory properties. Our findings not only highlight Dihydro-R as a promising therapeutic candidate for adenovirus infections but also provide insights into SIRT1-targeted antiviral strategies. This study opens new avenues for developing natural compound-based therapies against adenoviral infections and potentially other viral diseases involving similar pathways.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102387"},"PeriodicalIF":2.2,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145622783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-26DOI: 10.1016/j.bbrep.2025.102378
Amir masoud zarasvandi , Mohammad Gerayeli , Mina Abasi , Mehdi Goodarzi , Shabnam Ganjehzadeh , Raheleh solhmirzaei , Asieh Mozaffari , Haniyeh Alavi Milani
Periodontitis is a common chronic inflammatory disease that frequently results in tooth loss and systemic complications. Traditional diagnostic methods have limited sensitivity and often fail to detect early disease activity. Biosensors have emerged as promising tools for the early and accurate detection of specific biomarkers in saliva and gingival crevicular fluid. This review highlights recent advancements in electrochemical, optical, lab-on-a-chip technologies, and nanosensors for periodontal diagnosis. These innovations provide rapid, non-invasive, point-of-care capabilities, enabling improved monitoring and personalized treatment. While challenges remain in clinical translation, biosensors have significant potential to transform periodontal diagnostics and enhance patient outcomes.
{"title":"Electrochemical and optical biosensors for periodontitis detection","authors":"Amir masoud zarasvandi , Mohammad Gerayeli , Mina Abasi , Mehdi Goodarzi , Shabnam Ganjehzadeh , Raheleh solhmirzaei , Asieh Mozaffari , Haniyeh Alavi Milani","doi":"10.1016/j.bbrep.2025.102378","DOIUrl":"10.1016/j.bbrep.2025.102378","url":null,"abstract":"<div><div>Periodontitis is a common chronic inflammatory disease that frequently results in tooth loss and systemic complications. Traditional diagnostic methods have limited sensitivity and often fail to detect early disease activity. Biosensors have emerged as promising tools for the early and accurate detection of specific biomarkers in saliva and gingival crevicular fluid. This review highlights recent advancements in electrochemical, optical, lab-on-a-chip technologies, and nanosensors for periodontal diagnosis. These innovations provide rapid, non-invasive, point-of-care capabilities, enabling improved monitoring and personalized treatment. While challenges remain in clinical translation, biosensors have significant potential to transform periodontal diagnostics and enhance patient outcomes.</div></div><div><h3>Clinical trial number</h3><div>not applicable.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102378"},"PeriodicalIF":2.2,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145594589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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