Pub Date : 2026-01-21DOI: 10.1016/j.bbrc.2026.153323
Yu Zhou , Bohao Zhao , Shaoning Sun , Xiaoman Han , Yongqi Yu , Jinbao Li , Yang Chen , Xinsheng Wu
Hair follicle (HF) morphogenesis, growth, and regeneration are fundamentally governed by reciprocal interactions between the epidermal and dermal compartments of the skin, with dermal papilla cells (DPCs) serving as a central regulatory element in this process. Here, the functional role of Toll-like receptor 2 (TLR2) in the control of DPC proliferation was investigated. The coding sequence (CDS) of the rabbit TLR2 gene was successfully cloned and subjected to preliminary bioinformatics analyses to characterize its predicted structural and functional features. Gain- and loss-of-function experiments demonstrated that modulation of TLR2 expression significantly altered the transcription of HF growth- and development-associated genes, including BCL2, CCND1, CTNNB1, FGF2, and TGFβ. Functional assays, including CCK-8 proliferation analysis, EdU incorporation, and immunostaining for proliferating cell nuclear antigen (PCNA), consistently showed that TLR2 overexpression markedly enhanced DPC proliferation, whereas TLR2 knockdown exerted a pronounced inhibitory effect. These results provide mechanistic insight into the role of TLR2 in regulating DPC proliferation and offer a theoretical basis for further investigations into its contribution to hair follicle biology.
{"title":"The role of the TLR2 gene in regulating proliferation of rabbit dermal papilla cells","authors":"Yu Zhou , Bohao Zhao , Shaoning Sun , Xiaoman Han , Yongqi Yu , Jinbao Li , Yang Chen , Xinsheng Wu","doi":"10.1016/j.bbrc.2026.153323","DOIUrl":"10.1016/j.bbrc.2026.153323","url":null,"abstract":"<div><div>Hair follicle (HF) morphogenesis, growth, and regeneration are fundamentally governed by reciprocal interactions between the epidermal and dermal compartments of the skin, with dermal papilla cells (DPCs) serving as a central regulatory element in this process. Here, the functional role of Toll-like receptor 2 (TLR2) in the control of DPC proliferation was investigated. The coding sequence (CDS) of the rabbit <em>TLR2</em> gene was successfully cloned and subjected to preliminary bioinformatics analyses to characterize its predicted structural and functional features. Gain- and loss-of-function experiments demonstrated that modulation of <em>TLR2</em> expression significantly altered the transcription of HF growth- and development-associated genes, including <em>BCL2</em>, <em>CCND1</em>, <em>CTNNB1</em>, <em>FGF2</em>, and <em>TGFβ</em>. Functional assays, including CCK-8 proliferation analysis, EdU incorporation, and immunostaining for proliferating cell nuclear antigen (PCNA), consistently showed that <em>TLR2</em> overexpression markedly enhanced DPC proliferation, whereas <em>TLR2</em> knockdown exerted a pronounced inhibitory effect. These results provide mechanistic insight into the role of TLR2 in regulating DPC proliferation and offer a theoretical basis for further investigations into its contribution to hair follicle biology.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"803 ","pages":"Article 153323"},"PeriodicalIF":2.2,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146049045","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 : 2026-01-21DOI: 10.1016/j.bbrc.2026.153341
Chong Guo , Kaiqiong Liao , Kai Xu , Jiongfeng Zhang , Guanglong Chen , Xiaohui Luo , Jun Yang , Zhengzai Dai , Xiao-Bin Lv , Feifei Zhang , Zhiping Zhang
Background
This research investigates the function of dihydrolipoic acid succinyltransferase (DLST) in the initiation and progression of osteosarcoma.
Methods
Cellular functions were assessed using CCK-8, colony formation, scratch assays, transwell assays, and flow cytometry. The expression of relevant genes at both mRNA and protein levels was detected using quantitative real-time PCR (qRT-PCR) and Western blotting techniques. The regulatory mechanism of DLST was analyzed through RNA-sequencing. Finally, tumor growth in vivo was evaluated using established animal models.
Results
DLST was highly expressed in osteosarcoma. Knockdown of DLST limited the proliferative, migratory, invasive, and anti-apoptotic abilities of osteosarcoma cells. RNA-seq was employed to analyze its mechanism, which showed that DLST can influence the p38 MAPK signaling pathway. Functional validation further showed that the p38 MAPK signaling pathway inhibitor was able to reverse the malignant functional changes in osteosarcoma cells that had been caused by DLST knockdown. Finally, in in vivo experiments, knocking down the DLST gene in the osteosarcoma animal model slowed down tumor growth.
Conclusion
In this study, we found that DLST promotes the proliferation, migration, invasion, anti-apoptosis of osteosarcoma cells, as well as tumor growth, regulated through the p38 MAPK signaling pathway. These results could offer novel and valuable perspectives for the clinical management of osteosarcoma.
{"title":"DLST mediates the malignant progression of osteosarcoma cells by regulating the p38 MAPK signaling pathway","authors":"Chong Guo , Kaiqiong Liao , Kai Xu , Jiongfeng Zhang , Guanglong Chen , Xiaohui Luo , Jun Yang , Zhengzai Dai , Xiao-Bin Lv , Feifei Zhang , Zhiping Zhang","doi":"10.1016/j.bbrc.2026.153341","DOIUrl":"10.1016/j.bbrc.2026.153341","url":null,"abstract":"<div><h3>Background</h3><div>This research investigates the function of dihydrolipoic acid succinyltransferase (DLST) in the initiation and progression of osteosarcoma.</div></div><div><h3>Methods</h3><div>Cellular functions were assessed using CCK-8, colony formation, scratch assays, transwell assays, and flow cytometry. The expression of relevant genes at both mRNA and protein levels was detected using quantitative real-time PCR (qRT-PCR) and Western blotting techniques. The regulatory mechanism of DLST was analyzed through RNA-sequencing. Finally, tumor growth in vivo was evaluated using established animal models.</div></div><div><h3>Results</h3><div>DLST was highly expressed in osteosarcoma. Knockdown of DLST limited the proliferative, migratory, invasive, and anti-apoptotic abilities of osteosarcoma cells. RNA-seq was employed to analyze its mechanism, which showed that DLST can influence the p38 MAPK signaling pathway. Functional validation further showed that the p38 MAPK signaling pathway inhibitor was able to reverse the malignant functional changes in osteosarcoma cells that had been caused by DLST knockdown. Finally, in in vivo experiments, knocking down the DLST gene in the osteosarcoma animal model slowed down tumor growth.</div></div><div><h3>Conclusion</h3><div>In this study, we found that DLST promotes the proliferation, migration, invasion, anti-apoptosis of osteosarcoma cells, as well as tumor growth, regulated through the p38 MAPK signaling pathway. These results could offer novel and valuable perspectives for the clinical management of osteosarcoma.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"803 ","pages":"Article 153341"},"PeriodicalIF":2.2,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146076709","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 : 2026-01-21DOI: 10.1016/j.bbrc.2026.153337
Yunmin Xie , Lu Chen , Fuqiao Liu, Qian Zheng, Lei Yuan, Hui Xiao, Hui Wang
Apoptosis, a principal form of programmed cell death, is integral to animal development. Neuropeptides, which are crucial signaling molecules in the nervous system, play roles in various physiological and behavioral processes. Until now, there has been no evidence of neuropeptides being involved in the clearance of apoptotic cells. Consequently, utilizing Caenorhabditis elegans—an exemplary model organism for investigating apoptosis and its regulatory mechanisms—we performed a comprehensive functional screening of neuropeptide genes via RNA interference (RNAi) technology to identify pivotal neuropeptide genes involved in apoptosis and apoptotic cell clearance. C. elegans possesses 113 neuropeptide genes. Our screening identified 9 neuropeptide genes as preliminary regulators of apoptosis, with 2 neuropeptide genes specifically involved in apoptotic cell clearance. Among these, the neuropeptide gene ins-14 exhibited the most significant regulatory phenotype. Further mechanistic investigations revealed that, during the late stage of apoptotic cell clearance, disruptions in ins-14 function markedly affect the recruitment efficiency of the key protein LAAT-1 to phagosomes and disrupt the normal acidification process within phagosomes. Moreover, we found that ins-14 modulated laat-1 expression at the transcriptional level. This study is the first to elucidate the regulatory role of neuropeptides in apoptotic cell clearance in C. elegans, offering novel experimental evidence for a more profound understanding of neuropeptide-mediated apoptotic regulatory networks.
{"title":"Neuropeptide INS-14 modulates apoptotic cell clearance in Caenorhabditis elegans","authors":"Yunmin Xie , Lu Chen , Fuqiao Liu, Qian Zheng, Lei Yuan, Hui Xiao, Hui Wang","doi":"10.1016/j.bbrc.2026.153337","DOIUrl":"10.1016/j.bbrc.2026.153337","url":null,"abstract":"<div><div>Apoptosis, a principal form of programmed cell death, is integral to animal development. Neuropeptides, which are crucial signaling molecules in the nervous system, play roles in various physiological and behavioral processes. Until now, there has been no evidence of neuropeptides being involved in the clearance of apoptotic cells. Consequently, utilizing <em>Caenorhabditis elegans</em>—an exemplary model organism for investigating apoptosis and its regulatory mechanisms—we performed a comprehensive functional screening of neuropeptide genes via RNA interference (RNAi) technology to identify pivotal neuropeptide genes involved in apoptosis and apoptotic cell clearance. <em>C. elegans</em> possesses 113 neuropeptide genes. Our screening identified 9 neuropeptide genes as preliminary regulators of apoptosis, with 2 neuropeptide genes specifically involved in apoptotic cell clearance. Among these, the neuropeptide gene <em>ins-14</em> exhibited the most significant regulatory phenotype. Further mechanistic investigations revealed that, during the late stage of apoptotic cell clearance, disruptions in <em>ins-14</em> function markedly affect the recruitment efficiency of the key protein LAAT-1 to phagosomes and disrupt the normal acidification process within phagosomes. Moreover, we found that <em>ins-14</em> modulated <em>laat-1</em> expression at the transcriptional level. This study is the first to elucidate the regulatory role of neuropeptides in apoptotic cell clearance in <em>C. elegans</em>, offering novel experimental evidence for a more profound understanding of neuropeptide-mediated apoptotic regulatory networks.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"803 ","pages":"Article 153337"},"PeriodicalIF":2.2,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146049046","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}
Nonsteroidal mineralocorticoid receptor antagonists (MRAs) have emerged as promising therapies for cardiovascular disease. Finerenone, a highly selective nonsteroidal MRA, has shown efficacy in slowing the progression of heart failure with mildly reduced or preserved ejection fraction, as demonstrated in the FINEARTS-HF trial. However, its mechanisms of action, particularly in heart failure with preserved ejection fraction (HFpEF), remain poorly understood.
Methods
We established a murine model of HFpEF characterized by obesity, metabolic dysfunction-associated fatty liver disease, type 2 diabetes, and hypertension-induced cardiac hypertrophy. This was induced through long-term administration of a high-fat, high-fructose diet combined with NG-nitro-l-arginine methyl ester (l-NAME). Finerenone was administered during the early stage of myocardial remodeling, coinciding with the first histological evidence of cardiac hypertrophy. Cardiac function and structure were evaluated using transthoracic echocardiography, 24-h ambulatory blood pressure monitoring, and histological analysis. To investigate cardiomyocyte-specific transcriptional changes, we performed RNA sequencing on isolated cardiomyocyte nuclei.
Results
Fifteen weeks of combined metabolic and hypertensive stress resulted in obesity, glucose intolerance, hypertension, reduced exercise capacity, and myocardial hypertrophy. Finerenone, administered during the final two weeks, significantly attenuated myocardial hypertrophy without affecting systemic blood pressure. Cardiomyocyte-specific transcriptomic analysis revealed downregulation of hypertrophic gene expression and upregulation of glucocorticoid receptor (GR)-responsive genes.
Conclusions
Finerenone alleviates early-stage cardiac hypertrophy in a murine HFpEF model driven by metabolic and hemodynamic stress. Its cardioprotective effects appear to be independent of systemic blood pressure reduction and may involve modulation of GR signaling pathways in cardiomyocytes.
{"title":"Nonsteroidal mineralocorticoid receptor antagonist finerenone ameliorates cardiac hypertrophy with increasing glucocorticoid signaling sensitivity","authors":"Kei Morikawa , Yuichiro Arima , Takumi Nagakura , Yuqing Xu , Akira Fujiyama , Miho Kataoka , Shinsuke Hanatani , Yasushi Matsuzawa , Yasuhiro Izumiya , Eiichiro Yamamoto , Kenichi Tsujita","doi":"10.1016/j.bbrc.2026.153332","DOIUrl":"10.1016/j.bbrc.2026.153332","url":null,"abstract":"<div><h3>Background</h3><div>Nonsteroidal mineralocorticoid receptor antagonists (MRAs) have emerged as promising therapies for cardiovascular disease. Finerenone, a highly selective nonsteroidal MRA, has shown efficacy in slowing the progression of heart failure with mildly reduced or preserved ejection fraction, as demonstrated in the FINEARTS-HF trial. However, its mechanisms of action, particularly in heart failure with preserved ejection fraction (HFpEF), remain poorly understood.</div></div><div><h3>Methods</h3><div>We established a murine model of HFpEF characterized by obesity, metabolic dysfunction-associated fatty liver disease, type 2 diabetes, and hypertension-induced cardiac hypertrophy. This was induced through long-term administration of a high-fat, high-fructose diet combined with NG-nitro-<span>l</span>-arginine methyl ester (<span>l</span>-NAME). Finerenone was administered during the early stage of myocardial remodeling, coinciding with the first histological evidence of cardiac hypertrophy. Cardiac function and structure were evaluated using transthoracic echocardiography, 24-h ambulatory blood pressure monitoring, and histological analysis. To investigate cardiomyocyte-specific transcriptional changes, we performed RNA sequencing on isolated cardiomyocyte nuclei.</div></div><div><h3>Results</h3><div>Fifteen weeks of combined metabolic and hypertensive stress resulted in obesity, glucose intolerance, hypertension, reduced exercise capacity, and myocardial hypertrophy. Finerenone, administered during the final two weeks, significantly attenuated myocardial hypertrophy without affecting systemic blood pressure. Cardiomyocyte-specific transcriptomic analysis revealed downregulation of hypertrophic gene expression and upregulation of glucocorticoid receptor (GR)-responsive genes.</div></div><div><h3>Conclusions</h3><div>Finerenone alleviates early-stage cardiac hypertrophy in a murine HFpEF model driven by metabolic and hemodynamic stress. Its cardioprotective effects appear to be independent of systemic blood pressure reduction and may involve modulation of GR signaling pathways in cardiomyocytes.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"802 ","pages":"Article 153332"},"PeriodicalIF":2.2,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146025590","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 : 2026-01-20DOI: 10.1016/j.bbrc.2026.153301
Kishore Babu Naripogu , Yee Han Tee , Yosuke Senju , Alexander Bershadsky , Robert C. Robinson
The emergence of internal membrane systems was a defining step in eukaryogenesis, but how pre-eukaryotic proteins were adapted to these novel compartments and structures remains unclear. Asgard archaea, the closest known prokaryotic relatives of eukaryotes, encode homologs of ESCRT (Endosomal Sorting Complex Required for Transport) proteins, which mediate membrane remodeling in eukaryotic cells, processes ranging from endosomal sorting to cytokinetic abscission. Here, we show that ESCRT-II and ESCRT-III homologs, VSP4 and ubiquitin from the Asgard achaeon Promethearchaeum syntrophicum (MK-D1) are recruited to discrete structures when expressed in human cells. These archaeal proteins localize to canonical eukaryotic ESCRT recruitment sites, midbodies and centrosomes, structures which are absent from MK-D1. This localization reflects conserved molecular interactions that predate the emergence of eukaryotic internal membranes and other eukaryotic cellular structures. These findings support a model in which protein machines were repurposed to support cellular complexity during eukaryogenesis, allowing the integration of ancestral ESCRT molecular functions and networks in to novel cellular architectures.
{"title":"Localization of Asgard archaeal ESCRT proteins to eukaryotic cellular structures","authors":"Kishore Babu Naripogu , Yee Han Tee , Yosuke Senju , Alexander Bershadsky , Robert C. Robinson","doi":"10.1016/j.bbrc.2026.153301","DOIUrl":"10.1016/j.bbrc.2026.153301","url":null,"abstract":"<div><div>The emergence of internal membrane systems was a defining step in eukaryogenesis, but how pre-eukaryotic proteins were adapted to these novel compartments and structures remains unclear. Asgard archaea, the closest known prokaryotic relatives of eukaryotes, encode homologs of ESCRT (Endosomal Sorting Complex Required for Transport) proteins, which mediate membrane remodeling in eukaryotic cells, processes ranging from endosomal sorting to cytokinetic abscission. Here, we show that ESCRT-II and ESCRT-III homologs, VSP4 and ubiquitin from the Asgard achaeon <em>Promethearchaeum syntrophicum</em> (MK-D1) are recruited to discrete structures when expressed in human cells. These archaeal proteins localize to canonical eukaryotic ESCRT recruitment sites, midbodies and centrosomes, structures which are absent from MK-D1. This localization reflects conserved molecular interactions that predate the emergence of eukaryotic internal membranes and other eukaryotic cellular structures. These findings support a model in which protein machines were repurposed to support cellular complexity during eukaryogenesis, allowing the integration of ancestral ESCRT molecular functions and networks in to novel cellular architectures.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"802 ","pages":"Article 153301"},"PeriodicalIF":2.2,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146025591","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 : 2026-01-20DOI: 10.1016/j.bbrc.2026.153310
Qing Zhu , Mao Zhao , Weinan Guo , Huina Wang
Melanoma represents the most aggressive and lethal form of skin cancer with high metastatic potential and elucidating the mechanisms underlying its progression is essential for developing effective therapies. The mitochondrial pyruvate carrier 1 (MPC1) is critical in linking glycolysis and oxidative phosphorylation, which has also been implicated in the pathogenesis of various cancers, yet its role in melanoma progression remains poorly understood. In this study, we found that MPC1 was markedly downregulated in both melanoma cell lines and tissues compared to control, and the alteration was more prominent in metastatic stage. Functional studies revealed that MPC1 deficiency enhanced melanoma cell proliferation, migration, and invasion in vitro and augmented melanoma metastasis in vivo. Mechanistically, RNA sequencing and subsequent functional study have demonstrated that MPC1 suppressed the activation of Wnt/β-catenin pathway by regulating DKK3, a key Wnt antagonist. Furthermore, pharmacologic inhibition of Wnt/β-catenin abrogated the pro-tumorigenic effects of MPC1 knockdown both in vitro and in vivo. Collectively, these data demonstrated that MPC1 deficiency promotes melanoma progression via Wnt/β-catenin signaling that is associated with DKK3 regulation. Targeting MPC1-Wnt/β-catenin axis may represent a novel therapeutic strategy for advanced melanoma treatment.
{"title":"MPC1 deficiency promotes melanoma progression via Wnt/β-catenin signaling","authors":"Qing Zhu , Mao Zhao , Weinan Guo , Huina Wang","doi":"10.1016/j.bbrc.2026.153310","DOIUrl":"10.1016/j.bbrc.2026.153310","url":null,"abstract":"<div><div>Melanoma represents the most aggressive and lethal form of skin cancer with high metastatic potential and elucidating the mechanisms underlying its progression is essential for developing effective therapies. The mitochondrial pyruvate carrier 1 (MPC1) is critical in linking glycolysis and oxidative phosphorylation, which has also been implicated in the pathogenesis of various cancers, yet its role in melanoma progression remains poorly understood. In this study, we found that MPC1 was markedly downregulated in both melanoma cell lines and tissues compared to control, and the alteration was more prominent in metastatic stage. Functional studies revealed that MPC1 deficiency enhanced melanoma cell proliferation, migration, and invasion <em>in vitro</em> and augmented melanoma metastasis <em>in vivo</em>. Mechanistically, RNA sequencing and subsequent functional study have demonstrated that MPC1 suppressed the activation of Wnt/β-catenin pathway by regulating DKK3, a key Wnt antagonist. Furthermore, pharmacologic inhibition of Wnt/β-catenin abrogated the pro-tumorigenic effects of MPC1 knockdown both <em>in vitro</em> and <em>in vivo</em>. Collectively, these data demonstrated that MPC1 deficiency promotes melanoma progression via Wnt/β-catenin signaling that is associated with DKK3 regulation. Targeting MPC1-Wnt/β-catenin axis may represent a novel therapeutic strategy for advanced melanoma treatment.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"801 ","pages":"Article 153310"},"PeriodicalIF":2.2,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146036749","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 : 2026-01-20DOI: 10.1016/j.bbrc.2026.153298
Jianing Zhang , Xiaodong Zhao , Huilian Xu , Xiaoyong Liu , Yan He , Xiaojun Tan , Jinsong Gu
{"title":"Corrigendum to “NMN synbiotics intervention modulates gut microbiota and metabolism in APP/PS1 Alzheimer's disease mouse models” [Biochem. Biophys. Res. Commun. 726 (2024) 150–274]","authors":"Jianing Zhang , Xiaodong Zhao , Huilian Xu , Xiaoyong Liu , Yan He , Xiaojun Tan , Jinsong Gu","doi":"10.1016/j.bbrc.2026.153298","DOIUrl":"10.1016/j.bbrc.2026.153298","url":null,"abstract":"","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"801 ","pages":"Article 153298"},"PeriodicalIF":2.2,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146016950","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 : 2026-01-20DOI: 10.1016/j.bbrc.2026.153322
Jian Cheng , Mingming Liu , Qianyu Li , Lu Zhao , Qi Zhang
Macrophage polarization plays a pivotal role in maintaining bone homeostasis and serves as a crucial mechanistic bridge in the comorbidity of osteoarthritis (OA) and osteoporosis (OP). Macrophages exhibit functional plasticity, polarizing into pro-inflammatory M1 and anti-inflammatory M2 phenotypes in response to various environmental cues. Recent advances in macrophage biology have highlighted the significant heterogeneity of macrophages, which display a spectrum of phenotypic states beyond the classical M1/M2 dichotomy. Dysregulated macrophage polarization, particularly an excess of M1 macrophages, is central to the pathophysiological mechanisms underlying OA and OP. This review systematically explores how altered macrophage polarization influences OA and OP pathogenesis, emphasizing its role in inflammatory responses, metabolic syndrome, and the mechanical microenvironment. In particular, macrophage polarization within the subchondral bone-cartilage interface has emerged as a key factor in exacerbating joint and bone degeneration. Imbalances in macrophage polarization are shown to contribute to cartilage degradation, bone loss, and disrupted bone remodeling processes in these diseases. Additionally, exosomal non-coding RNAs (Exos-ncRNAs) have been identified as important modulators of macrophage polarization, offering potential therapeutic targets for restoring M2-mediated repair functions and reducing M1-driven inflammation. Targeting specific macrophage polarization pathways holds promise for developing integrated therapeutic strategies to address both OA and OP by restoring immune-metabolic homeostasis, enhancing tissue repair, and promoting bone regeneration.
{"title":"Macrophage polarization: A bridge connecting osteoarthritis and osteoporosis","authors":"Jian Cheng , Mingming Liu , Qianyu Li , Lu Zhao , Qi Zhang","doi":"10.1016/j.bbrc.2026.153322","DOIUrl":"10.1016/j.bbrc.2026.153322","url":null,"abstract":"<div><div>Macrophage polarization plays a pivotal role in maintaining bone homeostasis and serves as a crucial mechanistic bridge in the comorbidity of osteoarthritis (OA) and osteoporosis (OP). Macrophages exhibit functional plasticity, polarizing into pro-inflammatory M1 and anti-inflammatory M2 phenotypes in response to various environmental cues. Recent advances in macrophage biology have highlighted the significant heterogeneity of macrophages, which display a spectrum of phenotypic states beyond the classical M1/M2 dichotomy. Dysregulated macrophage polarization, particularly an excess of M1 macrophages, is central to the pathophysiological mechanisms underlying OA and OP. This review systematically explores how altered macrophage polarization influences OA and OP pathogenesis, emphasizing its role in inflammatory responses, metabolic syndrome, and the mechanical microenvironment. In particular, macrophage polarization within the subchondral bone-cartilage interface has emerged as a key factor in exacerbating joint and bone degeneration. Imbalances in macrophage polarization are shown to contribute to cartilage degradation, bone loss, and disrupted bone remodeling processes in these diseases. Additionally, exosomal non-coding RNAs (Exos-ncRNAs) have been identified as important modulators of macrophage polarization, offering potential therapeutic targets for restoring M2-mediated repair functions and reducing M1-driven inflammation. Targeting specific macrophage polarization pathways holds promise for developing integrated therapeutic strategies to address both OA and OP by restoring immune-metabolic homeostasis, enhancing tissue repair, and promoting bone regeneration.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"801 ","pages":"Article 153322"},"PeriodicalIF":2.2,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146036720","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 : 2026-01-20DOI: 10.1016/j.bbrc.2026.153303
Changsheng Lin , Chunyan Liu , Xiao Zhang , Fang Zhou , Yuqin Ma , Ziqi Ye , Kaizong Huang , Anliang Chen , Kai Cheng , Xueping Li
Osteoarthritis (OA) is a progressive degenerative joint disease characterized by cartilage degradation, inflammation, and pain. High-intensity interval training (HIIT) has emerged as a promising non-pharmacological intervention that may improve joint function by promoting cartilage repair and attenuating inflammation. This study investigated the effects of HIIT on cartilage ferroptosis and the underlying molecular mechanisms, focusing on SIRT1 in a rat model of knee OA.
Sprague–Dawley rats were induced with OA via intra-articular monosodium iodoacetate (MIA) and then subjected to a 6-week HIIT program. Outcomes included gait analysis, mechanical and thermal pain thresholds, histological staining, and molecular assays. HIIT significantly improved gait parameters and pain thresholds, indicating functional recovery. Histology showed enhanced cartilage matrix integrity and repair. HIIT modulated ferroptosis-related markers, including GPX4 and ACSL4, and upregulated SIRT1 with activation of NRF2 signaling and improved iron metabolism within cartilage. Pharmacologic inhibition of SIRT1 (EX527) reversed these benefits, underscoring SIRT1's pivotal role in mediating HIIT's therapeutic effects. In vitro, IL-1β-stimulated primary chondrocytes exhibited reduced SIRT1/NRF2/GPX4 and increased TFRC/ACSL4, whereas lentiviral SIRT1 overexpression restored NRF2-GPX4 signaling and decreased TFRC/ACSL4, supporting a chondrocyte-intrinsic SIRT1-NRF2-GPX4 axis in regulating ferroptosis-associated responses.
In conclusion, while direct evidence of ferroptosis markers such as lipid peroxidation and mitochondrial changes is lacking, HIIT alleviates ferroptosis-associated cartilage damage and promotes cartilage repair in OA through SIRT1-dependent mechanisms. These findings support HIIT as a potential non-pharmacological strategy for OA management and provide a mechanistic basis for exercise-based interventions aimed at preserving joint function and reducing OA-related disability.
{"title":"High-intensity interval training promotes cartilage repair and ameliorates ferroptosis via SIRT1 in osteoarthritis","authors":"Changsheng Lin , Chunyan Liu , Xiao Zhang , Fang Zhou , Yuqin Ma , Ziqi Ye , Kaizong Huang , Anliang Chen , Kai Cheng , Xueping Li","doi":"10.1016/j.bbrc.2026.153303","DOIUrl":"10.1016/j.bbrc.2026.153303","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a progressive degenerative joint disease characterized by cartilage degradation, inflammation, and pain. High-intensity interval training (HIIT) has emerged as a promising non-pharmacological intervention that may improve joint function by promoting cartilage repair and attenuating inflammation. This study investigated the effects of HIIT on cartilage ferroptosis and the underlying molecular mechanisms, focusing on SIRT1 in a rat model of knee OA.</div><div>Sprague–Dawley rats were induced with OA via intra-articular monosodium iodoacetate (MIA) and then subjected to a 6-week HIIT program. Outcomes included gait analysis, mechanical and thermal pain thresholds, histological staining, and molecular assays. HIIT significantly improved gait parameters and pain thresholds, indicating functional recovery. Histology showed enhanced cartilage matrix integrity and repair. HIIT modulated ferroptosis-related markers, including GPX4 and ACSL4, and upregulated SIRT1 with activation of NRF2 signaling and improved iron metabolism within cartilage. Pharmacologic inhibition of SIRT1 (EX527) reversed these benefits, underscoring SIRT1's pivotal role in mediating HIIT's therapeutic effects. In vitro, IL-1β-stimulated primary chondrocytes exhibited reduced SIRT1/NRF2/GPX4 and increased TFRC/ACSL4, whereas lentiviral SIRT1 overexpression restored NRF2-GPX4 signaling and decreased TFRC/ACSL4, supporting a chondrocyte-intrinsic SIRT1-NRF2-GPX4 axis in regulating ferroptosis-associated responses.</div><div>In conclusion, while direct evidence of ferroptosis markers such as lipid peroxidation and mitochondrial changes is lacking, HIIT alleviates ferroptosis-associated cartilage damage and promotes cartilage repair in OA through SIRT1-dependent mechanisms. These findings support HIIT as a potential non-pharmacological strategy for OA management and provide a mechanistic basis for exercise-based interventions aimed at preserving joint function and reducing OA-related disability.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"804 ","pages":"Article 153303"},"PeriodicalIF":2.2,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146071120","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 : 2026-01-20DOI: 10.1016/j.bbrc.2026.153327
Yuqi Shen , Chunyang Liu , Zewei Wang , Hongxu Jin , Ying Liu
The Krüppel-like Factor 2 (KLF2) -Thrombomodulin (TM) axis is crucial for maintaining vascular homeostasis and coagulation balance. This study investigated its dynamic role and temporal characteristics in the development of coagulopathy following exertional heat stroke (EHS). Using a well-established rat model of EHS induced by strenuous exercise under high-temperature and high-humidity conditions, we conducted a detailed time-course analysis. Our findings revealed that plasma levels of KLF2 and TM underwent significant dynamic fluctuations following EHS induction. These alterations showed a clear correlation with progressive prolongations in standard coagulation parameters, specifically activated partial thromboplastin time (APTT) and prothrombin time (PT). The most profound disturbances in both the KLF2-TM axis and coagulation function were consistently observed at 4 h post-EHS. Notably, this critical time point was also associated with the peak severity of hepatic injury, as comprehensively assessed through histopathological examination and confirmatory liver function tests. Further analysis demonstrated that the aberrant expression of the KLF2-TM pathway within the liver tissue exhibited a distinct temporal consistency with the observed progression of hepatic pathological damage. Collectively, these results indicated that the KLF2-TM axis was actively involved in the pathogenic mechanisms underlying EHS-associated coagulopathy. Monitoring the dynamic changes of this axis may provide valuable predictive insights into the dysregulation of coagulation during EHS, suggesting its potential as a biomarker for disease severity.
{"title":"Temporal changes in Krüppel-like factor 2 and thrombomodulin correlate with coagulation, endothelial, and liver damage in exertional heat stroke rats","authors":"Yuqi Shen , Chunyang Liu , Zewei Wang , Hongxu Jin , Ying Liu","doi":"10.1016/j.bbrc.2026.153327","DOIUrl":"10.1016/j.bbrc.2026.153327","url":null,"abstract":"<div><div>The Krüppel-like Factor 2 (KLF2) -Thrombomodulin (TM) axis is crucial for maintaining vascular homeostasis and coagulation balance. This study investigated its dynamic role and temporal characteristics in the development of coagulopathy following exertional heat stroke (EHS). Using a well-established rat model of EHS induced by strenuous exercise under high-temperature and high-humidity conditions, we conducted a detailed time-course analysis. Our findings revealed that plasma levels of KLF2 and TM underwent significant dynamic fluctuations following EHS induction. These alterations showed a clear correlation with progressive prolongations in standard coagulation parameters, specifically activated partial thromboplastin time (APTT) and prothrombin time (PT). The most profound disturbances in both the KLF2-TM axis and coagulation function were consistently observed at 4 h post-EHS. Notably, this critical time point was also associated with the peak severity of hepatic injury, as comprehensively assessed through histopathological examination and confirmatory liver function tests. Further analysis demonstrated that the aberrant expression of the KLF2-TM pathway within the liver tissue exhibited a distinct temporal consistency with the observed progression of hepatic pathological damage. Collectively, these results indicated that the KLF2-TM axis was actively involved in the pathogenic mechanisms underlying EHS-associated coagulopathy. Monitoring the dynamic changes of this axis may provide valuable predictive insights into the dysregulation of coagulation during EHS, suggesting its potential as a biomarker for disease severity.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"802 ","pages":"Article 153327"},"PeriodicalIF":2.2,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146025593","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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