Biochemical and biophysical research communications最新文献_第9页

BDH1 reduces apoptosis and alleviates mitochondrial damage of cardiomyocytes under high glucose condition as a downstream target of miR-125b

IF 2.5 3区生物学

Biochemical and biophysical research communications Pub Date : 2025-03-13 DOI: 10.1016/j.bbrc.2025.151561

Bincheng Ren , Zhiyi Fang , Yimin Zhang , Huan Yang , Lingjuan Gou , Miao Yuan , Yu Wang , Dengfeng Gao

{"title":"BDH1 reduces apoptosis and alleviates mitochondrial damage of cardiomyocytes under high glucose condition as a downstream target of miR-125b","authors":"Bincheng Ren , Zhiyi Fang , Yimin Zhang , Huan Yang , Lingjuan Gou , Miao Yuan , Yu Wang , Dengfeng Gao","doi":"10.1016/j.bbrc.2025.151561","DOIUrl":"10.1016/j.bbrc.2025.151561","url":null,"abstract":"<div><div>Diabetes is a chronic metabolic disease, characterized prominently by a persistent elevation of blood glucose level beyond the normal range. Prolonged hyperglycemia exerts deleterious effects on systems and organs of the body, leading to complications like diabetic cardiomyopathy (DCM). Our study commenced by screening the gene 3-hydroxybutyrate dehydrogenase 1 (BDH1) with low expression in DCM via Gene Expression Omnibus (GEO) analysis (GSE123975). Subsequently, we cultivated AC16 human cardiomyocytes in high glucose (HG) conditions and observed a reduction in BDH1 expression. To further investigate, we constructed plasmids for BDH1 knockdown (sh-BDH1) and overexpression (OE-BDH1). When BDH1 was overexpressed in HG-treated AC16 cells, apoptosis decreased, with reduced Bax/Bcl2 and Cleaved Caspase3/Caspase3 ratios. Additionally, mitochondrial ROS decreased, while expression of mitochondrial fusion protein mitofusin 2 (MFN2) and mitochondrial repair protein folliculin interacting protein 1 (FNIP1) increased. Notably, microRNA-125 b was upregulated in AC16 cells with hyperglycemia, and dual-luciferase reporter assays confirmed its targeting and inhibition of BDH1 mRNA. Inhibition of miR-125 b in HG-treated AC16 cells reversed apoptosis and mitochondrial ROS increase, yet simultaneous inhibition of both miR-125 b and BDH1 abolished this effect. In addition, we overexpressed BDH1 in diabetic mice by tail vein injection, and proved that overexpression of BDH1 could reduce cardiomyocyte apoptosis <em>in vivo</em>. In conclusion, our findings suggested that the miR-125-BDH1 axis could inhibit the production of mitochondrial ROS, promote mitochondrial fusion and repair, and reduce the apoptosis and mitochondrial damage of cardiomyocytes in HG condition.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"757 ","pages":"Article 151561"},"PeriodicalIF":2.5,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143627910","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}

引用次数: 0

The experimental study of the effect of fluid shear force on the migration rate of human umbilical vein endothelial cells

IF 2.5 3区生物学

Biochemical and biophysical research communications Pub Date : 2025-03-13 DOI: 10.1016/j.bbrc.2025.151619

Dong Chen , Xianwei Wang , Sen Zhang , Jiaming Huang , Mei Li , Liding Wang , Tao Jiang

{"title":"The experimental study of the effect of fluid shear force on the migration rate of human umbilical vein endothelial cells","authors":"Dong Chen , Xianwei Wang , Sen Zhang , Jiaming Huang , Mei Li , Liding Wang , Tao Jiang","doi":"10.1016/j.bbrc.2025.151619","DOIUrl":"10.1016/j.bbrc.2025.151619","url":null,"abstract":"<div><h3>Background</h3><div>The vascular endothelium is a continuous monolayer of flattened cells that cover the surface of the lumen of blood vessels. Endothelial cell damage can readily result in thrombus formation and thickening of the intima. Accelerating the migration and repair of peripheral endothelial cells is essential. Shear force is an important hydrodynamic factor affecting endothelial cell function. We aimed to investigate the effect of different shear forces on the migration rate of endothelial cells.</div></div><div><h3>Methods</h3><div>Human umbilical vein endothelial cells (HUVECs) were used instead of endothelial cells to establish a cell scratch model. Plate flow chambers were then used to intervene in HUVECs growth with different shear force magnitudes (4 dyn/cm<sup>2</sup>, 8 dyn/cm<sup>2</sup>, and 12 dyn/cm<sup>2</sup>). The healing rate of the scratches was observed under light microscopy, and finally the expression of RhoA and CDC42 was detected by molecular experiments. The expression of CDC42 factor was inhibited by siRNA interference, and the wound healing ability of HUVECs in the control group and the CDC42 inhibition group under different fluid shear forces was observed under light microscopy.</div></div><div><h3>Results</h3><div>High shear forces promote the healing of scratches. In addition, relatively strong shear forces promoted the expression of cytokines RhoA and CDC42. Compared with untransfected HUVECs, HUVECs with inhibition of CDC42 expression by siRNA interference showed weak migration ability in different fluid shear groups.</div></div><div><h3>Conclusion</h3><div>Increasing fluid shear force in a range (4–12 dyn/cm<sup>2</sup>) contributes to endothelial cell migration. Inhibition of CDC42 expression weakened the migration ability of HUVECs under different fluid shear forces.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"758 ","pages":"Article 151619"},"PeriodicalIF":2.5,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673531","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}

引用次数: 0

High-throughput screening unveils AMG 837 and RORγt 13 as the potent Brucella inhibitor by targeting BacA

IF 2.5 3区生物学

Biochemical and biophysical research communications Pub Date : 2025-03-12 DOI: 10.1016/j.bbrc.2025.151624

Kai-Xuan Guo , Hong-Xia Hu , Jian-Dong Zhang , Feng-Dong Zhu , Chao-Yue Guo , Guo-Hua Cai , Huan-Chun Chen , Zheng-Fei Liu

{"title":"High-throughput screening unveils AMG 837 and RORγt 13 as the potent Brucella inhibitor by targeting BacA","authors":"Kai-Xuan Guo , Hong-Xia Hu , Jian-Dong Zhang , Feng-Dong Zhu , Chao-Yue Guo , Guo-Hua Cai , Huan-Chun Chen , Zheng-Fei Liu","doi":"10.1016/j.bbrc.2025.151624","DOIUrl":"10.1016/j.bbrc.2025.151624","url":null,"abstract":"<div><div>Brucellosis poses a major threat to the global animal husbandry, yet effective prevention and control measures remain elusive. Through High-Throughput Screening techniques, two potential anti-<em>Brucella</em> compounds are identified from a library comprising FDA-approved and known biological activity in this study. We unveil AMG 837 calcium hydrate and RORγt inverse antigen 13 can strongly bind with BacA, which mutants lacking BacA greatly reduce the survival rate of <em>Brucella</em> in macrophages. AMG 837 calcium hydrate and RORγt inverse antigen 13 as the potent inhibitor of <em>Brucella</em> both <em>in vitro</em> and in cells, which can effectively eliminate bacteria that infect into cells at a concentration of only 16 μg/mL. These results indicate the promising potential of AMG 837 calcium hydrate and RORγt inverse antigen 13 as the repurposed therapeutic agent for brucellosis. Additionally, they provide valuable insights into the antibacterial mechanisms underlying effectiveness.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"757 ","pages":"Article 151624"},"PeriodicalIF":2.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143627909","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}

引用次数: 0

OsMADS22 interacts with OsMADS50 to regulate floral transition in rice

IF 2.5 3区生物学

Biochemical and biophysical research communications Pub Date : 2025-03-11 DOI: 10.1016/j.bbrc.2025.151607

Dongyang Wang , Yi Chai , Suhui Chen

{"title":"OsMADS22 interacts with OsMADS50 to regulate floral transition in rice","authors":"Dongyang Wang , Yi Chai , Suhui Chen","doi":"10.1016/j.bbrc.2025.151607","DOIUrl":"10.1016/j.bbrc.2025.151607","url":null,"abstract":"<div><div>Appropriate flowering time is critical for reproductive transition and is closely related to crop yield. In Arabidopsis, SVP, MADS-box containing proteins, interact with FLC to form a repressor complex to repress the expression level of <em>SOC1</em> and <em>FT</em> to control flowering time. <em>OsMADS22</em>, one of three SVP-clade MADS-box genes, has been shown that functions as a negative regulator on floral transition in rice. However, the molecular mechanism of <em>OsMADS22</em> in flowering time and genetic interaction between SVP and SOC1 homologs was unknown. In this study, we found that OsMADS22 could form homodimers and interact with OsMADS50, a putative rice ortholog of SOC1, to antagonistically regulate key flowering-related genes, including <em>OsMADS14</em>, <em>RFT1</em>, <em>Ehd1</em>, <em>Hd3a</em>, and <em>OsMADS1</em>. Notably, elevated expression levels of <em>OsMADS22</em> were detected in <em>osmads50</em> mutants, whereas the transcript abundance of <em>OsMADS50</em> remained unchanged under <em>OsMADS22-</em>overexpressing line compared with wild-type controls, suggesting that <em>OsMADS50</em> is not genetically epistatic to <em>OsMADS22</em>, unlike their homologs in Arabidopsis. Moreover, we showed that the interaction between OsMADS22 and OsMADS50 is mainly dependent on their K-box domains. OsMADS50 localize to the nucleus while its Arabidopsis homolog SVP localized in cytosol. Notably, we newly revealed additional roles for <em>OsMADS50</em> in rice grain development. Taken together, our results elucidate the regulatory pathways of <em>OsMADS22</em> on flowering time and reveal species-specific functional divergence between SVP and SOC1 in Arabidopsis and their homologs in rice, providing new insights into flowering time regulation in rice.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"757 ","pages":"Article 151607"},"PeriodicalIF":2.5,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143619881","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}

引用次数: 0

Unspliced XBP1 enhences metabolic reprogramming in colorectal cancer cells by interfering with the mitochondrial localization of MGME1

IF 2.5 3区生物学

Biochemical and biophysical research communications Pub Date : 2025-03-11 DOI: 10.1016/j.bbrc.2025.151613

Jiandong Zhang , Suyang Zhang , Fei Yu , Yuting Wan , Mingyue Wu , Can Huang

{"title":"Unspliced XBP1 enhences metabolic reprogramming in colorectal cancer cells by interfering with the mitochondrial localization of MGME1","authors":"Jiandong Zhang , Suyang Zhang , Fei Yu , Yuting Wan , Mingyue Wu , Can Huang","doi":"10.1016/j.bbrc.2025.151613","DOIUrl":"10.1016/j.bbrc.2025.151613","url":null,"abstract":"<div><div>Tumor cells undergo metabolic reprogramming, which makes them tend to utilize anaerobic glycolysis rather than oxidation to rapidly produce energy and intermediate products required for proliferation. In this process, mitochondria inevitably undergo corresponding alterations; however, the specific alterations in mitochondria across different cancer types and the mechanisms governing these changes remain poorly understood. This study demonstrated that unspliced X-box binding protein 1 (XBP1-u) inhibits the translocation of mitochondrial genome maintenance exonuclease 1 (MGME1) into mitochondria by binding to the mitochondrial targeting sequence (MTS) of MGME1. This interaction results in the accumulation of mitochondrial 7sDNA, a reduction in mitochondrial DNA copy number, and a decrease in mitochondrial abundance. Consequently, this shift enhances the production of glycolysis and pentose phosphate pathway intermediates, thereby promoting the proliferation of colorectal cancer (CRC) cells. Our findings elucidated the critical mechanism by which XBP1-u enhances metabolic reprogramming by modulating mitochondrial biogenesis, and uncovered a novel role of MGME1 in the progression of CRC.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"757 ","pages":"Article 151613"},"PeriodicalIF":2.5,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143619882","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}

引用次数: 0

Gene expression and characterization of an antimicrobial peptide from Medicago sativa “Sazova” cultivar

IF 2.5 3区生物学

Biochemical and biophysical research communications Pub Date : 2025-03-11 DOI: 10.1016/j.bbrc.2025.151617

Büşra Albayrak Turgut, Serkan Örtücü, İsmail Bezirganoğlu

{"title":"Gene expression and characterization of an antimicrobial peptide from Medicago sativa “Sazova” cultivar","authors":"Büşra Albayrak Turgut, Serkan Örtücü, İsmail Bezirganoğlu","doi":"10.1016/j.bbrc.2025.151617","DOIUrl":"10.1016/j.bbrc.2025.151617","url":null,"abstract":"<div><div>In recent years, the discovery of new antimicrobial agents has become necessary because of the increase in antibiotic resistance, the development of herbicides and fungicides resistance. Among the antimicrobial agents, antimicrobial peptides (AMPs) stand out due to their stable structure. In this study, the aim was to identify a thermostable AMP from the seeds of <em>M. sativa</em> “Sazova” cultivar and to analyze gene expression during germination. Antimicrobial tests were performed for the seed peptides after heat treatment (85 °C for 10 min), revealing antimicrobial effects against <em>S. aureus</em>, <em>E. coli</em>, and <em>C. albicans</em>. Subsequently, the peptide band corresponding to the inhibition zone was identified as <em>M. sativa</em> Defensin 2.1 (MsDef2.1, MW: 5.2048 kDa). The gene expression analysis of MsDef2.1 in Sazova cultivar showed that the gene was expressed different plant organs, and the expression was decreased over time. As a result of the gene analysis of two cultivars (Sazova and LegenDairy) it was found that there are 5 base differences in the coding sequence and 3 amino acid differences between the sequences of MsDef2.1 isoforms from the LegenDairy and Sazova cultivars. The physiochemical properties, secondary, and tertiary structure of the Sazova Defensin 2.1 were predicted by using bioinformatic tools. Due to the amino acid substitutions in γ-core structures, the antimicrobial activity of the isoforms is expected to differ from each other. These findings demonstrated that the defensin MsDef2.1 can differ in <em>M. sativa</em> cultivars in respect of the gene and amino acid sequences and has a potential for future applications.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"757 ","pages":"Article 151617"},"PeriodicalIF":2.5,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143637530","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}

引用次数: 0

Enhanced sampling simulations to explore himalayan phytochemicals as potential phosphodiesterase-1 inhibitor for neurological disorders

IF 2.5 3区生物学

Biochemical and biophysical research communications Pub Date : 2025-03-11 DOI: 10.1016/j.bbrc.2025.151614

Bhanu Sharma , Rituraj Purohit

{"title":"Enhanced sampling simulations to explore himalayan phytochemicals as potential phosphodiesterase-1 inhibitor for neurological disorders","authors":"Bhanu Sharma , Rituraj Purohit","doi":"10.1016/j.bbrc.2025.151614","DOIUrl":"10.1016/j.bbrc.2025.151614","url":null,"abstract":"<div><div>The rising incidence of neurological and neuropsychiatric disorders underscores the urgent need for innovative and evidence based treatment strategies. Phosphodiesterase-1 (PDE1) is a dual-substrate (cAMP/cGMP) phosphodiesterase expressed in the central nervous system and peripheral areas, which modulates cyclic nucleotide signaling cascades. Inhibiting PDE1 enhances cAMP/cGMP levels, promoting neuronal plasticity and neuroprotection, making it a promising therapeutic strategy for neurological disorders. The pursuit of targeting this enzyme for treating neurological and neuropsychiatric disorders has faced obstacles due to the absence of potent, selective, and brain-penetrating inhibitors. This study aimed to identify potent PDE1 inhibitors by leveraging a diverse collection of bioactive molecules derived from Himalayan flora through computational screening methods. The four most promising hit molecules were chosen for further investigation and subjected to Molecular Dynamics (MD) simulations, binding free energy calculations, along with standard molecules. It was found that the hit molecules stigmast-7, corilagin and emblicanin-A had formed the most stable complexes, and also, the least binding free energy was observed for stigmast-7 among the hit molecules. Additionally, the pulling simulations indicated that stigmast-7 and corilagin were the most robust binders, and required the highest force to dissociate from the binding cavity completely. The umbrella sampling simulations also revealed the lowest binding free energy for corilagin and stigmast-7. The insights gained from this study provide a foundation for future research into PDE1-targeted therapies, highlighting the potential of Himalayan bioactive compounds in developing novel therapeutic interventions.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"758 ","pages":"Article 151614"},"PeriodicalIF":2.5,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143643983","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}

引用次数: 0

The engineered dimer of L-arabinonate dehydratase from Rhizobium leguminosarum bv. trifolii: The role of intersubunit interactions in IlvD/EDD family

IF 2.5 3区生物学

Biochemical and biophysical research communications Pub Date : 2025-03-11 DOI: 10.1016/j.bbrc.2025.151610

Yaxin Ren, Elias Vettenranta, Leena Penttinen, Janne Jänis, Juha Rouvinen, Nina Hakulinen

{"title":"The engineered dimer of L-arabinonate dehydratase from Rhizobium leguminosarum bv. trifolii: The role of intersubunit interactions in IlvD/EDD family","authors":"Yaxin Ren, Elias Vettenranta, Leena Penttinen, Janne Jänis, Juha Rouvinen, Nina Hakulinen","doi":"10.1016/j.bbrc.2025.151610","DOIUrl":"10.1016/j.bbrc.2025.151610","url":null,"abstract":"<div><div>Engineering of protein oligomeric state or quaternary structure is a promising approach to adjust proteins for utilization in different applications and research. This study provides a detailed investigation of oligomerization within IlvD/EDD superfamily. A large 255 kDa tetrameric protein of the IlvD/EDD superfamily, L-arabinonate dehydratase from <em>Rhizobium leguminosarum</em> bv<em>. trifolii</em>, was engineered to create a dimeric form containing the [2Fe–2S] catalytic center. Four variants, which contain mutations at two locations of the dimer-dimer interface, were produced. The mutants were analyzed using UV–vis and native mass spectrometry, while iron composition and enzymatic activity with five substrates were also investigated. The three variants with mutations closer to the catalytic center showed a color change with shifted maximum absorption at 455 nm and had reduced catalytic activity. One of the variants, D39K, located farther from the active center, maintained a similar color to the wild-type enzyme. The D39K had a mild decline in the catalytic activity, and it existed in dimeric form. The three-dimensional structure analysis suggests that the D39K mutation disrupted a larger ionic-interaction network on the protein surface, thus preventing the formation of the tetramer.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"757 ","pages":"Article 151610"},"PeriodicalIF":2.5,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143645059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Collagen XII deficiency promotes ligament-specific heterotopic ossification via fibrochondrocyte differentiation

IF 2.5 3区生物学

Biochemical and biophysical research communications Pub Date : 2025-03-11 DOI: 10.1016/j.bbrc.2025.151621

Kei Fujihara , Taiju Yoneda , Akira Sugidono , Yukina Okada , Sakura Hiyama , Shuhei Kajikawa , Yuko Fukunaga , Manuel Koch , Yayoi Izu

{"title":"Collagen XII deficiency promotes ligament-specific heterotopic ossification via fibrochondrocyte differentiation","authors":"Kei Fujihara , Taiju Yoneda , Akira Sugidono , Yukina Okada , Sakura Hiyama , Shuhei Kajikawa , Yuko Fukunaga , Manuel Koch , Yayoi Izu","doi":"10.1016/j.bbrc.2025.151621","DOIUrl":"10.1016/j.bbrc.2025.151621","url":null,"abstract":"<div><div>Heterotopic ossification of tendons and ligaments causes pain and dysfunction, significantly reducing quality of life. However, its underlying mechanisms remain elusive. In addition to injury, tissue organization and stiffness have been implicated in heterotopic ossification. Collagen XII, a member of the fibril-associated collagens with interrupted triple helices (FACIT) family, plays a crucial role in maintaining the structural integrity and function of tendons and ligaments. Its deficiency alters tissue stiffness and predisposes ligaments to rupture. In this study, we investigated whether collagen XII contributes to the development of heterotopic ossification. Three-dimensional microcomputed tomography (3D-μCT) and X-ray analyses revealed heterotopic bone formation in the knee and ankle ligaments, but not in tendons, of <em>Col12a1</em>-deficient mice, with a 100 % incidence in mice older than 19 weeks. Histological analysis showed the presence of Alcian blue- and Toluidine blue-positive fibrochondrocyte-like cells in <em>Col12a1</em>-deficient ligaments, which were subsequently replaced by bone tissue, as indicated by Alizarin red staining. Real-time qPCR analysis of knee ligaments demonstrated a slight increase in chondrogenic markers and a significant upregulation of osteogenic markers in <em>Col12a1</em>-deficient mice compared with wild-type controls. <em>In vitro</em> chondrogenesis and osteogenesis assays using primary tenocytes from wild-type and <em>Col12a1</em>-deficient mice revealed that collagen XII deficiency enhanced osteogenic potential, whereas chondrogenic potential remained comparable. Our findings indicate that collagen XII deficiency specifically induces heterotopic bone formation in knee and ankle ligaments, occurring via fibrochondrocytes rather than through endochondral or intramembranous ossification.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"757 ","pages":"Article 151621"},"PeriodicalIF":2.5,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143627908","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}

引用次数: 0

An integrated approach of transcriptomics, network pharmacology and molecular docking uncovers the mechanisms of 5,6,7,4′-tetramethoxyflavone in treating cervical cancer

IF 2.5 3区生物学

Biochemical and biophysical research communications Pub Date : 2025-03-10 DOI: 10.1016/j.bbrc.2025.151611

Qiang You , Lan Li , Li Liu

{"title":"An integrated approach of transcriptomics, network pharmacology and molecular docking uncovers the mechanisms of 5,6,7,4′-tetramethoxyflavone in treating cervical cancer","authors":"Qiang You , Lan Li , Li Liu","doi":"10.1016/j.bbrc.2025.151611","DOIUrl":"10.1016/j.bbrc.2025.151611","url":null,"abstract":"<div><div>5,6,7,4′-tetramethoxyflavone (TMF), a dietary polymethoxyflavone (PMF) with multifaceted health-promoting benefits, has recently been identified as a potential chemotherapeutic agent for cervical cancer (CCA) in our previous study. Nevertheless, its mechanisms of action involved remain unclear. To address this knowledge gap, we employed an integrative strategy combining transcriptomic profiling, network pharmacology, and molecular docking to systematically investigate TMF's inhibitory effects on HeLa cells. Transcriptomic analysis revealed 1,127 differentially expressed genes (DEGs) in TMF-treated HeLa cells, comprising 765 down-regulated and 362 up-regulated genes. Protein-protein interaction (PPI) network analysis identified 12 hub targets ranked by connectivity: JUN, FN1, VEGFA, FOS, ITGB3, NOTCH1, ESR1, EGF, APP, DLG4, EGR1 and ITGB2. Gene Ontology (GO) enrichment analysis demonstrated significant associations with biological processes including signal transduction, cytoplasm, protein binding, positive regulation of apoptotic cell clearance, t-tubules and extracellular matrix structural constituent conferring tensile strength. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed enrichment in 38 signaling pathways. Molecular docking simulations comfirmed good affinities between TMF and all 12 targets, exhibiting binding energies below −5.0 kcal/mol. Our findings suggest that TMF exerts antitumor activity against HeLa cells through multi-target modulation of critical pathways including Pathway in cancer, FoxO, PI3K-Akt, mTOR, AMPK and apoptosis signaling pathway. While these bioinformatics predictions provide mechanistic insights, experimental validation through q-PCR, western blotting, and surface plasmon resonance remains essential to confirm these findings. This study establishes a foundation for further exploration of TMF's therapeutic potential in CCA management.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"760 ","pages":"Article 151611"},"PeriodicalIF":2.5,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143716313","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}

引用次数: 0