Badria M. Alshehri , Ahmed S. Elshimy , Ahmed M. Salah , Zehbah Ali Mohammed Al-Ahmed , Eder C. Lima , Glaydson S. dos Reis , Ali Q. Selim , Aliaa M. Badawy , Mohamed Mobarak , Moaaz K. Seliem , Hazem I. Bendary
{"title":"Sodium alginate-modified activated binder derived from TiO2 nanoparticles and carbon-rich limestone: A new bio-based composite for methylene blue adsorption","authors":"Badria M. Alshehri , Ahmed S. Elshimy , Ahmed M. Salah , Zehbah Ali Mohammed Al-Ahmed , Eder C. Lima , Glaydson S. dos Reis , Ali Q. Selim , Aliaa M. Badawy , Mohamed Mobarak , Moaaz K. Seliem , Hazem I. Bendary","doi":"10.1016/j.ijbiomac.2025.143848","DOIUrl":"10.1016/j.ijbiomac.2025.143848","url":null,"abstract":"<div><div>Herein, a mixture of naturally carbonized limestone (BL) and rutile nanoparticles (TiO<sub>2</sub>) was modified with sodium alginate (SA) to produce a novel biosorbent (SA-AATiO<sub>2</sub>/BL) for methylene blue (MB) uptake. The physicochemical characterization data suggested a unique SA-AATiO<sub>2</sub>/BL properties rich in surface functionalities with improved adsorptive properties. The adsorption experiments suggested that pseudo-first-order (PFO) and Langmuir models offered the best fit for the kinetic and equilibrium studies, respectively. The maximum adsorption capacity was 263.40 mg/g at 25 °C, and it enhanced to 283.42 mg/g when the temperature increased to 55 °C. The statistical monolayer model's physicochemical parameters were used to understand MB adsorption per functional group, active site density of SA-AATiO<sub>2</sub>/BL interaction energies, and sorption capacities at saturation. Theoretically, the adsorption process across all temperatures involves a multi-molecular adsorption mechanism and vertical positioning. The thermodynamic studies indicated an endothermic and spontaneous adsorption, in which the MB molecules adsorption was governed by physical forces such as hydrogen bonds and electrostatic interactions, with energies ranging from 16.80 to 17.53 kJ/mol. According to the regeneration results of up to six rounds, the SA-AATiO<sub>2</sub>/BL demonstrated stability and suitability for reusing in actual wastewater treatment.</div></div>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":"311 ","pages":"Article 143848"},"PeriodicalIF":7.7,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bang Chen , Shuxin Zheng , Hsihua Wang , Ruixi Yang , Yuting Xiang , Yuqing Huang , Jin Pei , Yang Zhang , Rao Fu
{"title":"Identification of key enzymes participated in the biosynthesis of a rare flavonol patuletin in the medicinal plant Echinacea angustifolia","authors":"Bang Chen , Shuxin Zheng , Hsihua Wang , Ruixi Yang , Yuting Xiang , Yuqing Huang , Jin Pei , Yang Zhang , Rao Fu","doi":"10.1016/j.ijbiomac.2025.143924","DOIUrl":"10.1016/j.ijbiomac.2025.143924","url":null,"abstract":"<div><div>Echinacea species are widely recognized as medicinal herbs producing top-selling herbal supplements in the United States. Instead of the common flavonoids quercetin and kaempferol and their glycosides, a rutinoside of the rare flavonol patuletin has been identified as the predominant flavonoid in the <em>E. angustifolia</em>, an important resource plant for Echinacea. Patuletin features an additional 6-methoxy group on the A ring compared to quercetin. The specific enzymes responsible for flavone 6-hydroxylation and methylation remain elusive. In this study, we constructed a multi-tissue transcriptome of <em>E. angustifolia</em> and screened flavone 6-hydroxylase (F6H) and methyltransferase (OMT)-encoding genes through phylogenetic analysis. Two CYP450 oxidases, EaF6H1 and EaF6H2, from the CYP706X and CYP82D subfamilies, respectively, were identified as possessing F6H activity, along with two CCoAOMTs (EaCCoAOMT1/2) mediating subsequent 6-<em>O</em>-methylation for the biosynthesis of patuletin. The tissue-specific expression patterns, substrate specificity, and molecular docking simulations of these hydroxylases and OMTs were thoroughly investigated. Finally, we successfully reconstructed patuletin biosynthesis in <em>Nicotiana benthamiana</em> leaves using these identified genes. Our results enhance the understanding of the flavonoid biosynthesis pathway and provide synthetic elements for the production of rare flavonoids from the medicinal plant <em>E. angustifolia</em>.</div></div>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":"311 ","pages":"Article 143924"},"PeriodicalIF":7.7,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kanchan A. Jane, Nazma N. Inamdar, Nandkishor R. Kotagale
{"title":"Effect of gelatinizing temperature and moisture on the retrogradation of coix starch","authors":"Kanchan A. Jane, Nazma N. Inamdar, Nandkishor R. Kotagale","doi":"10.1016/j.ijbiomac.2025.143860","DOIUrl":"10.1016/j.ijbiomac.2025.143860","url":null,"abstract":"<div><div>Growing snacking trends are boosting the market demand for pre-gelatinized seed flours and the degree of crystallinity of gelatinized starch could be a useful determinant of shelf life and quality. We investigated the effect of gelatinization temperature on purified coix starch (PCS) and the role of added moisture on retrogradation of gelatinized PCS at different temperatures. Disruption of granular structure of PCS with progressive agglomeration resulted in the formation of gelatinized mass with increasing gelatinizing temperature. Amylose content, hydration, degree of gelatinization (DG) and peak viscosity increased while relative crystallinity and short-range structures decreased with elevated gelatinizing temperature. Retrogradation of PGCS increased crystallinity with reduced hydration, peak viscosity without significant change in flow properties and amylose content. Thermal decomposition of PGCS occurred at lower temperature with elevated gelatinizing temperature. PCS was more resistant to thermal decomposition as compared to PGCS. The degree of crystallization affected by added moisture suggested the disruption of molecular arrangement. Higher moisture levels were required for PGCS with lower DG for crystallinity during retrogradation whereas low moisture levels were needed for PGCS with greater DG. Controlling moisture level seems to be critical for the quality and shelf life of the products derived from gelatinized PCS.</div></div>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":"311 ","pages":"Article 143860"},"PeriodicalIF":7.7,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"IR-MBiTCN: Computational prediction of insulin receptor using deep learning: A multi-information fusion approach with multiscale bidirectional temporal convolutional network","authors":"Farman Ali , Atef Masmoudi , Tamim Alkhalifah , Fahad Alturise , Wajdi Alghamdi , Majdi Khalid","doi":"10.1016/j.ijbiomac.2025.143844","DOIUrl":"10.1016/j.ijbiomac.2025.143844","url":null,"abstract":"<div><div>The insulin receptor (IR) is a transmembrane protein that controls glucose homeostasis and is highly associated with chronic diseases including cancer and neurological. Traditional experimental methods have provided essential insights into IR structure and function, but they are constrained by time, cost, and scalability. To address these limitations, we present a computational technique for IR prediction based on deep learning and multi-information fusion. First, we built sequence-based training and testing datasets. Second, the compositional, word embedding, and evolutionary features were retrieved using the Weighted-Group Dipeptide Composition (W-GDPC), FastText, and Bi-Block-Position Specific Scoring Matrix (BB-PSSM), respectively. Third, we use compositional, word embedding, and evolutionary features to generate multi-perspective fused features (MPFF). Fourth, the Multiscale Bidirectional Temporal Convolutional Network (MBiTCN) is used to train the model to process features at multiscale and analyze sequences in both forward and backward directions. The proposed approach (IR-MBiTCN) outperforms competing deep learning (DL) and machine learning (ML)-based models on training and testing datasets, achieving 83.50 % and 79.43 % accuracy, respectively. This study represents a pioneering use of computational methodology in IR prediction, providing a scalable, efficient alternative to experimental procedures and paving the way for advances in chronic disease therapy and drug discovery.</div></div>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":"311 ","pages":"Article 143844"},"PeriodicalIF":7.7,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Unraveling the unique amyloid-like aggregation behavior of the tumor suppressor p53 mutants in human cancers","authors":"Nisha Manav , Pratibha Sharma , Sankat Mochan , Lakshay Malhotra","doi":"10.1016/j.ijbiomac.2025.143883","DOIUrl":"10.1016/j.ijbiomac.2025.143883","url":null,"abstract":"<div><div>Missense mutations in the tumor suppressor p53 significantly disrupt its native structure and functions, playing a pivotal role in human cancer pathogenesis. Oncogenic mutant p53 (mutp53) not only loses its tumor-suppressive capabilities but also acquires oncogenic functions, driving cancer progression, metastasis, and chemoresistance. Despite extensive research on mutp53, the role of missense mutations in triggering amyloid-like aggregation of p53 remains an underexplored and fascinating area of study.</div><div>To date, over 50 proteins are known to form amyloid-like aggregates due to abnormal folding, resulting in insoluble protein fibrils that contribute to various protein misfolding diseases, including cancer. However, the precise mechanisms by which aggregated proteins induce cancer remain inadequately understood. Notably, certain p53 mutations promote its aggregation, which has emerged as a critical factor in protein aggregation-induced oncogenesis.</div><div>This review delves into the mechanisms underpinning mutp53 aggregation, emphasizing unique properties such as coaggregation, bio-isolation, prion-like cell-to-cell transmission, and chemoresistance promotion. Leveraging diverse in-silico, biophysical, and biochemical approaches, we comprehensively analyzed the aggregating potential of 26 mutp53 variants among 1297 missense mutations identified in human cancers. These findings shed light on the multifaceted roles of mutp53 aggregates in oncogenesis and tumor progression.</div><div>Lastly, we present an integrative exploration of emerging therapeutic strategies designed to disaggregate mutp53 aggregates, offering promising directions for targeted cancer therapy. By addressing this enigmatic aspect of mutp53 biology, our review advances the understanding of protein aggregation in cancer and identifies avenues for innovative therapeutic interventions.</div></div>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":"311 ","pages":"Article 143883"},"PeriodicalIF":7.7,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Optimization of facile synthesis of xanthan gum xanthate based hydrogel for the capturing of heavy metal ions from aqueous solutions","authors":"Arbind Chaurasiya , Poorn Prakash Pande , Ravi Shankar , Prateek Khare , Kopal Kashaudhan","doi":"10.1016/j.ijbiomac.2025.143594","DOIUrl":"10.1016/j.ijbiomac.2025.143594","url":null,"abstract":"<div><div>This study investigated the elimination of Co<sup>2+</sup>, Ni<sup>2+</sup> and Cu<sup>2+</sup> ions from water using a mesoporous, cost-effective, reusable, biodegradable and efficient xanthan gum xanthate-based hydrogel (XGmXHs hydrogel) as an adsorbent. The XGmXHs hydrogel was prepared via free radical polymerization process with varying the ratios of 2-hydroxyethyl methacrylate (HEMA) and acrylic acid (AA) as monomers. These ratios were optimized based on grafting efficiency, swelling capacity and point of zero charge (ΔpH<sub>PZC</sub>) analysis. The results demonstrate that the XGmXHs hydrogel containing copolymer of HEMA: AA in a 1:3 ratio is optimal for grafting on xanthan gum (XGm) during polymerization process. The 1:3 ratio of monomer grafted on xanthan gum xanthate (XGmX) is referred to as XGmXHs-3 hydrogel. The XGmXHs-3 hydrogel showed a consistently negative surface charge across a diverse pH range, resulting the AA content was enhanced. Consequently, the swelling and adsorption capacity of the XGmXHs-3 hydrogel is significantly high. The optimum swelling capacity of the XGmXHs-3 hydrogel was found 40,128 % in water at pH 11. The maximum removal efficiency was 92.21 % for Co<sup>2+</sup>, 95.45 % for Ni<sup>2+</sup> and 98.30 % for Cu<sup>2+</sup> ions at pH 7. According to isothermal studies, the adsorption data aligns most closely with Langmuir isotherm model, resulting the adsorption capacities of 358.42, 469.48 and 555.55 mg/g Co<sup>2+</sup>, Ni<sup>2+</sup> and Cu<sup>2+</sup> ions, respectively. The adsorption kinetics were consistent with a pseudo-first-order kinetic model, showing rate constant of −2.6 × 10<sup>−2</sup>, −4.0 × 10<sup>−2</sup> and − 6.3 × 10<sup>−2</sup> min<sup>−1</sup> for Co<sup>2+</sup>, Ni<sup>2+</sup> and Cu<sup>2+</sup> ions, respectively. The desorption efficiencies were 64.76 % for Co<sup>2+</sup>, 68.83 % for Ni<sup>2+</sup> and 72.11 % for Cu<sup>2+</sup> ions to the XGmXHs-3 hydrogel after being regenerated for the fifth cycle.</div></div>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":"311 ","pages":"Article 143594"},"PeriodicalIF":7.7,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaochan Wang , Tao Lin , Yihan Lin , Chang Xu , Kai Ma , Changliang Zhang , Feng Ji , Ghahvechi Chaeipeima Mahsa , Xin Rui , Wei Li
{"title":"Chemical composition and in vitro intestinal probiotic properties analysis of exopolysaccharides from screened Streptococcus thermophilus 90301","authors":"Xiaochan Wang , Tao Lin , Yihan Lin , Chang Xu , Kai Ma , Changliang Zhang , Feng Ji , Ghahvechi Chaeipeima Mahsa , Xin Rui , Wei Li","doi":"10.1016/j.ijbiomac.2025.143882","DOIUrl":"10.1016/j.ijbiomac.2025.143882","url":null,"abstract":"<div><div>A strain of <em>Streptococcus thermophilus</em> 90301, characterized by robust growth and high exopolysaccharide (EPS) production, was selected. Following isolation and purification, two EPS components, EPS-1 and EPS-2, were obtained. The analysis revealed that EPS-1 was composed of mannose, rhamnose, glucosamine, glucose, and galactose with molar ratios of 0.94:0.09:0.11:1.00:0.16, whereas EPS-2 was composed of mannose, ribose, glucose, and galactose with molar ratios of 15.11:0.26:1.00:0.38; respectively. The average molecular weights were determined to be 2.31 × 10<sup>5</sup> Da for EPS-1 and 2.41 × 10<sup>5</sup> Da for EPS-2. Furthermore, the prebiotic potential of the two fractions (EPS-1 and EPS-2) was investigated through <em>in vitro</em> simulation of human fecal fermentation digestion. Both EPS-1 and EPS-2 were not digested by the digestive fluids and were able to significantly modulate the composition of the gut microbiota. Additionally, they enhanced the gut microbiota's ability to produce short-chain fatty acids. These findings provide some basis for the functional application of polysaccharide components extracted from <em>S. thermophilus</em> 90301 as a potential prebiotic.</div></div>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":"311 ","pages":"Article 143882"},"PeriodicalIF":7.7,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The role of biological macromolecules in the regulation of angiogenesis in glioblastoma: Focus on vascular growth factors, integrins, and extracellular matrix proteins","authors":"Abbas Zabihi","doi":"10.1016/j.ijbiomac.2025.143838","DOIUrl":"10.1016/j.ijbiomac.2025.143838","url":null,"abstract":"<div><div>Glioblastoma, classified as a grade 4 brain tumor, accounts for approximately half of all malignant central nervous system cancers. Despite extensive research and aggressive treatment modalities, much about this disease remains elusive. The proliferation of blood vessels within glioblastoma tumors significantly contributes to their invasive nature, primarily due to the influence of vascular endothelial growth factor-A (VEGF-A). As a result, the past decade has seen a concentrated effort to explore angiogenesis, especially the VEGF signaling pathway, as a therapeutic target for glioblastoma. This investigation led to the FDA approval of bevacizumab, a monoclonal antibody against VEGF-A, for the treatment of recurrent glioblastoma. However, despite promising clinical trials and theoretical research, bevacizumab has not significantly improved patient survival rates. Furthermore, other anti-angiogenic agents targeting the VEGF signaling pathway have shown limited efficacy. This suggests the existence of multiple alternative angiogenic pathways that facilitate vascularization, even when VEGF signaling is inhibited.</div><div>In this study, we aim to assess the current landscape of anti-angiogenic agents, explore potential resistance mechanisms to such therapies, and suggest strategies to improve the effectiveness of these therapeutic interventions. Our goal is to provide a comprehensive understanding of the limitations of current treatments and to identify new avenues for enhancing therapeutic outcomes in glioblastoma patients.</div></div>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":"311 ","pages":"Article 143838"},"PeriodicalIF":7.7,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A dual-peptides and specific promoter-modified nano gene delivery system for myocardial hypertrophy treatment","authors":"Yangchen Xing , Lu Zhou , Yuxin Chen , Qianyu Zhang , Xianwei Wu , Zongjie Gan , Kexin Wu , Dongjun Jiang , Shiqi Wei , Huali Chen","doi":"10.1016/j.ijbiomac.2025.143759","DOIUrl":"10.1016/j.ijbiomac.2025.143759","url":null,"abstract":"<div><div>Cardiac hypertrophy represents the heart's adaptive response to physiological or pathological stimuli, functioning to alleviate ventricular wall stress and preserve cardiac function and efficiency. However, pathological hypertrophy usually progresses to heart failure. Gene therapy, in contrast to conventional chemotherapeutic drugs, has the ability to impact cardiac hypertrophy directly, while the lack of adequate vectors limits its application. Gemini surfactants (GS) have been proven to be effective for transfection in vivo in earlier research. To diminish the natural liver targeting of GS nanoparticles, a dual-targeted myocardial biomimetic GS nanocomplex gene delivery system with functional peptides TAT and PCM modified and synergized with cardiac-specific promoter chicken cardiac troponin T promoter (cTnT) is designed in this study. Bioluminescence imaging reveals the utility of targeting hypertrophy myocardium, resulting in low localization in the liver upon systemic administration. Biochemical indicators, echocardiography, gross morphology and histology all indicate that GS-nanocomplexes attenuate ISO-induced cardiac hypertrophy. RNA sequencing results reflect different uptake pathways for different GS nanocomplexes, and the investigation of cellular uptake under various endocytosis inhibitors demonstrate that clathrin-mediated endocytosis (CME) serves as the primary endocytic pathway for GS-pDNA uptake and caveolin-mediated endocytosis (CVME) serves as the primary endocytic pathway for GS-pDNA-TP-RBCM uptake. The endocytic pathway for nanocomplexes is confirmed by CAV-1 silencing. In summary, this research presents a dual myocardium-targeted biomimetic GS nanocomplex for gene delivery for cardiomyocytes. The in vivo and in vitro targeting ability, good biocompatibility and helpful therapeutic efficacy for cardiac hypertrophy are verified, and the uptake mechanism and intracellular transport pathway of GS nanocomplex are revealed. This innovative approach provides a promising therapeutic strategy for the treatment of cardiac hypertrophy.</div></div>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":"311 ","pages":"Article 143759"},"PeriodicalIF":7.7,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mingyu Bai , Zelin Sang , Yang Cui , Huicong Feng , Yu Liu , Zhen Dai , Zipeng Zhou , Xifan Mei , Haosen Zhao
{"title":"Multi-omics analysis identified and confirmed TNF-α as a key initiator of the inflammatory response following spinal cord injury","authors":"Mingyu Bai , Zelin Sang , Yang Cui , Huicong Feng , Yu Liu , Zhen Dai , Zipeng Zhou , Xifan Mei , Haosen Zhao","doi":"10.1016/j.ijbiomac.2025.143866","DOIUrl":"10.1016/j.ijbiomac.2025.143866","url":null,"abstract":"<div><div>Spinal cord injury (SCI) is a complex central nervous system (CNS) trauma that triggers multifaceted immune responses. In recent years, zinc has garnered considerable attention for its beneficial roles in anti-apoptosis and the attenuation of oxidative stress. However, the regulatory mechanisms by which zinc influence post-SCI immune-inflammatory responses remain insufficiently understood. In this study, we employed a multi-omics approach, combining transcriptomics, metabolomics, and single-cell RNA sequencing, to elucidate the mechanisms through which zinc ions modulate immune responses in injured spinal cord tissues. Our results demonstrate that zinc ions significantly regulate the expression of TNF-α signaling molecules. By inhibiting the TNF-α signaling pathway, zinc ions effectively mitigate apoptosis and reduce immune-inflammatory responses following SCI. Furthermore, through the integration of human and murine immune cell atlases, we performed a cluster analysis of key immune cell populations and constructed an immunological landscape of spinal cord tissues post‑zinc ion treatment. Notably, we identified microglia, key CNS immune cells, as exerting a strong anti-inflammatory effect by suppressing their TNF-α signaling activity. This study not only sheds light on the pivotal immune-inflammatory regulatory mechanisms of TNF-α signaling in zinc ion-mediated SCI therapy but also provides valuable theoretical and experimental insights for advancing preclinical research on SCI.</div></div>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":"311 ","pages":"Article 143866"},"PeriodicalIF":7.7,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}