International Journal of Biological Macromolecules最新文献

{"title":"CASK promotes prostate cancer progression via kinase-dependent activation of AKT","authors":"Varsha Rathore ,&nbsp;Ching-Yuan Cheng ,&nbsp;Shao-Peng Chen ,&nbsp;Chia-Yee Lin ,&nbsp;Chuang-Rung Chang ,&nbsp;Wan-Wan Lin","doi":"10.1016/j.ijbiomac.2025.143965","DOIUrl":"10.1016/j.ijbiomac.2025.143965","url":null,"abstract":"<div><div>Until now, the role of calcium/calmodulin-dependent serine protein kinase (CASK) in prostate cancer (PCa) progression remains unknown. In this study, we investigated the roles of CASK in PCa progression, cell migration, and invasion. We found that CASK is up-regulated in PCa tissues of patients. Lentivirus-based CASK silencing does not affect cell growth or serum-free-induced cell death in PC3 and LNCaP cells, regardless of the presence or absence of TGF-β. CASK silencing decreases cell migration and invasion, either in the absence or presence of TGF-β stimulation. Immunoblotting data indicate that CASK silencing does not alter TGF-β-induced Smad2/3 and ERK phosphorylation but reduces TGF-β-induced AKT phosphorylation. To understand the roles of AKT and CaMK-like activity of CASK in cellular responses in PCa cells, we treated cells with AKT inhibitor and specific kinase inhibitors of CASK (NR162) and CaMKII (KN-93). We found that these agents can inhibit cell invasion and migration. In addition, NR162 and KN-93 also reduce TGF-β-induced AKT phosphorylation. Moreover, the co-immunoprecipitation data indicate the association between CASK and AKT. In HEK293 cells overexpressing system, we further found that CASK can enhance AKT S473 phosphorylation. The tumorigenic effect of CASK is confirmed in the xenograft mouse system. In summary, CASK is a promoter of PCa progression and can enhance PCa cell migration and invasion via kinase-dependent AKT activation independent of TGF-β-induced Smad2/3 and ERK signaling.</div></div>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":"311 ","pages":"Article 143965"},"PeriodicalIF":7.7,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906137","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":"Bio-inspired eco-friendly wheat gluten based underwater adhesives with instant, robust and harsh environment adhesion properties","authors":"Haohan Ge ,&nbsp;Jing Chen ,&nbsp;Lanting Yu ,&nbsp;Xian Liu ,&nbsp;Liang Zhang ,&nbsp;Qiang Gao ,&nbsp;Peizhi Zhu ,&nbsp;Chunxia Gao","doi":"10.1016/j.ijbiomac.2025.143925","DOIUrl":"10.1016/j.ijbiomac.2025.143925","url":null,"abstract":"<div><div>Underwater adhesives are essential in industry, biomedical field, as well as our daily life. Herein, inspired by the natural plant protein, an eco-friendly, cost-effective and renewable bio-resources gliadin/TA adhesive was developed by a facile and effective strategy. The prepared gliadin/TA adhesive displayed exceptional substrate universality, rapid self-healing ability, instant and long-term underwater adhesion, strong affinity and good environmental adaptability. In the dry environment, the glued woods with a lab-shear bond can lift a weight of 11.62 kg object with a bond area was 2.15 cm². In the water, the gliadin/TA adhesives can successfully lift 1 kg stainless steel and maintained effective adhesion for up to 50 days without detachment. Meanwhile, the gliadin/TA adhesives exhibited excellent environmental adaptability, including 1 M NaCl, extreme acidic (pH = 2), alkaline (pH = 14) and high-temperature (48 °C) aqueous solutions. Additionally, the potential applications of gliadin/TA adhesives have been proved by repairing porcine skin and bones, bonding wood particles together rapidly to withstand water-flushing, plugging leaky containers and broken pig intestine. This work presents a distinctive and facile strategy for designing and developing the eco-friendly, cost-effective and renewable bio-resources underwater adhesives.</div></div>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":"311 ","pages":"Article 143925"},"PeriodicalIF":7.7,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906347","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":"Novel pH-responsive folate conjugated chitosan and thiolated carboxymethyl cellulose based nanoparticles: potential approach for site-specific targeting in colon cancer treatment","authors":"Hanasul Hanan ,&nbsp;Fahad Pervaiz ,&nbsp;Muhammad Ijaz ,&nbsp;Tahreem Arshad ,&nbsp;Komal Saeed ,&nbsp;Syeda Munazza Javaid ,&nbsp;Pakeeza Hussain ,&nbsp;Asma Majeed","doi":"10.1016/j.ijbiomac.2025.143952","DOIUrl":"10.1016/j.ijbiomac.2025.143952","url":null,"abstract":"<div><div>The study objective was to develop folate decorated chitosan (CHT-FA) by the carbodiimide-mediated process to utilize the overexpressed folate receptors in the treatment of colon cancer. The substitution degree of FA to CHT was 1.4 %. FTIR and H¹NMR ensured the successful conjugation of FA with CHT. Thermal analysis and XRD demonstrated the thermal stability and amorphous nature of CHT-FA after conjugation. Thiolation of carboxymethyl cellulose, having a 1612.35 μmol/g thiol group, was achieved via oxidation followed by reductive amination. CHT-FA and thiolated carboxymethyl cellulose (CMC-SH) were utilized in the development of nanoparticles with eudragit S100 coating (EU-FU-CHT-FA/CMC-SH NPs) for targeted delivery to the colon. The fabricated NPs demonstrated a higher release pattern at 7.4 pH after &lt;5 % release at 1.2 pH. CHT-FA/CMC-SH NPs showed enhanced mucoadhesion time by up to 237 min. Furthermore, compared to the FU solution, the MTT analysis showed that FU-CHT-FA/CMC-SH NPs had a more cytotoxic effect and increased cellular uptake in the Caco-2 cell line via the folate receptor-facilitated endocytosis process along with the consequence of thiolation which prevents closer of tight junction, resulting in enhanced cellular absorption. These findings support the potential of the developed NPs as a tumor-targeted therapeutic delivery.</div></div>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":"311 ","pages":"Article 143952"},"PeriodicalIF":7.7,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906138","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":"In vitro assessment of the effect of Porphyra haitanensis polysaccharides on the intestinal flora of allergic mice","authors":"Peilin Chen ,&nbsp;YuShan Huang ,&nbsp;Hongliang Zeng ,&nbsp;Mingjing Zheng ,&nbsp;Juanjuan Guo","doi":"10.1016/j.ijbiomac.2025.143950","DOIUrl":"10.1016/j.ijbiomac.2025.143950","url":null,"abstract":"<div><div>This study systematically investigated the modulatory effects of <em>Porphyra haitanensis</em> polysaccharides (PHP) and its two <em>P. haitanensis</em> polysaccharide components (PHP40 and PHP80) on gut microbiota in ovalbumin (OVA)-sensitized mice <em>via in vitro</em> fermentation. PHP40 and PHP80 exhibited sulfate contents of 5.94 ± 0.05 % and 11.72 ± 0.03 %, respectively, with galactose and glucose as dominant monosaccharides. The different polysaccharide components had different effects on the aforementioned changes in the species composition and structure of the gut microbiota in allergic mice, with distinct dominant microbial profiles across groups. PHP could promote <em>Bacillus</em> and <em>Enterococcus</em> proliferation while inhibiting <em>Staphylococcus</em>. PHP40 and PHP80 could promote <em>Enterococcus</em> and <em>Enterobacter</em> growth but suppressed <em>Staphylococcus</em> and <em>Bacillus</em>. Functional prediction indicated PHP significantly improved galactose metabolism and primary/secondary bile acid biosynthesis, potentially alleviating allergic responses.</div></div>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":"311 ","pages":"Article 143950"},"PeriodicalIF":7.7,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906139","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":"Water-based green media for the synthesis of cellulose acid half-esters: physicochemical characterization and conformation-modulating interactions","authors":"Nafea Achalhi ,&nbsp;Youssef El Ouardi ,&nbsp;Ridouan El Yousfi ,&nbsp;Ayoub Abarkan ,&nbsp;Soufian El Barkany ,&nbsp;Abderrahman El Idrissi","doi":"10.1016/j.ijbiomac.2025.143968","DOIUrl":"10.1016/j.ijbiomac.2025.143968","url":null,"abstract":"<div><div>This study presents a simple and ecofriendly pathway for synthesizing of cellulose acid half-esters, utilizing a toxic organic solvent-free synthesis strategy and ensuring a green approach. The esterification of hydroxyethyl cellulose (HEC), derived from <em>Stipa tenacissima</em>, with maleic, succinic, and phthalic anhydrides was investigated, revealing significant structural and physicochemical modifications. Increasing the anhydride/HEC molar ratio enhanced the degree of substitution (DS), reaching values of 1.4, 1.28, and 0.51 for HEC-AS, HEC-AM, and HEC-AP, respectively. High reaction temperatures (&gt;100 °C) promoted cross-linking, affecting the solubility of the modified polymers. Structural analysis showed that the organization of acid half-esters strongly influenced wetting properties and thermal behavior. HEC-AM and HEC-AP exhibited lower <em>T</em>_<em>g</em> values (40 °C and 91.82 °C) due to hydrogen bonding reorganization and the resulted configuration of the acid half-ester groups, while HEC-AS remained stable at 117.76 °C. These structural differences resulted in distinct contact angles of 55°, 90°, and 102°, respectively. Solubility and surface charge studies further confirmed the impact of modification on polymer charge behavior, resulting in an anionic character. These findings demonstrate the effectiveness of this green synthesis strategy in tailoring biopolymer properties for functional applications.</div></div>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":"311 ","pages":"Article 143968"},"PeriodicalIF":7.7,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143907061","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":"PtrCWINV3 encoding a cell wall invertase regulates carbon flow to wood in Populus trichocarpa","authors":"Shuang Zhang ,&nbsp;Yuanzhi Yang ,&nbsp;Ruhui Chang ,&nbsp;Shiqi Yao ,&nbsp;Fengbo Xue ,&nbsp;Zhaoyin Hou ,&nbsp;Guanjun Liu ,&nbsp;Zhiru Xu","doi":"10.1016/j.ijbiomac.2025.143891","DOIUrl":"10.1016/j.ijbiomac.2025.143891","url":null,"abstract":"<div><div>Cell wall invertase (CWINV) catalyzes the hydrolysis of sucrose into glucose and fructose in the apoplastic unloading pathway, with carbon sources provided for sink tissues. However, its role in wood formation remains undetermined. Therefore, transgenic lines overexpressing <em>PtrCWINV3</em> or with knocked-out <em>PtrCWINV3</em> expression were generated in <em>Populus trichocarpa</em>. Compared with wild type, the <em>PtrCWINV3</em>-knockout lines showed decreased CWINV activity (by 7.4 %–10.8 %), which resulted in a 1.5 %–1.8 % decrease in cellulose content, a 0.82 %–0.98 % decrease in hemicellulose content, and an increase in lignin content (by 2.9 %–4.7 %). These changes in structural carbohydrate contents were accompanied with anomalies in the late stages of secondary xylem development, characterized by reduced width of the secondary xylem, fewer cell layers in secondary xylem, and thinner fiber cell walls. The lines overexpressing <em>PtrCWINV3</em> under the control of the DX15 promoter in the developing xylem showed the opposite phenotype. Transcriptome data from the developing xylem indicated that <em>PtrCWINV3</em> regulated the expression of genes involved in the biosynthesis of cellulose (<em>CesA</em>, <em>EG</em>, and <em>CB</em>), hemicellulose/pectin (<em>UGD</em>, <em>AXS</em>, <em>GATL</em>, <em>UAM</em>, <em>PAE</em>, and <em>GAUT</em>), and starch (<em>GBSS</em>), which suggested its involvement in multiple polysaccharide metabolic pathways. Ultimately, this facilitated the synthesis of structural carbohydrate components such as cellulose and hemicellulose, which promoted the later stages of secondary xylem development. These findings not only demonstrate the significant role of CWINV activity in wood formation, but also highlight an excellent candidate gene for breeding new poplar varieties with high cellulose and low lignin contents.</div></div>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":"311 ","pages":"Article 143891"},"PeriodicalIF":7.7,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143907063","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":"Influence of the hydrophobic polyhydroxyethyl methacrylate branches grafted with high amylose corn starch on the properties of its electrospun drug-loaded membranes","authors":"Xun Zhang ,&nbsp;Yujie Wu ,&nbsp;Yingfeng Wang ,&nbsp;Maoli Yin ,&nbsp;Zhenzhen Xu ,&nbsp;Feng Liu ,&nbsp;Wei Li","doi":"10.1016/j.ijbiomac.2025.143962","DOIUrl":"10.1016/j.ijbiomac.2025.143962","url":null,"abstract":"<div><div>The nanofiber membranes based on native starch are prone to swelling or dissolution after contact with water, and the fragile starch membranes, due to the aging of molecular chains, are unsuitable for medical dressings. Herein, the hydrophobic polyhydroxyethyl methacrylate (PHEMA) branches in different ratios were grafted onto high amylose corn starch (HACS) using a redox system. Furthermore, electrospun aspirin-loaded nanofiber membranes were prepared and investigated in terms of porosity, swelling capacity, water vapor transmittance rate (WVTR), cumulative release rate, and cytotoxicity. The results confirmed that with increasing grafting ratio, the porosity and WVTR of the HACS<em>-g-</em>PHEMA drug-loaded membrane gradually increased, while swelling capacity slightly decreased from 746.2% to 619.9%, and the cumulative release rate decreased from 56.21% to 32.54% in 2 h. The Ritger-Peppas mathematical model fitting found that the diffusion coefficients of drug-loaded membranes were less than 0.45, which belonged to the Fick diffusion behavior. After the grafting of PHEMA branches, the hydrophobic interaction between starch molecular chains and aspirin was enhanced, and the nanofiber membrane defects were alleviated while still maintaining good biocompatibility. This study provides a foundation for the sustained release of hydrophobic drugs in starch-based medical dressings.</div></div>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":"311 ","pages":"Article 143962"},"PeriodicalIF":7.7,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143907066","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":"Identification, evolution, functional characterization and expression pattern of a fatty acyl desaturase (fads1) gene in Chinese sturgeon (Acipenser sinensis)","authors":"Haoze Ding ,&nbsp;Kan Xiao ,&nbsp;Zhengyong Wen ,&nbsp;Bo Li ,&nbsp;Xin Zhu ,&nbsp;Jing Yang ,&nbsp;Wei Jiang ,&nbsp;Yuanjin Yang ,&nbsp;Shuqi Wang ,&nbsp;Yang Li","doi":"10.1016/j.ijbiomac.2025.143664","DOIUrl":"10.1016/j.ijbiomac.2025.143664","url":null,"abstract":"<div><div>Fatty acyl desaturases (Fads) are known to play critical roles in the biosynthesis of long-chain polyunsaturated fatty acids (LC-PUFAs) in fish species. To date, research on Fads in fish has predominantly focused on Fads2, while studies on Fads1 have been rarely reported. Acipenseriformes, commonly known as Chondrostei, are an ancient fish lineage with unique evolutionary history. However, the biological roles and evolutionary status of Fads1 in Chondrostei remain unclear, which constrains our understanding of the evolutionary processes shaping LC-PUFA biosynthesis in this lineage. In this study, we identified and characterized a <em>fads1</em> gene from Chinese sturgeon (<em>Acipenser sinensis</em>), a critically endangered Chondrostei, using molecular cloning and multiple bioinformatic analyses. The spatio-temporal expression patterns, functional characteristics, and transcriptional regulation in response to dietary fatty acids were investigated. The coding sequence of the <em>fads1</em> gene was 1317 bp in length, encoding a protein of 438 amino acids. Bioinformatic analyses suggested high conservation of <em>fads</em> genes across Chondrostei despite their complex evolutionary history. Functional characterization in yeast showed that Chinese sturgeon Fads1 exhibited Δ5 desaturation activity, efficiently converting 20:3n-6 to arachidonic acid (ARA) and 20:4n-3 to eicosapentaenoic acid (EPA). Fatty acid composition analysis indicated that Chinese sturgeon could biosynthesize LC-PUFAs when they are deficient in their diets. Taken together, these results suggest that <em>fads1</em> plays a crucial role in LC-PUFA biosynthesis in Chinese sturgeon, which provides solid theoretical basis for dietary LC-PUFA requirement of Chinese sturgeon. Furthermore, our findings provide novel insights into evolutionary diversification of <em>fads</em> genes in fish species.</div></div>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":"311 ","pages":"Article 143664"},"PeriodicalIF":7.7,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906354","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 clean high-concentration chlorine dioxide bleaching process at room temperature facilitating the rapid degradation of lignin and its kinetic","authors":"Xiao Zhao,&nbsp;Baojie Liu,&nbsp;Hao Xu,&nbsp;Chengrong Qin,&nbsp;Shuangquan Yao,&nbsp;Chen Liang,&nbsp;Shuangfei Wang","doi":"10.1016/j.ijbiomac.2025.143966","DOIUrl":"10.1016/j.ijbiomac.2025.143966","url":null,"abstract":"<div><div>Elemental Chlorine-Free (ECF) bleaching is a globally prevalent pulping technology that primarily utilizes chlorine dioxide (ClO₂) as a bleaching agent. However, the chlorination side reactions during ECF bleaching lead to the formation of chlorinated adsorbable organic halides (AOX), which are difficult to degrade and pose a potential threat to the ecological environment. This study presents a novel high-concentration ClO₂ pulping bleaching technology at room temperature, which effectively suppresses the chlorination side reactions through the strong oxidizing properties of high-concentration ClO₂, thereby achieving both bleaching and a reduction in AOX generation. The results indicate that high concentrations of ClO₂ efficiently removed residual lignin from the pulp, promoted the cleavage of lignin ether bonds, and had no adverse impact on the strength or crystalline structure of the cellulose. The amount of AOX was effectively controlled to 0.41 kg/t pulp. Kinetic analysis demonstrated that the degradation of lignin in this bleaching system follows first-order reaction kinetics, with an activation energy of 1310.78 J/mol. Approximately 95 % recovery of the ClO₂ solution was achieved through a four-step reabsorption method. This technology advances the development of pulping and bleaching techniques and provides theoretical guidance for the innovation of cleaner pulping and papermaking technologies.</div></div>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":"311 ","pages":"Article 143966"},"PeriodicalIF":7.7,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143907067","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":"Matrix metalloproteinase-9 (MMP-9): A macromolecular mediator in CNS infections: A review","authors":"Mohamad Mosa Mubarak ,&nbsp;Ishfaq Ahmad Baba ,&nbsp;Zubair Ahmad Wani ,&nbsp;Hadiya Amin Kantroo ,&nbsp;Zahoor Ahmad","doi":"10.1016/j.ijbiomac.2025.143902","DOIUrl":"10.1016/j.ijbiomac.2025.143902","url":null,"abstract":"<div><div>Matrix metalloproteinase-9 (MMP-9) is a macromolecular zinc-dependent endopeptidase that plays a critical role in the pathogenesis of Central Nervous System (CNS) infections by modulating extracellular matrix remodelling and blood-brain barrier (BBB) dynamics. This review elucidates the structural and functional properties of MMP-9, highlighting its distinct domain architecture that enables substrate specificity and regulatory mechanisms. MMP-9-mediated BBB disruption is a hallmark of bacterial, viral, fungal, and parasitic CNS infections, facilitating immune cell infiltration and pathogen entry while exacerbating neuroinflammation and tissue damage. Elevated MMP-9 levels in cerebrospinal fluid (CSF) correlate with disease severity, suggesting its potential as a diagnostic biomarker. Advances in therapeutic strategies targeting MMP-9, including small molecule inhibitors, monoclonal antibodies, and peptide-based therapies, demonstrate promising results in mitigating BBB disruption and neuroinflammation. This comprehensive review underscores the dual role of MMP-9 as both a biomarker and therapeutic target, advocating for its inclusion in adjunctive treatment regimens to improve outcomes in CNS infections. Future research should focus on refining MMP-9 inhibitors for clinical use, ensuring specificity, and minimizing off-target effects to harness its full therapeutic potential.</div></div>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":"311 ","pages":"Article 143902"},"PeriodicalIF":7.7,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906575","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}