Pub Date : 2024-11-04DOI: 10.1016/j.ijbiomac.2024.137251
Yuanyi Shao, Bingnan Mu, Xiaoqing Yu, Lan Xu, Renuka Dhandapani, Yiqi Yang
We report a green, non-destructive, and highly effective extraction, dissolution, film casting and solidification technology for cottonseed proteins from cottonseed meals. Although cottonseed meals are protein-rich, with about 40 % of proteins, they are cheap with a price 20 % to 50 % lower than soybean meals due to their poor performance as feed and bioplastics and due to the limited efforts from the academia and industries. Our green and protective protein extraction technology provided an extraction yield of 89 % and purity of 92 % with minimal destruction to the protein backbones, better than those reported previously. Our green dissolution/casting technology provided proteins with maximized unfolding and entanglement. When cottonseed proteins were solidified to form bioplastics, our technology also enabled substantial recovery of cystine crosslinkages between protein molecules to maximize the properties of the final products. Using our technologies, cottonseed protein films from cottonseed meals have toughness higher than what have been reported in literature without adding plasticizers or reinforcement materials, therefore better property stability or shelf life. Our technology is also cost-effective and can potentially add values to the cotton industry.
{"title":"Cottonseed proteins from meals with high yield for plasticizer-free biofilms with good mechanical properties.","authors":"Yuanyi Shao, Bingnan Mu, Xiaoqing Yu, Lan Xu, Renuka Dhandapani, Yiqi Yang","doi":"10.1016/j.ijbiomac.2024.137251","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2024.137251","url":null,"abstract":"<p><p>We report a green, non-destructive, and highly effective extraction, dissolution, film casting and solidification technology for cottonseed proteins from cottonseed meals. Although cottonseed meals are protein-rich, with about 40 % of proteins, they are cheap with a price 20 % to 50 % lower than soybean meals due to their poor performance as feed and bioplastics and due to the limited efforts from the academia and industries. Our green and protective protein extraction technology provided an extraction yield of 89 % and purity of 92 % with minimal destruction to the protein backbones, better than those reported previously. Our green dissolution/casting technology provided proteins with maximized unfolding and entanglement. When cottonseed proteins were solidified to form bioplastics, our technology also enabled substantial recovery of cystine crosslinkages between protein molecules to maximize the properties of the final products. Using our technologies, cottonseed protein films from cottonseed meals have toughness higher than what have been reported in literature without adding plasticizers or reinforcement materials, therefore better property stability or shelf life. Our technology is also cost-effective and can potentially add values to the cotton industry.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589447","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}
Pub Date : 2024-11-04DOI: 10.1016/j.ijbiomac.2024.137266
Wenli Zhao, Yuedong Shen, Yangguang Bao, Óscar Monroig, Tingting Zhu, Peng Sun, Douglas R Tocher, Qicun Zhou, Min Jin
With the increasing use of high-fat diets (HFD), fatty liver disease has become common in fish, and fucoidan is of interest as a natural sulfated polysaccharide with lipid-lowering activity. To explore the molecular regulatory mechanisms of fucoidan's alleviation of HFD-induced lipid deposition in liver, black seabream (Acanthopagrus schlegelii) was used to construct in vivo and in vitro HFD models. In vivo HFD stimulated the protein kinase RNA-like endoplasmic reticulum kinase (Perk) pathway, and up-regulated proliferator-activated receptor gamma (Pparγ) nuclear translocation and expression of lipogenic genes, while it down-regulated Ppar alpha (Pparα) nuclear translocation and expression of lipolytic genes. However, fucoidan reversed these effects of HFD and significantly alleviated HFD-induced lipid accumulation in liver. Moreover, after sirtuin 1 (sirt1) knockdown, these effects of fucoidan disappeared. In the in vitro HFD model, GSK2606414 (GSK)-specific inhibition of the Perk pathway, decreased Pparγ nuclear translocation and increased Pparα nuclear translocation. Overall, fucoidan mitigated HFD-induced, Perk pathway-mediated lipid deposition in the liver of black seabream by activating Sirt1. The findings provided a new prospect for the application of green polysaccharides in aquatic animal feeds.
{"title":"Fucoidan alleviates hepatic lipid deposition by modulating the Perk-Eif2α-Atf4 axis via Sirt1 activation in Acanthopagrus schlegelii.","authors":"Wenli Zhao, Yuedong Shen, Yangguang Bao, Óscar Monroig, Tingting Zhu, Peng Sun, Douglas R Tocher, Qicun Zhou, Min Jin","doi":"10.1016/j.ijbiomac.2024.137266","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2024.137266","url":null,"abstract":"<p><p>With the increasing use of high-fat diets (HFD), fatty liver disease has become common in fish, and fucoidan is of interest as a natural sulfated polysaccharide with lipid-lowering activity. To explore the molecular regulatory mechanisms of fucoidan's alleviation of HFD-induced lipid deposition in liver, black seabream (Acanthopagrus schlegelii) was used to construct in vivo and in vitro HFD models. In vivo HFD stimulated the protein kinase RNA-like endoplasmic reticulum kinase (Perk) pathway, and up-regulated proliferator-activated receptor gamma (Pparγ) nuclear translocation and expression of lipogenic genes, while it down-regulated Ppar alpha (Pparα) nuclear translocation and expression of lipolytic genes. However, fucoidan reversed these effects of HFD and significantly alleviated HFD-induced lipid accumulation in liver. Moreover, after sirtuin 1 (sirt1) knockdown, these effects of fucoidan disappeared. In the in vitro HFD model, GSK2606414 (GSK)-specific inhibition of the Perk pathway, decreased Pparγ nuclear translocation and increased Pparα nuclear translocation. Overall, fucoidan mitigated HFD-induced, Perk pathway-mediated lipid deposition in the liver of black seabream by activating Sirt1. The findings provided a new prospect for the application of green polysaccharides in aquatic animal feeds.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589481","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}
Pub Date : 2024-11-04DOI: 10.1016/j.ijbiomac.2024.137178
June Chelyn Lee, Shogo Urakami, Hiroshi Hinou
Escherichia coli O111 serotype is a critical pathogenic E. coli strain that causes severe, potentially fatal complications. Despite its reported variation, only one structure of the O-antigen polysaccharide from E. coli O111 has been reported. Here, a substructure of the O-antigen from E. coli O111 was characterized using matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry and NMR analysis. MALDI glycotyping revealed differing O-antigen repeating unit masses of Δm/z 787 and 828 in the E. coli strains and lipopolysaccharides from the O111 serogroup. This variation was caused by the replacement of the hexose residue with hexosamine in the repeating units, which was further confirmed by LIFT-TOF/TOF analysis. Structural elucidation of the O111 substructure by NMR analysis further demonstrated replacement of the hydroxyl group with an N-acetyl group on the terminal glucose residue of the O-antigen pentasaccharide repeating unit. To our knowledge, this study is the first to provide a detailed structural analysis of a new O-antigen substructure from the E. coli O111 serogroup.
大肠杆菌 O111 血清型是一种重要的致病性大肠杆菌菌株,可引起严重的、潜在的致命并发症。尽管有报道称大肠杆菌 O111 的 O 抗原多糖存在变异,但目前仅有一种结构被报道。本文利用基质辅助激光解吸电离飞行时间(MALDI-TOF)质谱法和核磁共振分析鉴定了大肠杆菌 O111 的 O 抗原子结构。MALDI 糖型分析表明,O111 血清群的大肠杆菌菌株和脂多糖的 O 抗原重复单位质量分别为 Δm/z 787 和 828。LIFT-TOF/TOF分析进一步证实了这一点。通过核磁共振分析对 O111 亚结构的阐明进一步表明,O 抗原五糖重复单元末端葡萄糖残基上的羟基被 N-乙酰基取代。据我们所知,这项研究首次对大肠杆菌 O111 血清群的一种新的 O 型抗原亚结构进行了详细的结构分析。
{"title":"Integration of MALDI glycotyping and NMR analysis to uncover an O-antigen substructure from pathogenic Escherichia coli O111.","authors":"June Chelyn Lee, Shogo Urakami, Hiroshi Hinou","doi":"10.1016/j.ijbiomac.2024.137178","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2024.137178","url":null,"abstract":"<p><p>Escherichia coli O111 serotype is a critical pathogenic E. coli strain that causes severe, potentially fatal complications. Despite its reported variation, only one structure of the O-antigen polysaccharide from E. coli O111 has been reported. Here, a substructure of the O-antigen from E. coli O111 was characterized using matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry and NMR analysis. MALDI glycotyping revealed differing O-antigen repeating unit masses of Δm/z 787 and 828 in the E. coli strains and lipopolysaccharides from the O111 serogroup. This variation was caused by the replacement of the hexose residue with hexosamine in the repeating units, which was further confirmed by LIFT-TOF/TOF analysis. Structural elucidation of the O111 substructure by NMR analysis further demonstrated replacement of the hydroxyl group with an N-acetyl group on the terminal glucose residue of the O-antigen pentasaccharide repeating unit. To our knowledge, this study is the first to provide a detailed structural analysis of a new O-antigen substructure from the E. coli O111 serogroup.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589484","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}
Pub Date : 2024-11-04DOI: 10.1016/j.ijbiomac.2024.137148
Ettore Napolitano, Andrea Criscuolo, Claudia Riccardi, Chiara Platella, Rosa Gaglione, Angela Arciello, Domenica Musumeci, Daniela Montesarchio
In this work, we present the case of the G-quadruplex(G4)-forming aptamers we recently identified for the recognition of HMGB1, protein involved in inflammatory, autoimmune diseases and cancer. These aptamers were previously analyzed, without annealing them, after proper dilution of the stock solution in a pseudo-physiological buffer mimicking the extracellular environment where the protein exerts its pathological activity, and showed high thermal stability and nuclease resistance, good protein affinity and remarkable in vitro activity. These features were more marked for the aptamers forming dimeric, parallel G4 structures in solution. Herein, we fully characterized the same anti-HMGB1 aptamers after a standard annealing procedure performed on diluted samples. Notably, upon a thermal unfolding/folding cycle, these aptamers, and particularly the best ones in the not-annealed form, showed significant conformational switches compared to the same systems analyzed without annealing, forming exclusively monomeric G4 structures, featured by poor thermal and enzymatic stabilities, along with lower protein affinities. These results prove that, for these aptamers, analyzed in the chosen conditions, annealing at low concentration does not produce a beneficial effect in terms of favouring the most bioactive species.
{"title":"When annealing is detrimental: The case of HMGB1-targeting G-quadruplex aptamers.","authors":"Ettore Napolitano, Andrea Criscuolo, Claudia Riccardi, Chiara Platella, Rosa Gaglione, Angela Arciello, Domenica Musumeci, Daniela Montesarchio","doi":"10.1016/j.ijbiomac.2024.137148","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2024.137148","url":null,"abstract":"<p><p>In this work, we present the case of the G-quadruplex(G4)-forming aptamers we recently identified for the recognition of HMGB1, protein involved in inflammatory, autoimmune diseases and cancer. These aptamers were previously analyzed, without annealing them, after proper dilution of the stock solution in a pseudo-physiological buffer mimicking the extracellular environment where the protein exerts its pathological activity, and showed high thermal stability and nuclease resistance, good protein affinity and remarkable in vitro activity. These features were more marked for the aptamers forming dimeric, parallel G4 structures in solution. Herein, we fully characterized the same anti-HMGB1 aptamers after a standard annealing procedure performed on diluted samples. Notably, upon a thermal unfolding/folding cycle, these aptamers, and particularly the best ones in the not-annealed form, showed significant conformational switches compared to the same systems analyzed without annealing, forming exclusively monomeric G4 structures, featured by poor thermal and enzymatic stabilities, along with lower protein affinities. These results prove that, for these aptamers, analyzed in the chosen conditions, annealing at low concentration does not produce a beneficial effect in terms of favouring the most bioactive species.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589565","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}
Pub Date : 2024-11-04DOI: 10.1016/j.ijbiomac.2024.136990
Dipranil Dutta, Sankar Pajaniradje, Anjali Suresh Nair, Sathyapriya Chandramohan, Suhail Ahmad Bhat, E Manikandan, Rukkumani Rajagopalan
Natural compounds like Curcumin with anti-cancer, anti-inflammatory and anti-bacterial properties are good target for drug development but its poor aqueous solubility, bioavailability, and low retention properties makes it a poor drug candidate in clinical settings. Here in this study, we have used an indole curcumin analogue (ICA) that has better bioavailability and enhanced permeability and retention (EPR) effect than curcumin. To make an active targeting drug we have designed folic acid conjugated chitosan-based nanoparticles encapsulating Indole curcumin analogue (CS-FA-ICA-np). The physical characteristics of CS-FA-ICA-np were evaluated by DLS, SEM, FTIR, XPS, XRD and TGA. Anti-cancer activity was analyzed using MTT, Fluorescence staining, Flow cytometry, comet assay, DNA fragmentation assay, wound healing, gelatin zymography, chick chorioallantoic membrane (CAM) assay and hemolysis assay. The size of CS-FA-ICA-nps were found to be 111 nm, and spherical in shape as observed in SEM. In-vitro assays show that CS-FA-ICA np has IC50 of 90 μg/mL in MDA-MB-231, increases ROS concentration, arrests cell cycle in G2-M phase, reduces matrix metalloproteinase-9 (MMP-9) activity and initiates apoptosis in cancer cells. Our results indicate that encapsulation of ICA increases its anti-cancer effect, drug stability, enhanced drug delivery to cancer microenvironment.
{"title":"An in-vitro study of active targeting & anti-cancer effect of folic acid conjugated chitosan encapsulated indole curcumin analogue nanoparticles.","authors":"Dipranil Dutta, Sankar Pajaniradje, Anjali Suresh Nair, Sathyapriya Chandramohan, Suhail Ahmad Bhat, E Manikandan, Rukkumani Rajagopalan","doi":"10.1016/j.ijbiomac.2024.136990","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2024.136990","url":null,"abstract":"<p><p>Natural compounds like Curcumin with anti-cancer, anti-inflammatory and anti-bacterial properties are good target for drug development but its poor aqueous solubility, bioavailability, and low retention properties makes it a poor drug candidate in clinical settings. Here in this study, we have used an indole curcumin analogue (ICA) that has better bioavailability and enhanced permeability and retention (EPR) effect than curcumin. To make an active targeting drug we have designed folic acid conjugated chitosan-based nanoparticles encapsulating Indole curcumin analogue (CS-FA-ICA-np). The physical characteristics of CS-FA-ICA-np were evaluated by DLS, SEM, FTIR, XPS, XRD and TGA. Anti-cancer activity was analyzed using MTT, Fluorescence staining, Flow cytometry, comet assay, DNA fragmentation assay, wound healing, gelatin zymography, chick chorioallantoic membrane (CAM) assay and hemolysis assay. The size of CS-FA-ICA-nps were found to be 111 nm, and spherical in shape as observed in SEM. In-vitro assays show that CS-FA-ICA np has IC<sub>50</sub> of 90 μg/mL in MDA-MB-231, increases ROS concentration, arrests cell cycle in G2-M phase, reduces matrix metalloproteinase-9 (MMP-9) activity and initiates apoptosis in cancer cells. Our results indicate that encapsulation of ICA increases its anti-cancer effect, drug stability, enhanced drug delivery to cancer microenvironment.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589374","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}
Pub Date : 2024-11-04DOI: 10.1016/j.ijbiomac.2024.137262
Mohamed A Mohamady Hussein, Eman S Alamri, Hala M Bayomy, Aishah N Albalawi, Mariusz Grinholc, Mamoun Muhammed
This study presents fabrication and characterization of novel chamomile essential oil (CMO)/gallic acid-stabilized silver nanoparticles (gallic acid-nanosilver, GNS), embedded into polylactic acid (PLA)-based hybrid bilayer nanofibers (NFs). Where CMO was impregnated into polyvinyl alcohol (PVA)-polyethylene glycol (PEG) solution and electrospun simultaneously with PLA to obtain PLA/PVA-PEG-CMO NFs (PLA/CMO A2). Meanwhile, GNS were added to PVA-PEG-CMO and electrospun to obtain PLA/PVA-PEG-CMO-GNS NFs (PLA/CMO-GNS A3). Where pure PLA/PVA-PEG NFs were coded pure PLA/A1. Physicochemical properties of fabricated bilayer-NFs were performed using various approaches. Besides, porosity%, swelling, biodegradability, CMO release pattern, antioxidant, antibacterial activity and cytotoxicity were investigated. Study investigation revealed PLA-based bilayer NFs exhibited a biphasic release profile for impregnated CMO. Due to presence of GA, antioxidant property and biocompatibility of PLA/CMO-GNS A3 was superior compared to pure PLA/A1 and PLA/CMO A2. Antibacterial activity was enhanced in presence of CMO in PLA/CMO A2 than pure PLA/A1. Furthermore, addition of GNS in PLA/CMO-GNS A3 displayed highest antibacterial activity due to synergy of CMO/GNS. Finally, MTT assay with HFB4 fibroblasts demonstrated absence of cytotoxicity of bilayer-based NFs. Thus, study suggests that developed PLA/PVA-PEG NFs could be a promising candidate for tissue regeneration and food edible packaging in particular when impregnated with both CMO/GNS.
{"title":"Developing novel hybrid bilayer nanofibers based on polylactic acid with impregnation of chamomile essential oil and gallic acid-stabilized silver nanoparticles.","authors":"Mohamed A Mohamady Hussein, Eman S Alamri, Hala M Bayomy, Aishah N Albalawi, Mariusz Grinholc, Mamoun Muhammed","doi":"10.1016/j.ijbiomac.2024.137262","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2024.137262","url":null,"abstract":"<p><p>This study presents fabrication and characterization of novel chamomile essential oil (CMO)/gallic acid-stabilized silver nanoparticles (gallic acid-nanosilver, GNS), embedded into polylactic acid (PLA)-based hybrid bilayer nanofibers (NFs). Where CMO was impregnated into polyvinyl alcohol (PVA)-polyethylene glycol (PEG) solution and electrospun simultaneously with PLA to obtain PLA/PVA-PEG-CMO NFs (PLA/CMO A2). Meanwhile, GNS were added to PVA-PEG-CMO and electrospun to obtain PLA/PVA-PEG-CMO-GNS NFs (PLA/CMO-GNS A3). Where pure PLA/PVA-PEG NFs were coded pure PLA/A1. Physicochemical properties of fabricated bilayer-NFs were performed using various approaches. Besides, porosity%, swelling, biodegradability, CMO release pattern, antioxidant, antibacterial activity and cytotoxicity were investigated. Study investigation revealed PLA-based bilayer NFs exhibited a biphasic release profile for impregnated CMO. Due to presence of GA, antioxidant property and biocompatibility of PLA/CMO-GNS A3 was superior compared to pure PLA/A1 and PLA/CMO A2. Antibacterial activity was enhanced in presence of CMO in PLA/CMO A2 than pure PLA/A1. Furthermore, addition of GNS in PLA/CMO-GNS A3 displayed highest antibacterial activity due to synergy of CMO/GNS. Finally, MTT assay with HFB4 fibroblasts demonstrated absence of cytotoxicity of bilayer-based NFs. Thus, study suggests that developed PLA/PVA-PEG NFs could be a promising candidate for tissue regeneration and food edible packaging in particular when impregnated with both CMO/GNS.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589462","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}
Pub Date : 2024-11-04DOI: 10.1016/j.ijbiomac.2024.137242
Pei-Hsuan Chung, Feng-Huei Lin, I-Hsuan Liu
Osteoarthritis burdens patients due to the limited regenerative capacity of chondrocytes. Traditional cartilage repair often falls short, necessitating innovative approaches. Mesenchymal stem cells (MSCs) show promise for regeneration. Heparan sulfate glycosaminoglycans (HS-GAGs) regulate cellular functions, making them a target for cartilage repair. This study highlights how Heparinase III (HepIII) cleaves intact HS-GAGs in bone marrow-derived MSCs (BM-MSCs), enhancing their capabilities and specifically promoting chondrogenesis. HepIII-treated BM-MSCs cultured in a hanging drop device for three days, significantly increased cell number and aggregation into a cell sphere with early chondrogenesis. HepIII promoted BM-MSCs toward chondrogenesis, increasing type II collagen, intact HS-GAGs, and sulfated GAG content, while upregulating chondrogenic and heparan sulfate proteoglycan genes. Treatment with the TGF-β inhibitor (SB-431542) in HepIII-treated BM-MSCs demonstrated enhanced intrinsic transforming growth factor-β (TGF-β) signaling and fibronectin expression. This approach also boosted BM-MSC self-renewal, immunosuppressive potential, and modified acetylated histone signatures, offering a cost-effective strategy for cartilage repair by addressing inflammation, metabolic changes, and the high costs of traditional TGF-β methods. From the results, HepIII-treated BM-MSCs show potential for use in combination with other biopolymers as injectable gels to improve cartilage repair in osteoarthritis patients in the near future.
{"title":"Enhancing intrinsic TGF-β signaling via heparan sulfate glycosaminoglycan regulation to promote mesenchymal stem cell capabilities and chondrogenesis for cartilage repair.","authors":"Pei-Hsuan Chung, Feng-Huei Lin, I-Hsuan Liu","doi":"10.1016/j.ijbiomac.2024.137242","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2024.137242","url":null,"abstract":"<p><p>Osteoarthritis burdens patients due to the limited regenerative capacity of chondrocytes. Traditional cartilage repair often falls short, necessitating innovative approaches. Mesenchymal stem cells (MSCs) show promise for regeneration. Heparan sulfate glycosaminoglycans (HS-GAGs) regulate cellular functions, making them a target for cartilage repair. This study highlights how Heparinase III (HepIII) cleaves intact HS-GAGs in bone marrow-derived MSCs (BM-MSCs), enhancing their capabilities and specifically promoting chondrogenesis. HepIII-treated BM-MSCs cultured in a hanging drop device for three days, significantly increased cell number and aggregation into a cell sphere with early chondrogenesis. HepIII promoted BM-MSCs toward chondrogenesis, increasing type II collagen, intact HS-GAGs, and sulfated GAG content, while upregulating chondrogenic and heparan sulfate proteoglycan genes. Treatment with the TGF-β inhibitor (SB-431542) in HepIII-treated BM-MSCs demonstrated enhanced intrinsic transforming growth factor-β (TGF-β) signaling and fibronectin expression. This approach also boosted BM-MSC self-renewal, immunosuppressive potential, and modified acetylated histone signatures, offering a cost-effective strategy for cartilage repair by addressing inflammation, metabolic changes, and the high costs of traditional TGF-β methods. From the results, HepIII-treated BM-MSCs show potential for use in combination with other biopolymers as injectable gels to improve cartilage repair in osteoarthritis patients in the near future.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589471","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}
Pub Date : 2024-11-03DOI: 10.1016/j.ijbiomac.2024.137193
Shangsi Chen, Jiahui Lai, Jizhuo Chen, Liwu Zheng, Min Wang
Surgical resection is an efficient treatment for cancerous tissues and uterine fibroids in the women uterus. However, the insufficiency of clinical interventions could result in tumor recurrence, and the defective tissues remained would cause intrauterine adhesions (IUAs) and further affect reproduction capacity. In this study, 3D printed hydrogel/poly(l-lactide-co-trimethylene carbonate) (PLLA-co-TMC, "PTMC" in short) core/shell scaffolds with NIR-tuned doxorubicin hydrochloride (DOX) and estradiol (E2) dual release were designed and fabricated for cancer therapy and uterine regeneration. Gelatin (Gel) and DOX were homogeneously mixed and then 3D printed to form Gel-DOX scaffolds. Gel-DOX scaffolds were then immersed in PTMC-PDA@E2 solution to fabricate Gel-DOX/PTMC-PDA@E2 core/shell scaffolds. Consequently, Gel-DOX/PTMC-PDA@E2 scaffolds could release DOX and E2 in a chronological manner, firstly delivering DOX assisted by phototherapy (PTT) to effectively kill Hela cells and then sustainably releasing E2 to promote uterine tissue regeneration. In vitro experiments showed that core/shell scaffolds exhibited excellent anticancer efficiency through the synergy of DOX release and hyperthermia ablation. Moreover, E2 could be sustainably released for over 28 days in vitro to promote the proliferation of bone marrow-derived mesenchymal stem cells (BMSCs). The novel Gel-DOX/PTMC-PDA@E2 core/shell scaffolds have therefore exhibited potential promise for the treatment of cancer therapy and uterine regeneration.
手术切除是治疗妇女子宫癌组织和子宫肌瘤的有效方法。然而,临床干预不足会导致肿瘤复发,残留的缺陷组织会造成宫腔内粘连(IUAs),进一步影响生育能力。本研究设计并制作了具有近红外调谐盐酸多柔比星(DOX)和雌二醇(E2)双释放功能的三维打印水凝胶/聚(l-乳酸-碳酸三亚甲基酯)(PLLA-co-TMC,简称 "PTMC")核/壳支架,用于癌症治疗和子宫再生。将明胶(Gel)和 DOX 均匀混合,然后通过 3D 打印形成 Gel-DOX 支架。然后将凝胶-DOX支架浸入PTMC-PDA@E2溶液中,制成Gel-DOX/PTMC-PDA@E2核/壳支架。因此,Gel-DOX/PTMC-PDA@E2支架可按时间顺序释放DOX和E2,首先在光疗(PTT)辅助下释放DOX,有效杀死Hela细胞,然后持续释放E2,促进子宫组织再生。体外实验表明,通过释放 DOX 和热疗消融的协同作用,核/壳支架表现出卓越的抗癌效率。此外,E2可在体外持续释放28天以上,以促进骨髓间充质干细胞(BMSCs)的增殖。因此,新型凝胶-DOX/PTMC-PDA@E2核/壳支架在癌症治疗和子宫再生方面具有潜在的应用前景。
{"title":"3D printed gelatin/PTMC core/shell scaffolds with NIR laser-tuned drug/biomolecule release for cancer therapy and uterine regeneration.","authors":"Shangsi Chen, Jiahui Lai, Jizhuo Chen, Liwu Zheng, Min Wang","doi":"10.1016/j.ijbiomac.2024.137193","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2024.137193","url":null,"abstract":"<p><p>Surgical resection is an efficient treatment for cancerous tissues and uterine fibroids in the women uterus. However, the insufficiency of clinical interventions could result in tumor recurrence, and the defective tissues remained would cause intrauterine adhesions (IUAs) and further affect reproduction capacity. In this study, 3D printed hydrogel/poly(l-lactide-co-trimethylene carbonate) (PLLA-co-TMC, \"PTMC\" in short) core/shell scaffolds with NIR-tuned doxorubicin hydrochloride (DOX) and estradiol (E2) dual release were designed and fabricated for cancer therapy and uterine regeneration. Gelatin (Gel) and DOX were homogeneously mixed and then 3D printed to form Gel-DOX scaffolds. Gel-DOX scaffolds were then immersed in PTMC-PDA@E2 solution to fabricate Gel-DOX/PTMC-PDA@E2 core/shell scaffolds. Consequently, Gel-DOX/PTMC-PDA@E2 scaffolds could release DOX and E2 in a chronological manner, firstly delivering DOX assisted by phototherapy (PTT) to effectively kill Hela cells and then sustainably releasing E2 to promote uterine tissue regeneration. In vitro experiments showed that core/shell scaffolds exhibited excellent anticancer efficiency through the synergy of DOX release and hyperthermia ablation. Moreover, E2 could be sustainably released for over 28 days in vitro to promote the proliferation of bone marrow-derived mesenchymal stem cells (BMSCs). The novel Gel-DOX/PTMC-PDA@E2 core/shell scaffolds have therefore exhibited potential promise for the treatment of cancer therapy and uterine regeneration.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581007","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}
Pub Date : 2024-11-03DOI: 10.1016/j.ijbiomac.2024.137255
Nafise Kazemi, S A Hassanzadeh-Tabrizi, Narjes Koupaei, Hamed Ghomi, Elahe Masaeli
Tissue engineering has emerged as a promising substitute for traditional tissue repair methods. Nowadays, advancements in 3D printing technology have enabled the fabrication of customized scaffolds to support tissue regeneration. In the present study, a polylactic acid-polyvinylpyrrolidone 3D-printed scaffold containing 10 % forsterite was fabricated. Subsequently, lyophilized fucoidan microstructures loaded with sildenafil were filled the channels of this 3D-printed scaffold. The fabricated scaffold loaded with sildenafil was thoroughly characterized, revealing that 97.46 % of the loaded sildenafil was released in a sustained manner over 28 days. Furthermore, the biocompatibility of MG63 was evaluated through cell viability and adhesion tests. The findings indicated a direct and favorable influence on cell behavior. Based on the chicken chorioallantoic membrane assay, the fabricated scaffold significantly increases angiogenesis due to the sustained release of sildenafil. Moreover, in-vivo studies conducted on a rat model demonstrated that the 3D-printed scaffold was able to stimulate and accelerate the repair of calvarial defects within 8 weeks, and the amount of new bone tissue formation was significantly higher than that of other experimental groups. Based on the comprehensive in-vitro and in-vivo assessments, the scaffold with a macro- and microporous structure combined with the ability to release sildenafil is suggested as a potential candidate for repairing bone tissue, especially in the context of skull defects.
{"title":"Highly porous sildenafil loaded polylactic acid/polyvinylpyrrolidone based 3D printed scaffold containing forsterite nanoparticles for craniofacial reconstruction.","authors":"Nafise Kazemi, S A Hassanzadeh-Tabrizi, Narjes Koupaei, Hamed Ghomi, Elahe Masaeli","doi":"10.1016/j.ijbiomac.2024.137255","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2024.137255","url":null,"abstract":"<p><p>Tissue engineering has emerged as a promising substitute for traditional tissue repair methods. Nowadays, advancements in 3D printing technology have enabled the fabrication of customized scaffolds to support tissue regeneration. In the present study, a polylactic acid-polyvinylpyrrolidone 3D-printed scaffold containing 10 % forsterite was fabricated. Subsequently, lyophilized fucoidan microstructures loaded with sildenafil were filled the channels of this 3D-printed scaffold. The fabricated scaffold loaded with sildenafil was thoroughly characterized, revealing that 97.46 % of the loaded sildenafil was released in a sustained manner over 28 days. Furthermore, the biocompatibility of MG63 was evaluated through cell viability and adhesion tests. The findings indicated a direct and favorable influence on cell behavior. Based on the chicken chorioallantoic membrane assay, the fabricated scaffold significantly increases angiogenesis due to the sustained release of sildenafil. Moreover, in-vivo studies conducted on a rat model demonstrated that the 3D-printed scaffold was able to stimulate and accelerate the repair of calvarial defects within 8 weeks, and the amount of new bone tissue formation was significantly higher than that of other experimental groups. Based on the comprehensive in-vitro and in-vivo assessments, the scaffold with a macro- and microporous structure combined with the ability to release sildenafil is suggested as a potential candidate for repairing bone tissue, especially in the context of skull defects.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581336","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}
Pub Date : 2024-11-03DOI: 10.1016/j.ijbiomac.2024.137206
Currently, numerous bone tumor patients undergo tumor recurrence after surgical resection, which seriously affects their quality of life. In this study, the ceria (CeO2) nanoparticle was added to Poly-L-Lactic Acid (PLLA) bone implants endowing the bone implant with antitumor function. The results showed that the reactive oxygen species increased in U2OS cells while it dropped in HEK293 cells as the CeO2 content increased. Meanwhile, the PLLA-8CeO2 showed a high cell inhibition rate of 53.66 % for U2OS cells and possessed a high cell viability of 76.96 ± 2.20 % for HEK293 cells, meaning that the implant could kill bone tumor cells meanwhile show good cytocompatibility for normal cells. These were mainly due to the fact that the CeO2 nanoparticles acted as a superoxide dismutase in tumor cells reducing superoxide to hydrogen peroxide, inducing an increase in reactive oxygen species levels. The excess reactive oxygen species could result in tumor cell apoptosis by disrupting mitochondrial structure, oxidizing proteins, and promoting DNA denaturation. Moreover, the compressive strength of PLLA was improved by the CeO2 addition due to its particle dispersion strengthening. Besides, the PLLA-CeO2 had a faster degradation rate compared to PLLA. Overall, the PLLA-CeO2 is a promising implant material for bone tumor treatment.
{"title":"Utilizing the superoxide dismutase activity of ceria nanoparticles to endow poly-l-lactic acid bone implants with antitumor function","authors":"","doi":"10.1016/j.ijbiomac.2024.137206","DOIUrl":"10.1016/j.ijbiomac.2024.137206","url":null,"abstract":"<div><div>Currently, numerous bone tumor patients undergo tumor recurrence after surgical resection, which seriously affects their quality of life. In this study, the ceria (CeO<sub>2</sub>) nanoparticle was added to Poly-L-Lactic Acid (PLLA) bone implants endowing the bone implant with antitumor function. The results showed that the reactive oxygen species increased in U2OS cells while it dropped in HEK293 cells as the CeO<sub>2</sub> content increased. Meanwhile, the PLLA-8CeO<sub>2</sub> showed a high cell inhibition rate of 53.66 % for U2OS cells and possessed a high cell viability of 76.96 ± 2.20 % for HEK293 cells, meaning that the implant could kill bone tumor cells meanwhile show good cytocompatibility for normal cells. These were mainly due to the fact that the CeO<sub>2</sub> nanoparticles acted as a superoxide dismutase in tumor cells reducing superoxide to hydrogen peroxide, inducing an increase in reactive oxygen species levels. The excess reactive oxygen species could result in tumor cell apoptosis by disrupting mitochondrial structure, oxidizing proteins, and promoting DNA denaturation. Moreover, the compressive strength of PLLA was improved by the CeO<sub>2</sub> addition due to its particle dispersion strengthening. Besides, the PLLA-CeO<sub>2</sub> had a faster degradation rate compared to PLLA. Overall, the PLLA-CeO<sub>2</sub> is a promising implant material for bone tumor treatment.</div></div>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581350","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}