Eri Maai , Mikiko Kojima , Yumiko Takebayashi , Hitoshi Sakakibara
{"title":"Chloroplast arrangement in finger millet under low-temperature conditions","authors":"Eri Maai , Mikiko Kojima , Yumiko Takebayashi , Hitoshi Sakakibara","doi":"10.1016/j.bbagen.2025.130757","DOIUrl":"10.1016/j.bbagen.2025.130757","url":null,"abstract":"<div><h3>Background</h3><div>Finger millet, a C<sub>4</sub> plant with mesophyll and bundle sheath cells, has been cultivated at high altitudes in the Himalayas owing to its adaptability to stressful environments. Under environmental stresses such as high light and drought, finger millet mesophyll chloroplasts move toward the bundle sheath, a phenomenon known as aggregative arrangement.</div></div><div><h3>Methods</h3><div>To investigate the effect of low temperatures on mesophyll chloroplast arrangement in finger millet, we conducted microscopic observations and photochemical measurements using leaves treated at different temperatures in light or darkness, with or without pharmacological inhibitors. Abscisic acid (ABA) content was also quantified.</div></div><div><h3>Results</h3><div>Chloroplast aggregative arrangement was induced at 5 °C in a light- and actin-dependent manner. This response required a lower intensity of blue light than that previously observed at moderate temperatures. Low temperature significantly reduced the maximum quantum efficiency of photosystem II and increased leaf ABA content in the light. Conversely, in the absence of blue light at low temperatures or under actin-inhibited conditions, mesophyll chloroplasts exhibited a doughnut-like arrangement, characterized by a distribution away from the bundle sheath side.</div></div><div><h3>Conclusions</h3><div>In finger millet, mesophyll chloroplasts move toward the bundle sheath through a blue light and actin-based mechanism at low temperatures. The doughnut-like arrangement appears to be a contingent phenomenon that manifests when the dispersion of mesophyll chloroplasts toward the bundle sheath is impeded.</div></div><div><h3>General significance</h3><div>The aggregative arrangement is a response to various environmental stresses, including low temperatures, and may be advantageous for finger millet seedlings in mitigating photoinhibition during cool mornings.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 3","pages":"Article 130757"},"PeriodicalIF":2.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142943626","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}
{"title":"Applications of MicroED in structural biology and structure-based drug discovery","authors":"Salma Mirza , Malik Shoaib Ahmad","doi":"10.1016/j.bbagen.2025.130758","DOIUrl":"10.1016/j.bbagen.2025.130758","url":null,"abstract":"<div><div>Microcrystal electron diffraction (MicroED) is an emerging method for the structure determination of proteins and peptides, enzyme-inhibitor complexes. Several structures of biomolecules, including lysozyme, proteinase K, adenosine receptor A2A, insulin, xylanase, thermolysin, DNA, and Granulovirus occlusion bodies, have been successfully determined through MicroED. As MicroED uses very small crystals for structure determination, therefore, it has several advantages over conventional X-ray diffraction methods. In this review article, we discussed the most recent developments in the field of MicroED and its applications for the structural determination of different types of peptides, proteins, enzymes, DNA, and enzyme-inhibitor-complexed structures.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 3","pages":"Article 130758"},"PeriodicalIF":2.8,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142943628","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}
Yo Yamaguchi , Jun Nagata , Takuma Kawasaki , Takashi Todo , Naoshi Hiramatsu
{"title":"Androgens induce renal synthesis of urinary lipocalin-family protein, a potential inter-sexual transmitter in viviparous rockfish","authors":"Yo Yamaguchi , Jun Nagata , Takuma Kawasaki , Takashi Todo , Naoshi Hiramatsu","doi":"10.1016/j.bbagen.2025.130756","DOIUrl":"10.1016/j.bbagen.2025.130756","url":null,"abstract":"<div><div>In viviparous black rockfish (<em>Sebastes schlegelii</em>), the kidney of reproductive-phase males actively produces lipocalin-type prostaglandin D<sub>2</sub> synthase homolog (LPGDSh) protein, which is presumably involved in inter-sexual communication when emitted in the urine. The present study was undertaken to discover whether androgens and their nuclear receptors (Ars) are engaged in regulation of renal LPGDSh protein synthesis in black rockfish. Quantitative real-time polymerase chain reaction, in conjunction with immunohistochemistry and highly sensitive enzyme-linked immunosorbent assay, revealed that intra-abdominal administration of a synthetic androgen, 17α-methyltestosterone (MT), to juvenile black rockfish induced their renal expression of LPGDSh transcript and protein. In situ hybridization visualized <em>arα</em> and <em>arβ</em> transcripts in the renal tubules of mature males during the copulation season, where they were co-localized with LPGDSh protein. Androgens, such as 11β-hydroxytestosterone, MT, dihydrotestosterone, 11-ketotestosterone (11KT), testosterone, and androstenedione transactivated a luciferase reporter vector containing four repeats of a consensus androgen response element (ARE) in the presence of black rockfish Ars (either Arα or Arβ), with differences in ligand-preference and dose-response profiles being observed between the two Ars. In the presence of 11KT, the Ars transactivated a reporter vector containing the proximal 5′-flanking region of an LPGDSh gene in luciferase reporter assays. The region between 2100 bp and 1110 bp upstream from the start codon of the LPGDSh gene, wherein many ARE-like motifs are densely distributed, was imperative for the androgenic transactivation response of the 5′-flanking region. Collectively, these observations verify that renal synthesis of LPGDSh protein is upregulated by androgens.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 3","pages":"Article 130756"},"PeriodicalIF":2.8,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142963665","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}
Xiao-Lin Sun , Huan-Xi Song , Jia-Hui Li, Yi-Jin Liu, Xin-Ya Wang, Li-Na Zhang
{"title":"TOE1 deadenylase inhibits gastric cancer cell proliferation by regulating cell cycle progression","authors":"Xiao-Lin Sun , Huan-Xi Song , Jia-Hui Li, Yi-Jin Liu, Xin-Ya Wang, Li-Na Zhang","doi":"10.1016/j.bbagen.2024.130736","DOIUrl":"10.1016/j.bbagen.2024.130736","url":null,"abstract":"<div><div>TOE1, also known as hCaf1z, belongs to the DEDD superfamily of deadenylases and a newly identified isoenzyme of hCaf1 deadenylases. Previous research has demonstrated that TOE1 has deadenylase activity, which can catalyze the degradation of poly(A) substrates and interact with hCcr4d to form the unconventional human Ccr4-Caf1 deadenylase complex. Our recent research indicates that hCaf1a and hCaf1b isoenzymes, highly expressed in gastric cancer, promote gastric cancer cell proliferation and tumorigenicity <em>via</em> modulating cell cycle progression. However, no studies have yet explored the relationship between TOE1 deadenylase and tumor development. In our study, we systematically investigated the functions and mechanisms of TOE1 in gastric cancer progression. Our findings revealed that overexpression of TOE1 inhibited gastric cancer cell proliferation, invasion and migration, promoted cell apoptosis, and led to cell cycle arrest in G0/G1 phase, while TOE1 knockdown had the opposite biological effects on these processes in gastric cancer cells. Further results indicated that TOE1 suppressed gastric cancer progression by inhibiting EMT process and MMPs expression. Moreover, our study clarified that TOE1 blocked gastric cancer cell cycle progression by up-regulating the expression level of the key cell cycle factors p21 and p53 through different regulatory mechanisms. Specifically, TOE1 up-regulated p53 expression by enhancing p53 promoter activity, and up-regulated p21 expression by enhancing <em>p21</em> mRNA stability. Collectively, our findings first contribute to further elucidating the molecular mechanisms by which TOE1 participates in the regulation of gastric cancer progression, and are expected to provide a theoretical basis for diagnosis and targeted treatment of gastric cancer.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 1","pages":"Article 130736"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805925","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}
Jessica E. Rodríguez , Erik Andrade-Jorge , Alina Barquet-Nieto , Samuel E. Estrada-Soto , Itzell A. Gallardo-Ortíz , Rafael Villalobos-Molina
{"title":"BMY 7378, a selective α1D-adrenoceptor antagonist, is a new angiotensin converting enzyme inhibitor: In silico, in vitro and in vivo approach","authors":"Jessica E. Rodríguez , Erik Andrade-Jorge , Alina Barquet-Nieto , Samuel E. Estrada-Soto , Itzell A. Gallardo-Ortíz , Rafael Villalobos-Molina","doi":"10.1016/j.bbagen.2024.130732","DOIUrl":"10.1016/j.bbagen.2024.130732","url":null,"abstract":"<div><div>BMY 7378 is a multitarget drug primarily known for its selective antagonism of α<sub>1D</sub>-adrenoceptors (α<sub>1D</sub>-AR), exhibiting both hypotensive effects and the ability to prevent or reverse angiotensin II-induced vascular hypertrophy. Notably, BMY 7378 contains a phenylpiperazine moiety, a structural feature associated with angiotensin-converting enzyme (ACE) inhibition. This study aimed to investigate ACE inhibition as a potential pharmacological mechanism of BMY 7378. Using an <em>in silico</em> approach we predicted BMY 7378 interactions with the ACE active site, followed by <em>in vitro</em> activity assays. Additionally, ACE protein expression in the heart was analyzed following four weeks of BMY 7378 treatment in 7–8-month-old spontaneously hypertensive rats (SHR). All assays were benchmarked against captopril, a standard ACE inhibitor. <em>In silico</em> results showed that BMY 7378 binds to the ACE active site, though with reduced interaction with Zn701 (73.7 % compared to captopril), likely due to the pKa of its amino group. The inhibitory concentration 50 (IC<sub>50</sub>) for BMY 7378 was 136 μM, lower than other reported phenylpiperazine derivatives. Furthermore, BMY 7378 significantly increased ACE expression in the hearts of SHR, with an increase of 8.5-fold compared to captopril. In conclusion, BMY 7378 exhibits dual activity as an α<sub>1D</sub>-AR antagonist and an ACE inhibitor, making it a promising pharmacological tool for investigating and potentially treating hypertension and its associated cardiovascular complications.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 1","pages":"Article 130732"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779463","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}
{"title":"Molecular mechanism of action of tetracycline-loaded calcium phosphate nanoparticle to kill multi-drug resistant bacteria","authors":"Susmita Nandi , Soumajit Chakrabarty , Pathikrit Bandopadhyay , Dipanwita Mandal , Md Azaharuddin , Abhijit Das , Anabadya Pal , Sourav Ghosh , Sanchita Nandy , Upasana Sett , Tarakdas Basu","doi":"10.1016/j.bbagen.2024.130733","DOIUrl":"10.1016/j.bbagen.2024.130733","url":null,"abstract":"<div><h3>Background</h3><div>In earlier communications we reported about nanonization of the antibiotic tetracycline (Tet) by entrapping it within the biocompatible and highly membrane penetrating nano-carrier molecule – calcium phosphate nanoparticle (CPNP). The synthesized Tet-CPNP killed different Tet-resistant bacteria <em>in vitro</em> as well as <em>in vivo</em> (in mice). Moreover, such nanonized tetracycline had bactericidal mode of action, in contrast to bacteriostatic mode of action of bulk tetracycline. The present study unveils the molecular mechanism of action of Tet-CPNP.</div></div><div><h3>Methods</h3><div>This study was conducted to investigate the mode of interaction of Tet-CPNP/Tet with intact 70S bacterial ribosome by the techniques of spectrophotometry, spectrofluorimetry, circular dichroism, gel electrophoresis and transmission electron microscopy.</div></div><div><h3>Results</h3><div>Experimental observations revealed that (i) binding affinity of Tet-CPNP was higher than that of only tetracycline with ribosome and (ii) binding of Tet-CPNP, but not of tetracycline, loosened ribosome conformation, finally disrupting and degrading ribosome.</div></div><div><h3>Conclusion</h3><div>Bactericidal action of Tet-CPNP was rooted from degradation of cellular ribosomes and thereby blockage of protein translation phenomenon. Therefore, the problem of obsolescence of tetracycline, a cheap, first-generation, broad-spectrum antibiotic, due to generation of huge tetracycline-resistant bacteria, can be removed by the Tet-CPNP.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 1","pages":"Article 130733"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790956","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}
{"title":"Functions of unique middle loop and C-terminal tail in GnT-III activity and secretion","authors":"WanXue Bao , Takahiro Yamasaki , Miyako Nakano , Masamichi Nagae , Yasuhiko Kizuka","doi":"10.1016/j.bbagen.2024.130734","DOIUrl":"10.1016/j.bbagen.2024.130734","url":null,"abstract":"<div><h3>Background</h3><div><em>N</em>-Glycan branching modulates the diversity of protein functions. β1,4-<em>N</em>-acetylglucosaminyltransferase III (GnT-III or MGAT3) produces a unique GlcNAc branch, “bisecting GlcNAc”, in <em>N</em>-glycans, and is involved in Alzheimer's disease and cancer. However, the 3D structure and catalytic mechanism of GnT-III are unclear. According to AlphaFold-based structure prediction, GnT-III likely contains two putative disordered segments, a long middle loop (Loop) and a C-terminal tail (Tail). We hypothesized that these segments play important roles in regulating the activity or intracellular behaviors of GnT-III.</div></div><div><h3>Methods</h3><div>We expressed wild-type GnT-III (GnT-III-WT), GnT-III-Loop- and -Tail-deletion mutants in cells. Their <em>in vitro</em> catalytic activity and glycan biosynthesis in cells were examined using high-performance liquid chromatography, UDP-Glo glycosyltransferase assays, and glycomic analysis. Subcellular localization of WT and GnT-III mutants was investigated by immunostaining, and degradation rate and secretion were also examined.</div></div><div><h3>Results</h3><div>The Loop-deletion mutant had higher <em>in vitro</em> and <em>in cellulo</em> activity than GnT-III-WT, indicating that Loop suppresses catalytic activity. In contrast, the Tail-deletion mutant showed weaker activity, increased ER localization, and faster degradation than GnT-III-WT, indicating that Tail is required for proper folding. In addition, deletion of Loop led to aberrant shedding of GnT-III, indicating that Loop contains the cleavage site or regulates GnT-III shedding.</div></div><div><h3>Conclusions</h3><div>Loop and Tail of GnT-III play important roles in catalytic activity, folding and shedding.</div></div><div><h3>General significance</h3><div>Our results provide further understanding of the catalysis and shedding mechanisms of GnT-III and can help in the development of methods for modifying the levels of bisecting GlcNAc on glycoproteins and in cells.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 1","pages":"Article 130734"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799382","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}
{"title":"Computational profiling and pharmacokinetic modelling of Febuxostat: Evaluating its potential as a therapeutic agent for diabetic wound healing","authors":"S. Nirenjen, J. Narayanan","doi":"10.1016/j.bbagen.2024.130735","DOIUrl":"10.1016/j.bbagen.2024.130735","url":null,"abstract":"<div><h3>Background</h3><div>Diabetic wounds, a significant complication of Type 2 Diabetes Mellitus (T2DM), face delayed healing due to impaired inflammation, angiogenesis, and collagen synthesis. This study explores Febuxostat, a xanthine oxidase inhibitor for its therapeutic potential in wound healing. Combining computational approaches and <em>in-vitro</em> assays, the study evaluates its effects on key wound healing pathways, cell viability, migration.</div></div><div><h3>Methodology</h3><div>The potential of Febuxostat in diabetic wound healing was studied using <em>in-silico</em> tools for Molecular docking and ADMET profiling, alongside Molecular dynamics (MD) simulations. Toxicity was assessed with OSIRIS Explorer, and biological activity was predicted using the PASS tool. <em>In-vitro</em> MTT and scratch assays on L929 cells further validated cytotoxicity and wound healing efficacy.</div></div><div><h3>Results</h3><div>Docking analysis revealed strong binding affinities to key wound healing targets, including VEGF (−9.11 kcal/mol) and NFKβ (−8.62 kcal/mol). Pharmacokinetic studies highlighted favorable skin permeability, supporting topical applications. Toxicity predictions indicated a safe profile. Molecular dynamics simulations demonstrated stable protein-ligand complexes, particularly with VEGF. Cytotoxicity studies on L929 cells revealed an IC<sub>50</sub> of 6.08 μM and the scratch assay demonstrated significant wound healing activity, highlighting its effectiveness in promoting cell migration and closure.</div></div><div><h3>Conclusion</h3><div>Febuxostat shows remarkable potential in enhancing diabetic wound healing by promoting cell migration, targeting wound-healing proteins, as demonstrated through <em>in-silico</em> and <em>in-vitro</em> studies. This drug is poised to effectively treat diabetic wounds, accelerating healing and reducing complications. Rigorous pre-clinical and clinical evaluations are essential to validate its safety, efficacy, and therapeutic potential.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 1","pages":"Article 130735"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799320","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}
{"title":"Editorial: \"New aspects of glycosyltransferase\".","authors":"Yasuhiko Kizuka","doi":"10.1016/j.bbagen.2024.130750","DOIUrl":"https://doi.org/10.1016/j.bbagen.2024.130750","url":null,"abstract":"","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":" ","pages":"130750"},"PeriodicalIF":2.8,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891754","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}
Shan Wang , Xu Chu , Zhaoyang Liu , Congwei Wang , Zhongyu Fan , Yazhou Chen , Zhengguo Zhang
{"title":"Extracellular matrix stiffness facilitates neurite outgrowth by reprogramming the fatty acid oxidation-dependent macrophage polarization","authors":"Shan Wang , Xu Chu , Zhaoyang Liu , Congwei Wang , Zhongyu Fan , Yazhou Chen , Zhengguo Zhang","doi":"10.1016/j.bbagen.2024.130731","DOIUrl":"10.1016/j.bbagen.2024.130731","url":null,"abstract":"<div><div>The extracellular matrix (ECM) is involved in various of pathophysiology processes, such as wound healing and neurogenesis. During tissue injury, the recruited bone marrow-derived monocytes in the impaired site undergo functional and phenotypic changes and participate in the initiation, maintenance, and resolution phases of tissue repair. However, the effects of ECM stiffness on monocyte differentiation and function remain largely unknown. Herein, we developed a gelatin-hydroxyphenylpropionic acid-based hydrogel with different substrate stiffnesses by varying hydrogen peroxide concentrations, which demonstrated good biocompatibility. Furthermore, the high substrate stiffness hydrogel could polarize macrophage into immunosuppressive phenotype with increased expression of interleukin 10, transforming growth factor β, CD206, and CD163. Twenty three differentially expressed metabolites were identified in stiff hydrogel-cultured macrophages in comparison with soft hydrogel cultured macrophages via metabolite analysis. In addition, 4-hydroxybenzoic acid was the most upregulated metabolite, which could confer protection against neuronal and acute inflammation. Mechanistically, the high substrate stiffness induced macrophage immunosuppressive differentiation by upregulating the expression of the fatty acid oxidation (FAO)-related proteins peroxisome proliferator-activated receptor (PPAR)-γ and PPAR-δ. Consistently, the FAO inhibitor etomoxir reversed the high substrate stiffness mediated macrophage immunosuppressive polarization and neurite outgrowth. Therefore, the alteration in macrophage phenotype induced by increased substrate stiffness can promote tissue repair in clinical applications.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 1","pages":"Article 130731"},"PeriodicalIF":2.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142700958","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}