Archives of biochemistry and biophysics最新文献

{"title":"Imaging oligomers of alpha-toxin (Hla) variants using high-speed AFM and neutralizing Hla hemolytic activity with their antisera","authors":"Ngan Thi Phuong Le ,&nbsp;Kien Xuan Ngo ,&nbsp;Trinh Thi Ngoc Nguyen ,&nbsp;Linh-Thuoc Tran ,&nbsp;Hoang Duc Nguyen","doi":"10.1016/j.abb.2025.110403","DOIUrl":"10.1016/j.abb.2025.110403","url":null,"abstract":"<div><div>Alpha-toxin (Hla) variants, such as the toxoids HlaH35A, HlaH35L, and HlaH35LH48L, have been shown to lack hemolytic activity and present promising antigen sources for vaccine development against <em>S. aureus</em>. The His35 site is critical in the oligomerization process of Hla during transmembrane pore formation, leading to cell lysis. This study employed high-speed atomic force microscopy (HS-AFM) to image the structures of HlaH35A, HlaH35L, and HlaH35LH48L proteins on POPC/Chol lipid membranes. Single-site His35 mutations (HlaH35A, HlaH35L) could form oligomer structures, whereas the double-site HlaH35LH48L mutation resulted in the monomer state. These HS-AFM findings confirm that the region between His35 and His48 is crucial for protomer-protomer interactions essential for oligomerization and pore formation. Hemolytic activity of wild-type Hla on red blood cells (RBCs) was significantly reduced when mixed with HlaH35A, HlaH35L, or HlaH35LH48L at weight ratios 1:5 (HlaWT:toxoid) or higher. However, these toxoids exhibited weak neutralization activities at lower mixing ratios with HlaWT. The increased anti-Hla antibodies (IgG) in mice treated with these Hla toxoids have emerged as a potential treatment avenue to neutralize the hemolytic activity of the HlaWT toxin on RBCs. Serum analysis from mice injected with HlaH35A, HlaH35L, and HlaH35LH48L toxoids showed that these sera could neutralize the hemolytic activity of the HlaWT toxin. Thus, these Hla variants are promising candidates for developing supportive treatments for <em>S. aureus</em> infections.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"768 ","pages":"Article 110403"},"PeriodicalIF":3.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724801","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":"Structure and dynamics of Proteus vulgaris tryptophan indole-lyase complexes with l-ethionine and l-alanine","authors":"Robert S. Phillips ,&nbsp;S. Meredith Brown","doi":"10.1016/j.abb.2025.110402","DOIUrl":"10.1016/j.abb.2025.110402","url":null,"abstract":"<div><div>Tryptophan indole-lyase (TIL; [E.C. 4.1.99.1]) is a pyridoxal-5′-phosphate (PLP) dependent enzyme that catalyzes the reversible β-elimination of indole from <span>l</span>-tryptophan. <span>l</span>-Alanine and <span>l</span>-ethionine are TIL competitive inhibitors that form stable quinonoid complexes with <em>λ_max</em> ∼508 nm. We have now determined the X-ray crystal structure of the tetrameric TIL complexes with <span>l</span>-alanine and <span>l</span>-ethionine, with either K⁺ or Na⁺ in the cation binding site. For the K⁺-form, the structures show a mixture of external aldimine and quinonoid complexes, with both open and closed active site conformations. However, the Na⁺-form exhibits noncovalent and external aldimine complexes in only open active site conformations. Stopped-flow kinetics of <span>l</span>-ethionine binding show that the Na⁺-form of TIL reacts much more slowly than the K⁺-form. The <span>l</span>-alanine and <span>l</span>-ethionine complexes of TIL are affected by hydrostatic pressure, suggesting that solvation contributes to the reaction. As pressure increases, the peak at 508 nm decreases, and a new peak at 344 nm appears. These changes are reversible when pressure is released. The 344 nm species could be either a <em>gem</em>-diamine or an enolimine tautomer of the external aldimine. We measured the fluorescence spectrum of the complex under pressure to differentiate these structures. When excited at either 290 or 325 nm, the complex emits at 400 nm, establishing that it is a <em>gem</em>-diamine complex. This peak does not form when the Na⁺-form of TIL complexed with <span>l</span>-ethionine is subjected to high pressure. Pressure jumps for the TIL-K⁺-<span>l</span>-ethionine complex measured at 508 nm result in pressure dependent relaxation rate constants. The relaxations show a large activation volume in the direction of quinonoid intermediate formation, suggesting that it is coupled with a conformational change. These results provide new insights into the dynamics of ligand binding to TIL.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"768 ","pages":"Article 110402"},"PeriodicalIF":3.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724667","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":"HSPB1 suppresses oxLDL-induced vascular smooth muscle cell ferroptosis by inhibiting DPP4","authors":"Yi Li ,&nbsp;Lijun Zhang ,&nbsp;Qi Zhang ,&nbsp;Yuke Zhang ,&nbsp;Shuang Pan ,&nbsp;Huanhuan Zhao ,&nbsp;Lijun Zhang","doi":"10.1016/j.abb.2025.110400","DOIUrl":"10.1016/j.abb.2025.110400","url":null,"abstract":"<div><h3>Background</h3><div>Atherosclerosis is the major pathological basis of cardiovascular diseases. Vascular smooth muscle cell (VSMC) dysfunction and death induced by oxidized low-density lipoprotein (oxLDL) play a key role in atherosclerosis. Ferroptosis is a novel iron-dependent lipid peroxidation regulated cell death, which is implicated in atherosclerosis. However, whether oxLDL induces VSMC ferroptosis and the specific mechanism is unclear.</div></div><div><h3>Methods</h3><div>To determine the effects of oxLDL on VSMC ferroptosis, LDH activity, MDA and Fe²⁺ content, glutathione peroxidase 4 (GPX4) expression and GPX enzyme activity were assayed. The level of lipid peroxidation was detected by C11 BODIPY fluorescence staining. RT-qPCR and Western blot were used to detect the mRNA and protein expressions of heat shock protein B1 (HSPB1), dipeptidyl peptidase 4 (DPP4) and nuclear factor kappa-B (NF-κB). The siRNAs, plasmids and Val-boropro were utilized to explore the roles of HSPB1/NF-κB/DPP4 in oxLDL-induced VSMC ferroptosis.</div></div><div><h3>Results</h3><div>oxLDL increased LDH activity, Fe²⁺ content, lipid peroxidation and MDA content in VSMCs, which were inhibited by ferroptosis inhibitors Lip-1 and DFO. Moreover, oxLDL reduced GPX4 protein expression and GPX enzyme activity, indicating that oxLDL induces VSMC ferroptosis. Notably, HSPB1 inhibited oxLDL-induced VSMC ferroptosis by reducing the accumulation of Fe²⁺ and lipid peroxidation and increasing GPX4 expression and activity. In addition, HSPB1 suppressed oxLDL-induced VSMC ferroptosis by inhibiting DPP4 through NF-κB. Furthermore, Val-boropro could rescue oxLDL-induced ferroptosis in VSMCs with HSPB1 knockdown by inhibiting DPP4.</div></div><div><h3>Conclusions</h3><div>This study reveals for the first time that HSPB1 suppresses oxLDL-induced VSMC ferroptosis by inhibiting DPP4 through NF-κB, providing new strategies for the prevention and treatment of atherosclerosis.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"768 ","pages":"Article 110400"},"PeriodicalIF":3.8,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708267","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":"UCP2 attenuates neural apoptosis and inflammation in spinal cord injury by inducing the acetylation of ANXA1 and activating the PI3K/AKT pathway","authors":"Guolin Zhu,&nbsp;Junjie Li,&nbsp;Jinxin Luo,&nbsp;Yaojian Rao","doi":"10.1016/j.abb.2025.110399","DOIUrl":"10.1016/j.abb.2025.110399","url":null,"abstract":"<div><div>Spinal cord injury (SCI) represents a prevalent form of mechanical trauma, frequently resulting in significant disability and mortality. Uncoupling protein 2 (UCP2) has been recognized for its neuroprotective properties; however, its specific role in SCI remains to be elucidated. This study aims to investigate the neuroprotective effects of UCP2 in the context of SCI and to further explore its downstream mechanisms of action. Through <em>in vitro</em> experiments, we demonstrated that UCP2 overexpression significantly improved cell viability and inhibited apoptosis and inflammatory responses in the lipopolysaccharides (LPS)-induced SCI cell model. Results of animal experiments showed that adeno-associated virus-mediated overexpression of UCP2 contributed to the recovery of SCI-afflicted rats, evidenced by improved Basso, Beattie, and Bresnahan scores, decreased water content in spinal tissues, reduced number of apoptotic cells in spinal cord. Mechanistic investigations revealed that UCP2 directly interacts with annexin A1 (ANXA1), enhancing its protein stability through acetylation at the K58 site. Furthermore, UCP2 was found to activate the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway by upregulating ANXA1 expression. Rescue assays indicated that knockdown of ANXA1 or inactivation of the PI3K/AKT pathway by LY294002 treatment partially neutralized the protective effects of UCP2 overexpression against apoptosis and inflammatory responses in LPS-stimulated BV-2 cells. Taken together, this study concludes that UCP2 ameliorates apoptosis and inflammatory responses in the SCI model by modulating acetylation-mediated protein stabilization of ANXA1 and activating the PI3K/AKT pathway.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"768 ","pages":"Article 110399"},"PeriodicalIF":3.8,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708223","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":"miR-200 family: Gatekeepers of fibrinolytic regulation in lung pathologies during acute lung injury","authors":"T.M. Jeena ,&nbsp;C. Rakshitha ,&nbsp;Fathimath M Muneesa ,&nbsp;Aleena Varughese ,&nbsp;Akarsha ,&nbsp;Rajesh Raju ,&nbsp;Deepak Krishnan ,&nbsp;Kirana Mugaranja ,&nbsp;Yashodhar P. Bhandary","doi":"10.1016/j.abb.2025.110398","DOIUrl":"10.1016/j.abb.2025.110398","url":null,"abstract":"<div><div>Acute lung injury (ALI) is a severe condition characterized by acute inflammation and respiratory distress, often leading to significant morbidity and mortality. The complex pathophysiology of ALI involves alterations in various molecular and cellular processes, including those regulated by the miR-200 family. This study aims to investigate the regulatory function of miR-200 family members on the fibrinolytic system using three different agents: Bleomycin, IL-17A, and TGF-β, in both <em>in vitro</em> (A549 cells) and <em>in vivo</em> (C57BL/6 mice) models.</div><div>The role of miR-200a and miR-200b in modulating the fibrinolytic system was assessed through mRNA and protein expression analyses. The results show that in both <em>in vitro</em> and <em>in vivo</em> models, treatment with miR-200a and miR-200b mimics greatly reduced the abnormalities caused by the three drugs. Treatments were given during the inflammatory phase of ALI at two different time points for the <em>in vivo</em> studies: 3 and 7 days. This was evidenced by increased uPA and uPAR mRNA levels and decreased PAI-1 mRNA and protein expression. The inverse regulatory roles of miR-200 family members, particularly miR-200a and miR-200b, suggest potential therapeutic targets in ALI.</div><div>Furthermore, our study highlights how IL-17A and TGF-β modulate the fibrinolytic system and EMT pathway by influencing the expression of the miR-200 family in ALI. It elucidates the regulatory function of the miR-200 family in restoring the fibrinolytic system and the EMT pathway during lung injury, underscoring the significant therapeutic potential of miR-200 in treating ALI.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"768 ","pages":"Article 110398"},"PeriodicalIF":3.8,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143698146","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":"Biophysical investigation of metal-substituted D-2-hydroxyglutarate dehydrogenase","authors":"Bilkis Mehrin Moni ,&nbsp;Joanna Afokai Quaye ,&nbsp;Giovanni Gadda","doi":"10.1016/j.abb.2025.110397","DOIUrl":"10.1016/j.abb.2025.110397","url":null,"abstract":"<div><div>D-2-Hydroxyglutarate dehydrogenase from <em>Pseudomonas aeruginosa</em> PAO1 (EC: 1.1.99.39; Uniprot ID: <span><span>Q9I6H4</span><svg><path></path></svg></span>) is a metallo-flavoenzyme that utilizes Zn²⁺ and FAD to catalyze the conversion of D-2-hydroxyglutarate to 2-ketoglutarate. The enzyme utilizes Co²⁺, Ni²⁺, Mn²⁺, and Cd²⁺ as alternative metal cofactors. To study how metal substitution impacts flavin properties, the enzyme was purified with different metal ions or treated with EDTA to generate the metallo-apoenzyme (E_FAD-apo). Fluorescence assays revealed distinct metal ion binding sites in the enzyme: concentrations of metal ions up to ∼0.40 mM increased flavin fluorescence at 531 nm, whereas concentrations above ∼0.40 mM quenched flavin fluorescence with a 2–6 nm bathochromic shift. Concomitantly, enzyme-specific activity exhibited a sigmoidal increase, indicating a metal-induced conformational change. CD spectra showed no significant shifts at ∼209 and ∼220 nm but a ≤ 2-fold increase in mean residue ellipticity compared to E_FAD-apo. Metal binding also caused a 2–9 nm bathochromic shift in flavin absorption and emission maxima, indicating stabilization of the excited-state flavin π-electron system. The binding of Zn²⁺, Co²⁺, Mn²⁺, or Cd²⁺ to the enzyme increased by ∼1 unit of the p<em>K</em>_a value of the flavin N₃ atom compared to the E_FAD-apo, consistent with metal-hydrate perturbing flavin electronic properties. In contrast, Ni²⁺ binding decreased the p<em>K</em>_a value, consistent with flavin N₃ atom deprotonating before the Ni²⁺-hydrate in the enzyme active site. These findings reveal that metal ion substitution has minimal impact on the electronic properties of the flavin and the overall structural integrity of the enzyme, highlighting the potential use of metal-substituted variants of the enzyme as biomimetic catalysts.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"769 ","pages":"Article 110397"},"PeriodicalIF":3.8,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699543","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":"Uncoupling protein 1 deficiency leads to transcriptomic differences in livers of pregnancy female mice and aggravates hepatic steatosis","authors":"Gang Wei ,&nbsp;Feng-Jie Shen ,&nbsp;Jun-Li Liu ,&nbsp;Jian-Hua Zhao ,&nbsp;Fang-Yuan Yang ,&nbsp;Ruo-Qi Feng ,&nbsp;Jing Lu ,&nbsp;Chen-Yang Zhang ,&nbsp;Feng-Wei Wang ,&nbsp;Bei-Dong Chen ,&nbsp;Xin Ding ,&nbsp;Jin-Kui Yang","doi":"10.1016/j.abb.2025.110395","DOIUrl":"10.1016/j.abb.2025.110395","url":null,"abstract":"<div><div>Pregnancy requires the coordination of metabolically active organs to support maternal nutrition and fetal growth. However, the metabolic cross-talk between adipose tissue and liver in females during pregnancy is still less clear. In this study, we evaluated the metabolic adaptations and phenotypes of liver in response to pregnancy-associated metabolic stress, particularly in the context of genetic ablation of Uncoupling protein 1 (<em>Ucp1)</em>-mediated catabolic circuit. Our results revealed that <em>Ucp1</em> deficiency (UCP1 knockout, KO) mice during late pregnancy exhibited significantly deteriorated metabolic phenotypes, including hepatic steatosis and whole-body glucose and lipid homeostasis, as compared to <em>Ucp1</em> deficiency or normal pregnancy mice. However, non-pregnant <em>Ucp1</em> deficiency mice displayed nearly normal metabolic phenotypes and structure alterations similar to those of littermate controls. Moreover, transcriptomic analyses by RNA sequencing (RNA-seq) clearly revealed that <em>Ucp1</em> deficiency led to a significant liver metabolic remodeling of differentially express genes (DEGs) before and especially during pregnancy. Consistently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses demonstrated the potential altered functions and signaling pathways, including metabolic dysfunctions in ribosome, oxidative phosphorylation, etc. Importantly, as derived from trend analyses of DEGs, our results further revealed the distinct expression pattern of each subcluster, which coincided with potential biological functions and relevant signaling pathways. The findings in the present study might provide valuable insights into the molecular mechanism of metabolic dysfunction-associated fatty liver disease (MAFLD) during pregnancy. Additionally, our data may provide a novel animal model of MAFLD, thus facilitating its potential therapies.</div></div><div><h3>New &amp; noteworthy</h3><div>Genetic ablation of <em>Ucp1</em> during pregnancy increases hepatic steatosis and deteriorated whole-body glucose and lipid homeostasis. Moreover, changes in hepatic gene expression are closely associated with metabolic dysfunctions in ribosome and oxidative phosphorylation. This work highlights the therapeutic potential of targeting UCP1- mediated catabolic circuit between adipose and liver during pregnancy, and the utility of RNA-seq analysis to reveal valuable information for the distinct expression pattern of each subcluster that contribute to pregnancy-dependent MASLD progression.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"768 ","pages":"Article 110395"},"PeriodicalIF":3.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690878","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":"Naringin in repairing articular cartilage injury by activating TGF-β/Smad signaling pathway to attenuate inflammatory response","authors":"Tiancheng Lyu ,&nbsp;Xiangchun Liu ,&nbsp;Yuxuan Liu ,&nbsp;Zheng Yang ,&nbsp;Pengyang Li ,&nbsp;Yingdong Lu ,&nbsp;Pengyuan Zhao ,&nbsp;Jing Chen ,&nbsp;Chao Ye","doi":"10.1016/j.abb.2025.110396","DOIUrl":"10.1016/j.abb.2025.110396","url":null,"abstract":"<div><div>Naringin protects cartilage and attenuates inflammation. This study investigated the mechanism by which naringin activates the TGF-β/Smad signaling pathway to attenuate the inflammatory response and repair rabbit articular cartilage injury. A ring bone extraction drill was used to create a rabbit articular cartilage injury model. Sixteen Japanese white rabbits were divided into Sham, Mod, Nar, and Con groups and treated for 12 weeks. Compared with the Mod group, obvious signs of morphological and structural repair of cartilage injury were observed in the Nar group. The ICRS, BV/TV, and BS/TV scores increased, whereas the Wakitani and Tb.Sp scores decreased. Furthermore, ADAMTS-5 levels were significantly reduced, and TGF-β1 levels were significantly increased. The average light density of P-Smad3 in the repaired tissue was significantly elevated, whereas that of MMP-13 was significantly reduced. Compared with that in the Sham group, the transcription and expression levels of TβRII, type II collagen, P-TβRII, and P-Smad2 in the repair tissues of the Mod group were lower. This was reversed in the Nar group. Therefore, naringin administration can improve the morphology and structure of articular cartilage injury, reduce the concentration and expression levels of pro-inflammatory factors in the joint fluid and repair tissues, and increase the concentrations and expression levels of anti-inflammatory factors in the joint fluid and repair tissues. Thus, naringin exerts a positive effect by reducing the inflammatory response and repairing articular cartilage injury. This mechanism is closely related to the activation of the TGF-β/Smad signaling pathway.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"768 ","pages":"Article 110396"},"PeriodicalIF":3.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690873","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":"Insights from selenoprotein I mouse models for understanding biological roles of this enzyme","authors":"Lance G.A. Nunes,&nbsp;Chi Ma,&nbsp;Matthew W. Pitts,&nbsp;Peter R. Hoffmann","doi":"10.1016/j.abb.2025.110394","DOIUrl":"10.1016/j.abb.2025.110394","url":null,"abstract":"<div><div>Selenoprotein I (selenoi) is a metabolic enzyme expressed in a wide variety of tissues that catalyzes the transfer of the ethanolamine phosphate group from CDP-ethanolamine to lipid acceptors to generate ethanolamine phospholipids. It is a member of the selenoprotein family, a class of proteins that mostly play fundamental roles in redox homeostasis and are defined by the co-translational incorporation of selenium in the form of selenocysteine. Loss-of-function mutations in the human SELENOI gene have been found in rare cases leading to a complex form of hereditary spastic paraplegia. Understanding the roles of this selenoprotein and its phospholipid products in different cell types has benefited from the development of mouse models. In particular, global and conditional knockout (KO) of the Selenoi gene in mice has enabled a more complete picture to emerge of how this important selenoprotein is integrated into metabolic pathways. These data have revealed how Selenoi loss-of-function affects embryogenesis, neurodevelopment, the immune system and liver physiology. This review summarizes the insights gained through mouse model experiments and the current understanding the different physiological roles played by this selenoprotein.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"768 ","pages":"Article 110394"},"PeriodicalIF":3.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662374","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":"Therapeutic effects and mechanisms of alcohol extracts from Polygala fallax Hemsl on endometriosis in rats","authors":"Si Yuwen ,&nbsp;Qian Zheng ,&nbsp;Chunhong Liao ,&nbsp;Lijuan Wei ,&nbsp;Sufang Yang ,&nbsp;Ning Li","doi":"10.1016/j.abb.2025.110393","DOIUrl":"10.1016/j.abb.2025.110393","url":null,"abstract":"<div><div>Endometriosis is a chronic estrogen-dependent inflammatory disease that significantly affects women's health. <em>Polygala fallax Hemsl.</em> (PFH), a traditional Zhuang medicine, has been frequently used for gynecological disorders. This study investigated the therapeutic effects and mechanisms of the alcohol extract of <em>Polygala fallax Hemsl.</em> (ae-PFH) in a rat model of endometriosis, as well as its potential for combination therapy. SD rats were divided into seven groups: control, model, PFH, mifepristone, PFH combined with mifepristone, exosomes, and PFH combined with exosomes. After 21 days of treatment, body weight, organ coefficients, and histopathological changes in uterine and ovarian tissues were analyzed. UPLC-Q-Exactive Orbitrap-MS identified active components in ae-PFH and serum samples, followed by molecular docking with key disease target proteins. Serum levels of inflammatory cytokines and hormones were measured using ELISA, while protein and mRNA expression of key regulatory factors were assessed via Western blot and q-PCR. Ae-PFH reduced lesion size and suppressed inflammation, angiogenesis, and pain by inhibitied the PI3K/AKT pathway. Additionally, in combination therapy, ae-PFH significantly enhanced therapeutic effects of mifepristone or exosomes derived from umbilical cord mesenchymal stem cells. These findings indicated that ae-PFH presentd a promising medical method for the treatment of endometriosis, exhibiting innovative potentiality for combination therapy.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"768 ","pages":"Article 110393"},"PeriodicalIF":3.8,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639388","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}