Pub Date : 2025-10-29DOI: 10.1016/j.abb.2025.110652
Yue Lai , Shushan Guo , Qiongwei Tang , Gaomei Chang , Hui Zhang , Bo Li , Qilin Feng , Ke Hu , Zhijian Xu , Xuejie Gao , Qikai Zhang , Hongfei Yi , Dongliang Song , Yifei Zhang , Yu Peng , Haiyan Cai , Weiliang Zhu , Jumei Shi
{"title":"Corrigendum to “Dihydrocelastrol induces cell death and suppresses angiogenesis through BCR/AP-1/junb signalling in diffuse large B cell lymphoma” [Arch. Biochem. Biophys. 754 (2024) 109929]","authors":"Yue Lai , Shushan Guo , Qiongwei Tang , Gaomei Chang , Hui Zhang , Bo Li , Qilin Feng , Ke Hu , Zhijian Xu , Xuejie Gao , Qikai Zhang , Hongfei Yi , Dongliang Song , Yifei Zhang , Yu Peng , Haiyan Cai , Weiliang Zhu , Jumei Shi","doi":"10.1016/j.abb.2025.110652","DOIUrl":"10.1016/j.abb.2025.110652","url":null,"abstract":"","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"776 ","pages":"Article 110652"},"PeriodicalIF":3.0,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145399652","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}
C-X-C motif chemokine ligand 17 (CXCL17) is a chemoattractant whose receptor remains controversial. While recent studies identified CXCL17 as an agonist of G protein-coupled receptor 25 (GPR25), it was also reported to activate MAS-related GPR family member X2 (MRGPRX2), a member of MAS-related G protein-coupled receptors (MRGPRs), though this finding has not yet been reproduced by other laboratories. In this study, we confirmed that micromolar concentrations of human CXCL17 activate human MRGPRX2 in transfected human embryonic kidney (HEK) 293T cells using a NanoLuc Binary Technology (NanoBiT)-based β-arrestin recruitment assay. We further demonstrated that human CXCL17 also activates MRGPRX1 and MAS1 among 10 human MRGPRs in the same assay. CXCL17 could also induce chemotactic movement of transfected HEK293T cells expressing MRGPRX2, MRGPRX1, or MAS1. However, removal of C-terminal residues from CXCL17 did not affect its activation of these three MRGPRs, even though this region is essential for GPR25 activation. These results suggest that CXCL17 activates MRGPRX2, MRGPRX1, and MAS1 through a mechanism distinct from GPR25 activation. Further investigation is needed to determine whether these MRGPRs mediate the in vivo functions of CXCL17.
{"title":"CXCL17 activates three MAS-related G protein-coupled receptors independently of its conserved C-terminal fragment","authors":"Wen-Feng Hu, Juan-Juan Wang, Jie Yu, Ya-Li Liu, Zeng-Guang Xu, Zhan-Yun Guo","doi":"10.1016/j.abb.2025.110666","DOIUrl":"10.1016/j.abb.2025.110666","url":null,"abstract":"<div><div>C-X-C motif chemokine ligand 17 (CXCL17) is a chemoattractant whose receptor remains controversial. While recent studies identified CXCL17 as an agonist of G protein-coupled receptor 25 (GPR25), it was also reported to activate MAS-related GPR family member X2 (MRGPRX2), a member of MAS-related G protein-coupled receptors (MRGPRs), though this finding has not yet been reproduced by other laboratories. In this study, we confirmed that micromolar concentrations of human CXCL17 activate human MRGPRX2 in transfected human embryonic kidney (HEK) 293T cells using a NanoLuc Binary Technology (NanoBiT)-based β-arrestin recruitment assay. We further demonstrated that human CXCL17 also activates MRGPRX1 and MAS1 among 10 human MRGPRs in the same assay. CXCL17 could also induce chemotactic movement of transfected HEK293T cells expressing MRGPRX2, MRGPRX1, or MAS1. However, removal of C-terminal residues from CXCL17 did not affect its activation of these three MRGPRs, even though this region is essential for GPR25 activation. These results suggest that CXCL17 activates MRGPRX2, MRGPRX1, and MAS1 through a mechanism distinct from GPR25 activation. Further investigation is needed to determine whether these MRGPRs mediate the <em>in vivo</em> functions of CXCL17.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"775 ","pages":"Article 110666"},"PeriodicalIF":3.0,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145407900","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}
Pub Date : 2025-10-28DOI: 10.1016/j.abb.2025.110667
Sheng Lin, Junbin Chen
Background
Dysregulated microRNAs are implicated in the acute cerebral infarction (ACI) pathogenesis.
Aim
This study investigated the clinical significance and mechanisms of miR-943 in ACI.
Methods
Serum miR-943 levels were measured using RT-qPCR in 132 ACI patients and 135 healthy controls (HC). Diagnostic potential was evaluated by ROC analysis. Prognosis was assessed using 90-day mRS scores. Correlations with clinical parameters were analyzed using Pearson's/Spearman's tests. Multivariate logistic regression identified outcome predictors. Bioinformatic prediction and experimental validation (dual-luciferase, RIP assays) identified miR-943 targets. An OGD/R model in BV-2 microglia simulated ischemia-reperfusion. Effects of miR-943 inhibitors and si-BDNF on viability (CCK-8), apoptosis (flow cytometry), and inflammation (ELISA) were assessed.
Results
ACI patients exhibited significantly elevated serum miR-943 expression and reduced BDNF levels versus HC. miR-943 showed high diagnostic value (AUC = 0.909, sensitivity 85.6 %, specificity 83.7 %). MiR-943 expression correlated positively with SBP, DBP, FBG, Hcy, NIHSS score, and infarct volume. Patients with a poor prognosis exhibited significantly higher miR-943 expression levels. Multivariate analysis identified high expression of miR-943 as an independent risk factor for poor outcome. BDNF was validated as a direct miR-943 target gene. OGD/R increased miR-943 expression, suppressed proliferation, promoted apoptosis, and enhanced the expression of inflammatory factors in BV-2 cells. Inhibiting miR-943 expression reversed these detrimental effects, enhancing proliferation and reducing apoptosis/inflammation. Critically, BDNF knockdown abolished the protective effects of miR-943 inhibition.
Conclusion
Serum miR-943 is a promising diagnostic and prognostic biomarker for ACI. It exerts pathological effects by post-transcriptionally suppressing BDNF. Targeting the miR-943/BDNF axis represents a potential therapeutic strategy.
{"title":"Clinical value of serum miR-943 as a diagnostic and prognostic biomarker for acute cerebral infarction and its mechanism of action via targeting BDNF","authors":"Sheng Lin, Junbin Chen","doi":"10.1016/j.abb.2025.110667","DOIUrl":"10.1016/j.abb.2025.110667","url":null,"abstract":"<div><h3>Background</h3><div>Dysregulated microRNAs are implicated in the acute cerebral infarction (ACI) pathogenesis.</div></div><div><h3>Aim</h3><div>This study investigated the clinical significance and mechanisms of miR-943 in ACI.</div></div><div><h3>Methods</h3><div>Serum miR-943 levels were measured using RT-qPCR in 132 ACI patients and 135 healthy controls (HC). Diagnostic potential was evaluated by ROC analysis. Prognosis was assessed using 90-day mRS scores. Correlations with clinical parameters were analyzed using Pearson's/Spearman's tests. Multivariate logistic regression identified outcome predictors. Bioinformatic prediction and experimental validation (dual-luciferase, RIP assays) identified miR-943 targets. An OGD/R model in BV-2 microglia simulated ischemia-reperfusion. Effects of miR-943 inhibitors and si-BDNF on viability (CCK-8), apoptosis (flow cytometry), and inflammation (ELISA) were assessed.</div></div><div><h3>Results</h3><div>ACI patients exhibited significantly elevated serum miR-943 expression and reduced BDNF levels versus HC. miR-943 showed high diagnostic value (AUC = 0.909, sensitivity 85.6 %, specificity 83.7 %). MiR-943 expression correlated positively with SBP, DBP, FBG, Hcy, NIHSS score, and infarct volume. Patients with a poor prognosis exhibited significantly higher miR-943 expression levels. Multivariate analysis identified high expression of miR-943 as an independent risk factor for poor outcome. BDNF was validated as a direct miR-943 target gene. OGD/R increased miR-943 expression, suppressed proliferation, promoted apoptosis, and enhanced the expression of inflammatory factors in BV-2 cells. Inhibiting miR-943 expression reversed these detrimental effects, enhancing proliferation and reducing apoptosis/inflammation. Critically, BDNF knockdown abolished the protective effects of miR-943 inhibition.</div></div><div><h3>Conclusion</h3><div>Serum miR-943 is a promising diagnostic and prognostic biomarker for ACI. It exerts pathological effects by post-transcriptionally suppressing BDNF. Targeting the miR-943/BDNF axis represents a potential therapeutic strategy.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"775 ","pages":"Article 110667"},"PeriodicalIF":3.0,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145407760","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}
Pub Date : 2025-10-28DOI: 10.1016/j.abb.2025.110645
Ayushi Saini, Aishik Sil, Satyajit Beura, Amit Kumar Das
Mycobacterium tuberculosis (Mtb) remains a major global health threat due to its survival under host-induced stress and the rise of drug-resistant strains. One critical factor contributing to this resilience is its ability to efficiently repair DNA damage. To survive double-stranded DNA breaks, Mtb utilizes two pathways: homologous recombination (HR) and non-homologous end joining (NHEJ). During dormancy, when HR is less active, Mtb predominantly relies on NHEJ, a pathway involving Ku and LigaseD. LigaseD catalyses DNA ligation through its ligase domain (LigDom), which comprises two subdomains: the NTase, harboring the ATP-binding site essential for adenylation, and the OB domain, which interacts with DNA. LigDom is highly conserved and exhibits low mutation rates in resistant strains, making it an attractive drug target. Using a structure-based drug repurposing approach, FDA-approved drugs were screened, identifying L-756423 as a potent inhibitor with a lowest binding free energy. Molecular dynamics simulation of the L-756423 bound LigDom complex reveals a stable domain structure with significant fluctuations in the interdomain region, suggesting movement in the OB domain that may support efficient binding. To validate these findings, Indinavir, a clinically approved HIV protease inhibitor with structural similarity to L-756423, was selected for experimental testing. Indinavir induces conformational flexibility in LigDom, and also competitively inhibits ATP binding thus blocking the adenylation. Functional microbiological assays confirmed that under oxidative stress, when NHEJ is critical, indinavir-treated cells displayed reduced survival, consistent with impaired DNA repair. These findings indicate that L-756423/Indinavir may hold therapeutic potential against latent tuberculosis and provide a rationale for further experimental investigation.
{"title":"Structure-based drug repurposing and experimental validation of inhibitors targeting LigaseD from Mycobacterium tuberculosis","authors":"Ayushi Saini, Aishik Sil, Satyajit Beura, Amit Kumar Das","doi":"10.1016/j.abb.2025.110645","DOIUrl":"10.1016/j.abb.2025.110645","url":null,"abstract":"<div><div><em>Mycobacterium tuberculosis</em> (Mtb) remains a major global health threat due to its survival under host-induced stress and the rise of drug-resistant strains. One critical factor contributing to this resilience is its ability to efficiently repair DNA damage. To survive double-stranded DNA breaks, Mtb utilizes two pathways: homologous recombination (HR) and non-homologous end joining (NHEJ). During dormancy, when HR is less active, Mtb predominantly relies on NHEJ, a pathway involving Ku and LigaseD. LigaseD catalyses DNA ligation through its ligase domain (LigDom), which comprises two subdomains: the NTase, harboring the ATP-binding site essential for adenylation, and the OB domain, which interacts with DNA. LigDom is highly conserved and exhibits low mutation rates in resistant strains, making it an attractive drug target. Using a structure-based drug repurposing approach, FDA-approved drugs were screened, identifying L-756423 as a potent inhibitor with a lowest binding free energy. Molecular dynamics simulation of the L-756423 bound LigDom complex reveals a stable domain structure with significant fluctuations in the interdomain region, suggesting movement in the OB domain that may support efficient binding. To validate these findings, Indinavir, a clinically approved HIV protease inhibitor with structural similarity to L-756423, was selected for experimental testing. Indinavir induces conformational flexibility in LigDom, and also competitively inhibits ATP binding thus blocking the adenylation. Functional microbiological assays confirmed that under oxidative stress, when NHEJ is critical, indinavir-treated cells displayed reduced survival, consistent with impaired DNA repair. These findings indicate that L-756423/Indinavir may hold therapeutic potential against latent tuberculosis and provide a rationale for further experimental investigation.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"775 ","pages":"Article 110645"},"PeriodicalIF":3.0,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145407871","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}
Pub Date : 2025-10-27DOI: 10.1016/j.abb.2025.110665
Mutsumi Yoshida , Yuya Hanazono , Nobutaka Numoto , Saaya Yabuno , Nobutoshi Ito , Takachika Azuma , Masayuki Oda
The phenomenon in which the antibody affinity for T cell-dependent antigens increases through multiple rounds of somatic hypermutation (SHM) is referred to as affinity maturation. The elucidation of the structural and physical properties of antibodies obtained at various stages of the affinity maturation process can help us understand the molecular recognition mechanism of proteins in general. For this purpose, we used anti-(4-hydroxy-3-nitrophenyl)acetyl (NP) single-chain (scFv) antibodies, prepared from the parent antibodies F8, B2, C6, and E11, and analyzed the crystal structures either in the absence or presence of NP or (4-hydroxy-3,5-dinitrophenyl)acetyl (NNP). Comparison of the structures revealed that the antibodies shared a common antigen recognition architecture consisting of residues with basic side chains, Arg50H and Lys58H/Arg58H, in addition to those at the junctional positions of gene segments, Trp96L and Tyr95H or His100BH. These residues are responsible for the recognition of antigenic determinants, nitro-, hydroxyl- and phenylacetyl-groups, through hydrogen bond formation. Second, the Trp33H to Leu33H mutation seemed to strengthen the interaction because the antigen was closer to the combining site. Finally, analysis of NP and NNP complexes showed little difference in the antigen recognition modes and in the overall structures of the complementarity-determining regions between C6 and E11 scFvs. It was suggested that the replacement of residues by SHM provided a unique binding site for each antibody by fine tuning the microenvironment without disturbing specificity.
{"title":"Structural basis of affinity maturation of anti-(4-hydroxy-3-nitrophenyl)acetyl antibodies","authors":"Mutsumi Yoshida , Yuya Hanazono , Nobutaka Numoto , Saaya Yabuno , Nobutoshi Ito , Takachika Azuma , Masayuki Oda","doi":"10.1016/j.abb.2025.110665","DOIUrl":"10.1016/j.abb.2025.110665","url":null,"abstract":"<div><div>The phenomenon in which the antibody affinity for T cell-dependent antigens increases through multiple rounds of somatic hypermutation (SHM) is referred to as affinity maturation. The elucidation of the structural and physical properties of antibodies obtained at various stages of the affinity maturation process can help us understand the molecular recognition mechanism of proteins in general. For this purpose, we used anti-(4-hydroxy-3-nitrophenyl)acetyl (NP) single-chain (scFv) antibodies, prepared from the parent antibodies F8, B2, C6, and E11, and analyzed the crystal structures either in the absence or presence of NP or (4-hydroxy-3,5-dinitrophenyl)acetyl (NNP). Comparison of the structures revealed that the antibodies shared a common antigen recognition architecture consisting of residues with basic side chains, Arg50<sup>H</sup> and Lys58<sup>H</sup>/Arg58<sup>H</sup>, in addition to those at the junctional positions of gene segments, Trp96<sup>L</sup> and Tyr95<sup>H</sup> or His100B<sup>H</sup>. These residues are responsible for the recognition of antigenic determinants, nitro-, hydroxyl- and phenylacetyl-groups, through hydrogen bond formation. Second, the Trp33<sup>H</sup> to Leu33<sup>H</sup> mutation seemed to strengthen the interaction because the antigen was closer to the combining site. Finally, analysis of NP and NNP complexes showed little difference in the antigen recognition modes and in the overall structures of the complementarity-determining regions between C6 and E11 scFvs. It was suggested that the replacement of residues by SHM provided a unique binding site for each antibody by fine tuning the microenvironment without disturbing specificity.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"775 ","pages":"Article 110665"},"PeriodicalIF":3.0,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145399720","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}
Pub Date : 2025-10-26DOI: 10.1016/j.abb.2025.110664
Cheng-Yi Chang , Chih-Cheng Wu , Ping-Ho Pan , Chung-Yuh Tzeng , Tung-Min Yu , Shih-Yi Lin , Ya-Yu Wang , Su-Lan Liao , Chun-Jung Chen
Peripheral neuropathy is a common and debilitating complication of chemotherapy, characterized by nociceptive hypersensitivity with concurrent mitochondrial dysfunction, oxidative stress, and inflammation. Although nutraceutical supplement with Docosahexaenoic Acid (DHA) improves cancer treatment outcome and complications, molecular mechanisms responsible for beneficial effects are not well understood. Using a Sprague-Dawley rat model of vincristine-induced peripheral neuropathy, herein, we provide behavioral, histological, biochemical, and molecular evidence showing that DHA pretreatment alleviates chemotherapy-induced peripheral neuropathy. Nociceptive hypersensitivity and spinal cord dorsal horn neurodegeneration were accompanied by spinal cord dorsal horn nociceptive Interleukin-6 expression, NADPH oxidase 2 elevation, malondialdehyde production, superoxide dismutase activity inhibition, and glutathione reduction as well as circulating immune cell activation. In parallel, reduction of protein expression crucial to mitochondrial biogenesis, fission, and mitophagy as well as antioxidative defense and anti-inflammation was seen. DHA had alleviative effects on vincristine-induced changes. In assessing molecular targets, Peroxisome Proliferator-Activated Receptor γ (PPAR-γ) represented a surrogate candidate to coordinate action cascades in alleviating mitochondrial dysfunction, oxidative stress, and inflammation when activated by DHA. Although there remain limitations and further investigation is warranted, DHA supplementation is proposed as a protective strategy to alleviate chemotherapy-induced peripheral neuropathy. Our findings further imply that the mechanisms by which DHA is able to induce pain relief, directly or indirectly, could involve mitochondrial dysfunction, oxidative stress, and inflammation.
{"title":"Docosahexaenoic acid improved vincristine-induced peripheral neuropathy in a rat model","authors":"Cheng-Yi Chang , Chih-Cheng Wu , Ping-Ho Pan , Chung-Yuh Tzeng , Tung-Min Yu , Shih-Yi Lin , Ya-Yu Wang , Su-Lan Liao , Chun-Jung Chen","doi":"10.1016/j.abb.2025.110664","DOIUrl":"10.1016/j.abb.2025.110664","url":null,"abstract":"<div><div>Peripheral neuropathy is a common and debilitating complication of chemotherapy, characterized by nociceptive hypersensitivity with concurrent mitochondrial dysfunction, oxidative stress, and inflammation. Although nutraceutical supplement with Docosahexaenoic Acid (DHA) improves cancer treatment outcome and complications, molecular mechanisms responsible for beneficial effects are not well understood. Using a Sprague-Dawley rat model of vincristine-induced peripheral neuropathy, herein, we provide behavioral, histological, biochemical, and molecular evidence showing that DHA pretreatment alleviates chemotherapy-induced peripheral neuropathy. Nociceptive hypersensitivity and spinal cord dorsal horn neurodegeneration were accompanied by spinal cord dorsal horn nociceptive Interleukin-6 expression, NADPH oxidase 2 elevation, malondialdehyde production, superoxide dismutase activity inhibition, and glutathione reduction as well as circulating immune cell activation. In parallel, reduction of protein expression crucial to mitochondrial biogenesis, fission, and mitophagy as well as antioxidative defense and anti-inflammation was seen. DHA had alleviative effects on vincristine-induced changes. In assessing molecular targets, Peroxisome Proliferator-Activated Receptor γ (PPAR-γ) represented a surrogate candidate to coordinate action cascades in alleviating mitochondrial dysfunction, oxidative stress, and inflammation when activated by DHA. Although there remain limitations and further investigation is warranted, DHA supplementation is proposed as a protective strategy to alleviate chemotherapy-induced peripheral neuropathy. Our findings further imply that the mechanisms by which DHA is able to induce pain relief, directly or indirectly, could involve mitochondrial dysfunction, oxidative stress, and inflammation.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"775 ","pages":"Article 110664"},"PeriodicalIF":3.0,"publicationDate":"2025-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145386215","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}
Pub Date : 2025-10-25DOI: 10.1016/j.abb.2025.110653
Zhaohui Yang , Jiawen Hao , Zhongyu Ma , Yunxiao Xie , Ruixue Zhang , Xuewei Yin , Guimin Wang , Yinqiao Zhang , Miao Zhang , Xuan Zhang , Dadong Guo , Hongsheng Bi
Objective
To explore the influence of the activated Notch1 signaling pathway on choroidal tissue fibrosis in experimental myopia.
Methods
Right eyes were fitted with a −6.0D lens to create experimental myopia. Ocular parameters, choroidal thickness, and blood flow were assessed after the injection of shRNA-Notch1 and the Notch1 pathway inhibitor DAPT into the vitreous cavity. Changes in blood flow in the choroid were observed using optical coherence tomography angiography (OCTA). The expression levels of molecules associated with the Notch1 signaling pathway were assessed at both the gene and protein levels. Additionally, we examined the choroidal thickness, level of choroidal fibrosis, and level of apoptosis using hematoxylin and eosin (H&E) staining, Masson staining, and TdT-mediated dUTP Nick-End Labeling (TUNEL).
Results
Compared with the NC group, the LIM group presented a substantial decrease in diopter, increased optical axis length, decreased choroidal thickness, and significantly reduced blood perfusion. qPCR and Western blotting revealed that the expression levels of Notch1, HES1, DLL1, TGF-β, α-SMA, and collagen Ⅰ in the LIM group were considerably greater than those in the NC group. Masson staining confirmed that fibrosis occurred in the choroidal tissue of the LIM group. Vitreous injection of shRNA-Notch1 and DAPT attenuated fibrosis, thereby controlling myopia progression.
Conclusion
Activation of the Notch1 signaling pathway leads to choroidal physiological dysfunction and elongated optical axis length, driving the progression of myopia. By inhibiting the Notch1 signaling pathway, shRNA-Notch1 can suppress optical axis elongation, increase choroidal thickness, and attenuate choroidal fibrosis, thus inhibiting the progression of myopia.
{"title":"Aggravated choroidal tissue fibrosis in experimental myopia is involved in activation of the Notch1 signaling pathway","authors":"Zhaohui Yang , Jiawen Hao , Zhongyu Ma , Yunxiao Xie , Ruixue Zhang , Xuewei Yin , Guimin Wang , Yinqiao Zhang , Miao Zhang , Xuan Zhang , Dadong Guo , Hongsheng Bi","doi":"10.1016/j.abb.2025.110653","DOIUrl":"10.1016/j.abb.2025.110653","url":null,"abstract":"<div><h3>Objective</h3><div>To explore the influence of the activated Notch1 signaling pathway on choroidal tissue fibrosis in experimental myopia.</div></div><div><h3>Methods</h3><div>Right eyes were fitted with a −6.0D lens to create experimental myopia. Ocular parameters, choroidal thickness, and blood flow were assessed after the injection of shRNA-Notch1 and the Notch1 pathway inhibitor DAPT into the vitreous cavity. Changes in blood flow in the choroid were observed using optical coherence tomography angiography (OCTA). The expression levels of molecules associated with the Notch1 signaling pathway were assessed at both the gene and protein levels. Additionally, we examined the choroidal thickness, level of choroidal fibrosis, and level of apoptosis using hematoxylin and eosin (H&E) staining, Masson staining, and TdT-mediated dUTP Nick-End Labeling (TUNEL).</div></div><div><h3>Results</h3><div>Compared with the NC group, the LIM group presented a substantial decrease in diopter, increased optical axis length, decreased choroidal thickness, and significantly reduced blood perfusion. qPCR and Western blotting revealed that the expression levels of Notch1, HES1, DLL1, TGF-β, α-SMA, and collagen Ⅰ in the LIM group were considerably greater than those in the NC group. Masson staining confirmed that fibrosis occurred in the choroidal tissue of the LIM group. Vitreous injection of shRNA-Notch1 and DAPT attenuated fibrosis, thereby controlling myopia progression.</div></div><div><h3>Conclusion</h3><div>Activation of the Notch1 signaling pathway leads to choroidal physiological dysfunction and elongated optical axis length, driving the progression of myopia. By inhibiting the Notch1 signaling pathway, shRNA-Notch1 can suppress optical axis elongation, increase choroidal thickness, and attenuate choroidal fibrosis, thus inhibiting the progression of myopia.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"775 ","pages":"Article 110653"},"PeriodicalIF":3.0,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145414929","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}
Pub Date : 2025-10-24DOI: 10.1016/j.abb.2025.110650
Elena G. Varlamova , Vladimir V. Rogachev , Sergey V. Gudkov , Egor A. Turovsky
Background
The neuroprotective potential of tellurium nanoparticles (TeNPs) remains critically underexplored compared to their selenium analogues, despite their presumed physicochemical similarities. A significant limitation has been the absence of a reliable method for producing highly stable, monodisperse TeNPs without chemical contaminants for robust biological assessment.
Key results
In this study, we developed a novel laser ablation protocol to synthesize stable spherical TeNPs with two distinct diameters (10 nm and 100 nm). We comprehensively investigated their diameter-dependent effects on primary cortical cells under excitotoxicity and ischemia models. Our key finding reveals a striking dichotomy of effects: 100 nm-sized TeNPs conferred significant cytoprotection against glutamate excitotoxicity, primarily by suppressing necrotic cell death. In contrast, 10 nm-sized TeNPs exacerbated oxidative stress, upregulated pro-apoptotic and pro-inflammatory gene expression, and failed to provide protection in either injury model. Furthermore, 100 nm-sized TeNPs uniquely modulated selenoprotein gene expression patterns under ischemic stress. Surprisingly, particles of neither diameter protected against oxygen-glucose deprivation (OGD), while 100 nm-sized TeNPs potentiated ischemia-induced calcium overload.
Originality and significance
This work is the first to (1) employ laser-ablated TeNPs in neurobiological research, (2) demonstrate a complete reversal of neuroprotective outcomes based solely on nanoparticle size, and (3) establish correlations between TeNP-induced effects and specific alterations in calcium signaling, reactive oxygen species (ROS) production, and gene expression profiles in brain cells. Our findings underscore that nanoparticle size is a critical, non-negotiable parameter determining the therapeutic-to-toxic outcome of TeNPs in the brain. This provides a crucial foundation for the future design of nanotherapeutic agents for neurological disorders.
{"title":"From toxicity to protection: Size-specific effects of tellurium nanoparticles on cortical cell survival","authors":"Elena G. Varlamova , Vladimir V. Rogachev , Sergey V. Gudkov , Egor A. Turovsky","doi":"10.1016/j.abb.2025.110650","DOIUrl":"10.1016/j.abb.2025.110650","url":null,"abstract":"<div><h3>Background</h3><div>The neuroprotective potential of tellurium nanoparticles (TeNPs) remains critically underexplored compared to their selenium analogues, despite their presumed physicochemical similarities. A significant limitation has been the absence of a reliable method for producing highly stable, monodisperse TeNPs without chemical contaminants for robust biological assessment.</div></div><div><h3>Key results</h3><div>In this study, we developed a novel laser ablation protocol to synthesize stable spherical TeNPs with two distinct diameters (10 nm and 100 nm). We comprehensively investigated their diameter-dependent effects on primary cortical cells under excitotoxicity and ischemia models. Our key finding reveals a striking dichotomy of effects: 100 nm-sized TeNPs conferred significant cytoprotection against glutamate excitotoxicity, primarily by suppressing necrotic cell death. In contrast, 10 nm-sized TeNPs exacerbated oxidative stress, upregulated pro-apoptotic and pro-inflammatory gene expression, and failed to provide protection in either injury model. Furthermore, 100 nm-sized TeNPs uniquely modulated selenoprotein gene expression patterns under ischemic stress. Surprisingly, particles of neither diameter protected against oxygen-glucose deprivation (OGD), while 100 nm-sized TeNPs potentiated ischemia-induced calcium overload.</div></div><div><h3>Originality and significance</h3><div>This work is the first to (1) employ laser-ablated TeNPs in neurobiological research, (2) demonstrate a complete reversal of neuroprotective outcomes based solely on nanoparticle size, and (3) establish correlations between TeNP-induced effects and specific alterations in calcium signaling, reactive oxygen species (ROS) production, and gene expression profiles in brain cells. Our findings underscore that nanoparticle size is a critical, non-negotiable parameter determining the therapeutic-to-toxic outcome of TeNPs in the brain. This provides a crucial foundation for the future design of nanotherapeutic agents for neurological disorders.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"775 ","pages":"Article 110650"},"PeriodicalIF":3.0,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145414502","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}
Pub Date : 2025-10-24DOI: 10.1016/j.abb.2025.110646
Jessica Georgina Filisola-Villaseñor , Samuel Álvarez-Almazán , Omar Granados-Portillo , Alicia Cruz-Jiménez , Gustavo G. Medina-Mendoza , Dan Israel Zavala-Vargas , J. Armando Luján-Montelongo , Edgar Morales-Ríos , Viridiana Olin-Sandoval
Ornithine decarboxylase (ODC) catalyzes the first step in the polyamines (PAs) biosynthesis pathway. These biomolecules are polycations that participate in many cellular processes. However, the non-physiological increase of human ODC (HsODC) expression can lead to the accumulation of PAs, and consequently, to the development of various types of cancer. Despite several inhibitors of HsODC have been proposed for cancer treatment, only the administration of difluoromethylornithine (DFMO) has been accepted as a drug for preventing the relapse of neuroblastoma. Thus, the search for other HsODC inhibitors continues. Previously, an alternative l-lysine decarboxylase activity was described in yeast and rat ODC. In this work, we expressed and purified the recombinant HsODC. Then, we kinetically characterized the ornithine and lysine decarboxylase (LDC) activities of the enzyme with Vmax/KM of 25.4 and 0.353 mL min−1 mg protein−1, respectively. Then, we selected 30 lysine-analogues from 300 candidate ligands for HsODC by molecular docking. The binding of these thirty molecules to HsODC was evaluated through thermal shift assays (TSA), obtaining nine binding molecules. Finally, the HsODC kinetic inhibition assays demonstrated that 7 compounds can inhibit this enzyme in vitro (with Ki ranging from 3.8 nM to 523.5 μM). With our results, we suggest these compounds as candidates to be explored as HsODC inhibitors in cell lines and in vivo models.
鸟氨酸脱羧酶（ODC）催化多胺（PAs）生物合成途径的第一步。这些生物分子是参与许多细胞过程的聚合体。然而，人类ODC （HsODC）表达的非生理性增加可导致PAs的积累，从而导致各种类型癌症的发生。尽管已经提出了几种HsODC抑制剂用于癌症治疗，但只有二氟甲基鸟氨酸（DFMO）被接受为预防神经母细胞瘤复发的药物。因此，对其他HsODC抑制剂的研究仍在继续。以前，在酵母和大鼠ODC中描述了另一种赖氨酸脱羧酶活性。在这项工作中，我们表达和纯化了重组HsODC。然后，我们对该酶的鸟氨酸和赖氨酸脱羧酶（LDC）活性进行了动力学表征，Vmax/KM分别为25.4和0.353 mL min - 1 mg protein - 1。然后，通过分子对接，从300个HsODC候选配体中筛选出30个赖氨酸类似物。通过热移法（TSA）评估了这30个分子与HsODC的结合，获得了9个结合分子。最后，HsODC动力学抑制实验表明，7种化合物对该酶具有体外抑制作用（Ki范围为3.8 nM ~ 523.5 μM）。根据我们的结果，我们建议这些化合物作为细胞系和体内模型中HsODC抑制剂的候选物进行探索。
{"title":"Characterization of the lysine decarboxylase activity of human ornithine decarboxylase and identification of lysine-like inhibitors","authors":"Jessica Georgina Filisola-Villaseñor , Samuel Álvarez-Almazán , Omar Granados-Portillo , Alicia Cruz-Jiménez , Gustavo G. Medina-Mendoza , Dan Israel Zavala-Vargas , J. Armando Luján-Montelongo , Edgar Morales-Ríos , Viridiana Olin-Sandoval","doi":"10.1016/j.abb.2025.110646","DOIUrl":"10.1016/j.abb.2025.110646","url":null,"abstract":"<div><div>Ornithine decarboxylase (ODC) catalyzes the first step in the polyamines (PAs) biosynthesis pathway. These biomolecules are polycations that participate in many cellular processes. However, the non-physiological increase of human ODC (HsODC) expression can lead to the accumulation of PAs, and consequently, to the development of various types of cancer. Despite several inhibitors of HsODC have been proposed for cancer treatment, only the administration of difluoromethylornithine (DFMO) has been accepted as a drug for preventing the relapse of neuroblastoma. Thus, the search for other HsODC inhibitors continues. Previously, an alternative <span>l</span>-lysine decarboxylase activity was described in yeast and rat ODC. In this work, we expressed and purified the recombinant HsODC. Then, we kinetically characterized the ornithine and lysine decarboxylase (LDC) activities of the enzyme with V<sub>max</sub>/K<sub>M</sub> of 25.4 and 0.353 mL min<sup>−1</sup> mg protein<sup>−1</sup>, respectively. Then, we selected 30 lysine-analogues from 300 candidate ligands for HsODC by molecular docking. The binding of these thirty molecules to HsODC was evaluated through thermal shift assays (TSA), obtaining nine binding molecules. Finally, the HsODC kinetic inhibition assays demonstrated that 7 compounds can inhibit this enzyme <em>in vitro</em> (with Ki ranging from 3.8 nM to 523.5 μM). With our results, we suggest these compounds as candidates to be explored as HsODC inhibitors in cell lines and <em>in vivo</em> models.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"775 ","pages":"Article 110646"},"PeriodicalIF":3.0,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145414938","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}
Pub Date : 2025-10-24DOI: 10.1016/j.abb.2025.110649
Georges Hraoui, Mélanie Grondin, Khadija Rezki, Diana A. Averill-Bates
Hyperthermia is generally administered as an adjuvant to chemotherapy/radiotherapy and sensitizes tumors to these anticancer treatments. Repeated heat treatments (≥42 °C) cause development of transient thermotolerance, an adaptive survival response. This response can be mediated by upregulation of cellular defense pathways and remains unclear. We aim to clarify the mechanistic explanations behind activation of this response. In vitro, thermotolerance can be induced by mild heat stress at 40 °C and protects cells against subsequent lethal heat shock (≥42 °C). When HeLa cells were heated at 42 °C, cellular and mitochondrial superoxide and peroxide levels increased. Treatment with mitochondrial antioxidant MitoQ, or NADPH oxidase (NOX) inhibitor apocynin, decreased levels of reactive oxygen species (ROS) and apoptotic cell death, indicating that mitochondria and NOX are important sources of ROS at 42 °C. Mild heat stress at 40 °C increased production of ROS, which are thought to activate the adaptive response, and reduce subsequent cell death at 42 °C. Our results show that heat-derived ROS are linked to expression of master antioxidant regulator Nrf2. When Nrf2 was overexpressed or knocked down, Nrf2 expression was directly associated with protective ability of the adaptive response induced by mild heat stress (40 °C). Mitochondrial ROS were found to be essential in mediating Nrf2-dependent thermotolerance, because MitoQ treatment prior to exposure to 40 °C reduced Nrf2 levels and dissipated the subsequent protective effect of thermotolerance against toxicity at 42 °C. Our study demonstrates that specific sources of ROS had biologically different implications in activating Nrf2, underlining potential therapeutic targets that may contribute to thermotolerance in anticancer treatments.
{"title":"Thermotolerance induced by non-lethal heat shock at 40 °C is activated by mitochondrial ROS and is Nrf2-dependent","authors":"Georges Hraoui, Mélanie Grondin, Khadija Rezki, Diana A. Averill-Bates","doi":"10.1016/j.abb.2025.110649","DOIUrl":"10.1016/j.abb.2025.110649","url":null,"abstract":"<div><div>Hyperthermia is generally administered as an adjuvant to chemotherapy/radiotherapy and sensitizes tumors to these anticancer treatments. Repeated heat treatments (≥42 °C) cause development of transient thermotolerance, an adaptive survival response. This response can be mediated by upregulation of cellular defense pathways and remains unclear. We aim to clarify the mechanistic explanations behind activation of this response. <em>In vitro</em>, thermotolerance can be induced by mild heat stress at 40 °C and protects cells against subsequent lethal heat shock (≥42 °C). When HeLa cells were heated at 42 °C, cellular and mitochondrial superoxide and peroxide levels increased. Treatment with mitochondrial antioxidant MitoQ, or NADPH oxidase (NOX) inhibitor apocynin, decreased levels of reactive oxygen species (ROS) and apoptotic cell death, indicating that mitochondria and NOX are important sources of ROS at 42 °C. Mild heat stress at 40 °C increased production of ROS, which are thought to activate the adaptive response, and reduce subsequent cell death at 42 °C. Our results show that heat-derived ROS are linked to expression of master antioxidant regulator Nrf2. When Nrf2 was overexpressed or knocked down, Nrf2 expression was directly associated with protective ability of the adaptive response induced by mild heat stress (40 °C). Mitochondrial ROS were found to be essential in mediating Nrf2-dependent thermotolerance, because MitoQ treatment prior to exposure to 40 °C reduced Nrf2 levels and dissipated the subsequent protective effect of thermotolerance against toxicity at 42 °C. Our study demonstrates that specific sources of ROS had biologically different implications in activating Nrf2, underlining potential therapeutic targets that may contribute to thermotolerance in anticancer treatments.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"775 ","pages":"Article 110649"},"PeriodicalIF":3.0,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145414939","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}
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