Pub Date : 2026-01-28DOI: 10.1016/j.bbrc.2026.153374
Yury B Slonimskiy, Daria A Lunegova, Andrey S Nikolaev, Ilya O Matyuta, Konstantin E Klementiev, Vladimir O Popov, Konstantin M Boyko, Ivan Yu Gushchin, Nikolai N Sluchanko
The recently discovered family of microalgal water-soluble astaxanthin-binding proteins (AstaPs) functions in carotenoid sequestration and transfer. We present the crystal structure and characterization of AstaP-pink1, a homolog from Scenedesmus sp. We show that despite low sequence identity with the known AstaP-orange1, AstaP-pink1 also binds various xanthophylls, but in contrast to AstaP-orange1, induces a pronounced bathochromic shift and a near-UV spectral bump upon binding ketocarotenoids, which is reminiscent of photoactivated Orange Carotenoid Protein (OCP). Mutagenesis and domain-swap experiments indicate that its unique spectral tuning likely results from carotenoid isomerization, forced by the interplay between its N-terminal jaw and body subdomains connected by the hinge loop of different sequence and length. This study attempts to rationalize the spectral and functional diversification of AstaPs and highlights their potential as engineered modules for carotenoid delivery.
{"title":"Crystal structure and functional characterization of the microalgal carotenoprotein AstaP-pink1.","authors":"Yury B Slonimskiy, Daria A Lunegova, Andrey S Nikolaev, Ilya O Matyuta, Konstantin E Klementiev, Vladimir O Popov, Konstantin M Boyko, Ivan Yu Gushchin, Nikolai N Sluchanko","doi":"10.1016/j.bbrc.2026.153374","DOIUrl":"https://doi.org/10.1016/j.bbrc.2026.153374","url":null,"abstract":"<p><p>The recently discovered family of microalgal water-soluble astaxanthin-binding proteins (AstaPs) functions in carotenoid sequestration and transfer. We present the crystal structure and characterization of AstaP-pink1, a homolog from Scenedesmus sp. We show that despite low sequence identity with the known AstaP-orange1, AstaP-pink1 also binds various xanthophylls, but in contrast to AstaP-orange1, induces a pronounced bathochromic shift and a near-UV spectral bump upon binding ketocarotenoids, which is reminiscent of photoactivated Orange Carotenoid Protein (OCP). Mutagenesis and domain-swap experiments indicate that its unique spectral tuning likely results from carotenoid isomerization, forced by the interplay between its N-terminal jaw and body subdomains connected by the hinge loop of different sequence and length. This study attempts to rationalize the spectral and functional diversification of AstaPs and highlights their potential as engineered modules for carotenoid delivery.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"805 ","pages":"153374"},"PeriodicalIF":2.2,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117460","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 : 2026-01-28DOI: 10.1016/j.bbrc.2026.153356
Wanyi Luo , Muxin Yu , Chuwei Zheng , Xiaowen Li , Xiaotian Ma , Guocheng Zeng , Jinming Zhang , Xia Ji , Liyan Sun
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic liver condition closely linked to metabolic dysregulation. In its progressive stage, metabolic dysfunction-associated steatohepatitis (MASH), hepatocytes face pathological insults including lipotoxicity and inflammatory cell infiltration. Sustained exposure to these stressors severely disrupts hepatocyte mitochondrial homeostasis, culminating in mitochondrial dysfunction. Crucially, mitochondrial dysfunction is intimately associated with chronic inflammation. After injury, mitochondria produce large amounts of mitochondrial reactive oxygen species (mtROS) or release mitochondrial damage-associated molecules that act as signaling molecules to recruit and activate inflammatory cells, such as neutrophils. Activated neutrophils release neutrophil extracellular traps (NETs), which exacerbate liver inflammation, driving MASH progression towards liver cancer. Despite advances in the understanding of MASLD pathophysiology, challenges remain in identifying relation between mitochondrial dysfunction and intrahepatic inflammation. Intercellular communication, primarily mediated by extracellular vesicles (EVs), plays a pivotal role in this pathology. EVs transport diverse bioactive cargo from donor to recipient cells, modulating various pathophysiological processes. This review synthesizes current literature on mitochondrial dysfunction and chronic inflammation in MASH/MASLD, examines the critical role of intrahepatic intercellular communication, particularly via EVs, and highlights targeting mitochondria as a promising therapeutic strategy for MASH.
{"title":"Mitochondrial dysfunction in MASH: Focusing on chronic inflammation and intercellular communication","authors":"Wanyi Luo , Muxin Yu , Chuwei Zheng , Xiaowen Li , Xiaotian Ma , Guocheng Zeng , Jinming Zhang , Xia Ji , Liyan Sun","doi":"10.1016/j.bbrc.2026.153356","DOIUrl":"10.1016/j.bbrc.2026.153356","url":null,"abstract":"<div><div>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic liver condition closely linked to metabolic dysregulation. In its progressive stage, metabolic dysfunction-associated steatohepatitis (MASH), hepatocytes face pathological insults including lipotoxicity and inflammatory cell infiltration. Sustained exposure to these stressors severely disrupts hepatocyte mitochondrial homeostasis, culminating in mitochondrial dysfunction. Crucially, mitochondrial dysfunction is intimately associated with chronic inflammation. After injury, mitochondria produce large amounts of mitochondrial reactive oxygen species (mtROS) or release mitochondrial damage-associated molecules that act as signaling molecules to recruit and activate inflammatory cells, such as neutrophils. Activated neutrophils release neutrophil extracellular traps (NETs), which exacerbate liver inflammation, driving MASH progression towards liver cancer. Despite advances in the understanding of MASLD pathophysiology, challenges remain in identifying relation between mitochondrial dysfunction and intrahepatic inflammation. Intercellular communication, primarily mediated by extracellular vesicles (EVs), plays a pivotal role in this pathology. EVs transport diverse bioactive cargo from donor to recipient cells, modulating various pathophysiological processes. This review synthesizes current literature on mitochondrial dysfunction and chronic inflammation in MASH/MASLD, examines the critical role of intrahepatic intercellular communication, particularly via EVs, and highlights targeting mitochondria as a promising therapeutic strategy for MASH.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"804 ","pages":"Article 153356"},"PeriodicalIF":2.2,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146076943","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 : 2026-01-28DOI: 10.1016/j.bbrc.2026.153369
Fan Yang , Jiayi Su , Yaru Li , Jieyu Zhao , Eoin C. Whelan , Wenhua Xu , Guanghua Li , Tingting Ge , Lu Yuan , Haoyu Liu , Changmin Niu , Luping Yu , Ying Zheng
Stomatin-like protein 2 (STOML2) localizes to the mitochondrial inner membrane and regulates mitochondrial biogenesis and function. STOML2's role in spermatogenesis is unknown but given that proper mitochondrial function is required proper male germ cell development and function, we elected to study STOML2's role in the testis. The expression pattern of STOML2 in mouse testes was investigated by RT-PCR and Western blot. Stoml2 RNA was highly expressed in mouse testes and STOML2 protein was localized in the cytoplasm of testicular germ cells. A Stoml2 knockout (KO) mouse model was generated and phenotypes were assessed. Stoml2 KO male mice displayed normal morphology and weight of testes and epididymides, as well as normal fertility. The number and morphology of sperm from Stoml2 KO mice were not changed significantly. Histological analyses of KO testes revealed normal spermatogenesis, and the number of testicular germ cells and Sertoli cells were not significantly altered. Taken together, our results demonstrate that STOML2 is not required for spermatogenesis and male fertility in mice.
{"title":"STOML2 is not essential for spermatogenesis and male fertility in mice","authors":"Fan Yang , Jiayi Su , Yaru Li , Jieyu Zhao , Eoin C. Whelan , Wenhua Xu , Guanghua Li , Tingting Ge , Lu Yuan , Haoyu Liu , Changmin Niu , Luping Yu , Ying Zheng","doi":"10.1016/j.bbrc.2026.153369","DOIUrl":"10.1016/j.bbrc.2026.153369","url":null,"abstract":"<div><div>Stomatin-like protein 2 (STOML2) localizes to the mitochondrial inner membrane and regulates mitochondrial biogenesis and function. STOML2's role in spermatogenesis is unknown but given that proper mitochondrial function is required proper male germ cell development and function, we elected to study STOML2's role in the testis. The expression pattern of STOML2 in mouse testes was investigated by RT-PCR and Western blot. <em>Stoml2</em> RNA was highly expressed in mouse testes and STOML2 protein was localized in the cytoplasm of testicular germ cells. A <em>Stoml2</em> knockout (KO) mouse model was generated and phenotypes were assessed. <em>Stoml2</em> KO male mice displayed normal morphology and weight of testes and epididymides, as well as normal fertility. The number and morphology of sperm from <em>Stoml2</em> KO mice were not changed significantly. Histological analyses of KO testes revealed normal spermatogenesis, and the number of testicular germ cells and Sertoli cells were not significantly altered. Taken together, our results demonstrate that STOML2 is not required for spermatogenesis and male fertility in mice.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"804 ","pages":"Article 153369"},"PeriodicalIF":2.2,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146071118","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 : 2026-01-28DOI: 10.1016/j.bbrc.2026.153370
Kamila Szumska, Fatmanur Sabir, Monika Szeliga
Glioblastoma (GBM) is the most malignant primary brain tumor. To adapt to intrinsic oxidative stress, GBM cells upregulate antioxidant systems. Out of six peroxiredoxins (PRDX) involved in protecting cells from oxidative stress, PRDX1 and PRDX4 are proteins that have been attributed with GBM-promoting properties. The role of PRDX2 in these tumors remains elusive. We have recently reported that treatment with conoidin A (CONA), considered a covalent inhibitor of PRDX2, diminished growth of GBM cells. The question arose whether PRDX2 itself affects the growth of GBM cells and whether the decrease in survival observed under CONA treatment could be due to inhibition of PRDX2 activity. To address this issue, we silenced PRDX2 in human GBM cells, U87MG and LN229, which reduced cell viability to a degree similar to that observed in PRDX4-deficient GBM cells used here as an acknowledged reference. Additionally, PRDX2 silencing inhibited growth of U87MG cells and increased the level of reactive oxygen species. Furthermore, such modulation reduced susceptibility to CONA, suggesting that this compound exerts its effect on cell viability at least partially through PRDX2 inhibition.
胶质母细胞瘤（GBM）是恶性程度最高的原发性脑肿瘤。为了适应内在的氧化应激，GBM细胞上调抗氧化系统。在参与保护细胞免受氧化应激的六种过氧化物还毒素（PRDX）中，PRDX1和PRDX4是被认为具有促进gbm特性的蛋白质。PRDX2在这些肿瘤中的作用尚不清楚。我们最近报道了conoidin A （CONA）的治疗，被认为是PRDX2的共价抑制剂，可以减少GBM细胞的生长。问题是PRDX2本身是否会影响GBM细胞的生长，以及CONA治疗下观察到的存活率下降是否可能是由于PRDX2活性的抑制。为了解决这个问题，我们在人GBM细胞、U87MG和LN229中沉默了PRDX2，这在一定程度上降低了细胞活力，类似于在prdx4缺陷的GBM细胞中观察到的，这里作为公认的参考。此外，PRDX2沉默抑制了U87MG细胞的生长，增加了活性氧的水平。此外，这种调节降低了对CONA的敏感性，表明该化合物至少部分通过抑制PRDX2来影响细胞活力。
{"title":"Peroxiredoxin 2 contributes to the malignant phenotype of glioblastoma cells","authors":"Kamila Szumska, Fatmanur Sabir, Monika Szeliga","doi":"10.1016/j.bbrc.2026.153370","DOIUrl":"10.1016/j.bbrc.2026.153370","url":null,"abstract":"<div><div>Glioblastoma (GBM) is the most malignant primary brain tumor. To adapt to intrinsic oxidative stress, GBM cells upregulate antioxidant systems. Out of six peroxiredoxins (PRDX) involved in protecting cells from oxidative stress, PRDX1 and PRDX4 are proteins that have been attributed with GBM-promoting properties. The role of PRDX2 in these tumors remains elusive. We have recently reported that treatment with conoidin A (CONA), considered a covalent inhibitor of PRDX2, diminished growth of GBM cells. The question arose whether PRDX2 itself affects the growth of GBM cells and whether the decrease in survival observed under CONA treatment could be due to inhibition of PRDX2 activity. To address this issue, we silenced <em>PRDX2</em> in human GBM cells, U87MG and LN229, which reduced cell viability to a degree similar to that observed in PRDX4-deficient GBM cells used here as an acknowledged reference. Additionally, <em>PRDX2</em> silencing inhibited growth of U87MG cells and increased the level of reactive oxygen species. Furthermore, such modulation reduced susceptibility to CONA, suggesting that this compound exerts its effect on cell viability at least partially through PRDX2 inhibition.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"804 ","pages":"Article 153370"},"PeriodicalIF":2.2,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146077010","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 : 2026-01-27DOI: 10.1016/j.bbrc.2026.153353
Chaoyan Fan, Min Peng, Wuguang Zhang
Purpose
Ovarian cancer remains the deadliest gynecologic malignancy. Erianin, a plant-derived compound with antitumor activity through inducing ferroptosis—an iron-dependent programmed cell death that has been shown in other contexts to enhance tumor sensitivity to chemotherapy—has not yet been fully explored in ovarian cancer. We therefore evaluated its anti-proliferative effects and underlying mechanism.
Methods
Cell viability (CCK-8), cell death (Annexin V-FITC/PI flow cytometry, Western blot), and lipid peroxidation assays were performed in A2780 and ES-2 cells. Transcriptome (RNA-seq) and GO enrichment analyses identified signaling pathways, followed by mechanistic validation. Antitumor efficacy was verified in a nude-mouse xenograft model.
Results
Erianin exhibited a dose-dependent inhibitory effect on the proliferation of ovarian cancer cells A2780 and ES-2. Ferroptosis was identified as the primary mode of cell death, supported by a combination of evidence: (i) preferential rescue with the ferroptosis inhibitor Ferrostatin-1; (ii) characteristic molecular changes, including downregulation of key suppressors (GPX4, FTH1, SLC7A11) and upregulation of the pro-ferroptotic protein ACSL4; and (iii) elevated lipid peroxidation (MDA) and ROS alongside depleted GSH. Annexin V-FITC/PI flow cytometry was used to assess overall cell death patterns. Mechanistic studies showed that Erianin promoted ferroptosis via activation of the JNK signaling pathway and upregulation of PDP2 expression. In vivo, Erianin significantly suppressed tumor growth and induced molecular changes indicative of a less aggressive phenotype, including modulation of epithelial-mesenchymal transition (EMT) markers (increased E-cadherin, decreased N-cadherin).
Conclusion
Erianin induces ferroptosis via PDP2-mediated activation of the JNK signaling pathway, thereby restraining ovarian cancer growth in vitro and in vivo. These findings provide a mechanistic rationale for further evaluation of Erianin as a ferroptosis-inducing therapeutic candidate, including in chemoresistant settings.
{"title":"Erianin induces ferroptosis in ovarian cancer cells by upregulating PDP2 and activating the JNK signaling pathway","authors":"Chaoyan Fan, Min Peng, Wuguang Zhang","doi":"10.1016/j.bbrc.2026.153353","DOIUrl":"10.1016/j.bbrc.2026.153353","url":null,"abstract":"<div><h3>Purpose</h3><div>Ovarian cancer remains the deadliest gynecologic malignancy. Erianin, a plant-derived compound with antitumor activity through inducing ferroptosis—an iron-dependent programmed cell death that has been shown in other contexts to enhance tumor sensitivity to chemotherapy—has not yet been fully explored in ovarian cancer. We therefore evaluated its anti-proliferative effects and underlying mechanism.</div></div><div><h3>Methods</h3><div>Cell viability (CCK-8), cell death (Annexin V-FITC/PI flow cytometry, Western blot), and lipid peroxidation assays were performed in A2780 and ES-2 cells. Transcriptome (RNA-seq) and GO enrichment analyses identified signaling pathways, followed by mechanistic validation. Antitumor efficacy was verified in a nude-mouse xenograft model.</div></div><div><h3>Results</h3><div>Erianin exhibited a dose-dependent inhibitory effect on the proliferation of ovarian cancer cells A2780 and ES-2. Ferroptosis was identified as the primary mode of cell death, supported by a combination of evidence: (i) preferential rescue with the ferroptosis inhibitor Ferrostatin-1; (ii) characteristic molecular changes, including downregulation of key suppressors (GPX4, FTH1, SLC7A11) and upregulation of the pro-ferroptotic protein ACSL4; and (iii) elevated lipid peroxidation (MDA) and ROS alongside depleted GSH. Annexin V-FITC/PI flow cytometry was used to assess overall cell death patterns. Mechanistic studies showed that Erianin promoted ferroptosis via activation of the JNK signaling pathway and upregulation of PDP2 expression. In vivo, Erianin significantly suppressed tumor growth and induced molecular changes indicative of a less aggressive phenotype, including modulation of epithelial-mesenchymal transition (EMT) markers (increased E-cadherin, decreased N-cadherin).</div></div><div><h3>Conclusion</h3><div>Erianin induces ferroptosis via PDP2-mediated activation of the JNK signaling pathway, thereby restraining ovarian cancer growth in vitro and in vivo. These findings provide a mechanistic rationale for further evaluation of Erianin as a ferroptosis-inducing therapeutic candidate, including in chemoresistant settings.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"804 ","pages":"Article 153353"},"PeriodicalIF":2.2,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146077011","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 : 2026-01-27DOI: 10.1016/j.bbrc.2026.153355
Sebastian Vogel, Sayuri Kamimura, Eric Nguyen, Meghann Smith, Luis E F Almeida, Patricia Zerfas, Kapil Bharti, Christian Combs, Michelly Sampaio de Melo, Zenaide M N Quezado
The platelet nucleotide-binding domain leucine-rich repeat-containing protein 3 (NLRP3) inflammasome is upregulated in sickle cell disease (SCD) and promotes platelet aggregation. We previously identified Bruton tyrosine kinase (BTK) as a critical regulator of the platelet NLRP3 inflammasome. However, whether NLRP3 contributes to platelet function beyond aggregation in SCD and whether these effects can be modulated through BTK inhibition, has been incompletely understood. Here, we show that platelet secretion, platelet spreading, platelet aggregation, and in vitro thrombus formation in response to collagen are elevated in SCD mice and are reduced following treatment of mice with the NLRP3 inhibitor MCC950 or the BTK inhibitor ibrutinib. The NLRP3 activator nigericin partially reversed the inhibitory effects of ibrutinib across all platelet function assays. Together, we identify the NLRP3 inflammasome as a critical mediator of platelet hyperreactivity in SCD mice, which can be targeted via BTK inhibition.
{"title":"NLRP3 inflammasome-mediated platelet hyperreactivity in sickle cell mice is targetable by BTK inhibition.","authors":"Sebastian Vogel, Sayuri Kamimura, Eric Nguyen, Meghann Smith, Luis E F Almeida, Patricia Zerfas, Kapil Bharti, Christian Combs, Michelly Sampaio de Melo, Zenaide M N Quezado","doi":"10.1016/j.bbrc.2026.153355","DOIUrl":"https://doi.org/10.1016/j.bbrc.2026.153355","url":null,"abstract":"<p><p>The platelet nucleotide-binding domain leucine-rich repeat-containing protein 3 (NLRP3) inflammasome is upregulated in sickle cell disease (SCD) and promotes platelet aggregation. We previously identified Bruton tyrosine kinase (BTK) as a critical regulator of the platelet NLRP3 inflammasome. However, whether NLRP3 contributes to platelet function beyond aggregation in SCD and whether these effects can be modulated through BTK inhibition, has been incompletely understood. Here, we show that platelet secretion, platelet spreading, platelet aggregation, and in vitro thrombus formation in response to collagen are elevated in SCD mice and are reduced following treatment of mice with the NLRP3 inhibitor MCC950 or the BTK inhibitor ibrutinib. The NLRP3 activator nigericin partially reversed the inhibitory effects of ibrutinib across all platelet function assays. Together, we identify the NLRP3 inflammasome as a critical mediator of platelet hyperreactivity in SCD mice, which can be targeted via BTK inhibition.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"805 ","pages":"153355"},"PeriodicalIF":2.2,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146123569","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 : 2026-01-27DOI: 10.1016/j.bbrc.2026.153357
Chae Yeong Lee , Woo Cheol Lee , Kyusung Chae , Eunhee Kim , Eunha Hwang , Yangmee Kim
Adenylate kinase (Adk) is essential for cellular energy homeostasis as it catalyzes the reversible transfer of γ-phosphate from ATP to AMP. In most long-variants, such as Escherichia coli Adk, large-scale domain motions, concerted movements of the AMP-binding domain (AMPbd) and ATP-lid, are essential for catalytic efficiency. However, the structural diversity observed in Adk variants, especially the short-variant Adk from Mycobacterium tuberculosis (MtAdk) featuring a truncated ATP-lid, raises questions regarding the adaptation of its dynamic regulation and functional mechanisms to support survival in resource-limited and hostile environments. Here, using 15N-chemical exchange saturation transfer experiments, we identified key glycine residues, G32 and G46 in AMPbd and G128 within the ATP-lid, that undergo slow conformational exchange on the millisecond timescale. Glycine substitutions with proline revealed their critical roles: G32P and G128P mutations significantly impaired catalytic turnover, whereas G46P exerted a moderate effect. Molecular dynamics simulations revealed that these substitutions restrict local flexibility; G32P and G128P lock the enzyme in an open, less active conformation, whereas G46P destabilizes the hinge region, thereby hindering proper domain closure. Our integrated approach reveals that these glycine-mediated flexibilities are essential for substrate recognition and catalysis in MtAdk. These findings highlight the fundamental mechanistic divergence between short- and long-variant Adks, emphasizing glycine-mediated conformational plasticity as key in enzyme regulation, with promising implications in targeted therapies against bacterial survival strategies.
{"title":"NMR-driven insights into the evolutionary adaptation and dynamic regulation of Mycobacterium tuberculosis adenylate kinase: The critical role of glycine-mediated flexibility","authors":"Chae Yeong Lee , Woo Cheol Lee , Kyusung Chae , Eunhee Kim , Eunha Hwang , Yangmee Kim","doi":"10.1016/j.bbrc.2026.153357","DOIUrl":"10.1016/j.bbrc.2026.153357","url":null,"abstract":"<div><div>Adenylate kinase (Adk) is essential for cellular energy homeostasis as it catalyzes the reversible transfer of γ-phosphate from ATP to AMP. In most long-variants, such as <em>Escherichia coli</em> Adk, large-scale domain motions, concerted movements of the AMP-binding domain (AMPbd) and ATP-lid, are essential for catalytic efficiency. However, the structural diversity observed in Adk variants, especially the short-variant Adk from <em>Mycobacterium tuberculosis</em> (MtAdk) featuring a truncated ATP-lid, raises questions regarding the adaptation of its dynamic regulation and functional mechanisms to support survival in resource-limited and hostile environments. Here, using <sup>15</sup>N-chemical exchange saturation transfer experiments, we identified key glycine residues, G32 and G46 in AMPbd and G128 within the ATP-lid, that undergo slow conformational exchange on the millisecond timescale. Glycine substitutions with proline revealed their critical roles: G32P and G128P mutations significantly impaired catalytic turnover, whereas G46P exerted a moderate effect. Molecular dynamics simulations revealed that these substitutions restrict local flexibility; G32P and G128P lock the enzyme in an open, less active conformation, whereas G46P destabilizes the hinge region, thereby hindering proper domain closure. Our integrated approach reveals that these glycine-mediated flexibilities are essential for substrate recognition and catalysis in MtAdk. These findings highlight the fundamental mechanistic divergence between short- and long-variant Adks, emphasizing glycine-mediated conformational plasticity as key in enzyme regulation, with promising implications in targeted therapies against bacterial survival strategies.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"804 ","pages":"Article 153357"},"PeriodicalIF":2.2,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146077008","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}
The complex and heterogeneous molecular mechanisms of asthma are currently unclear, and treatment outcomes are dismal in some patients. This study aimed to identify biomarkers with diagnostic and therapeutic potential.
Methods
Gene Expression Omnibus was used to obtain asthma-related gene expression data for identifying differentially expressed genes. They were subjected to functional and pathway enrichment analyses using the Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Disease Ontology. Gene Set Enrichment Analysis and Gene Set Variation Analysis were used to explore potential asthma-related mechanisms. Candidate biomarkers were identified using two machine learning algorithms and evaluated via ROC curve analysis. Immune cell fractions were assessed using CIBERSORT, and biomarker expression was validated in external database, in vivo, and in vitro studies.
Results
The 168 differentially expressed genes (96 upregulated and 72 downregulated) were enriched for xenobiotic stimuli, glutathione transferase activity, negative regulation of proteolysis, and endopeptidase inhibitor activity; the pathways for glutathione metabolism, xenobiotic metabolism via cytochrome P450, and chemical carcinogenesis involving DNA adducts; and for periodontitis and asthma. WNK4 and FKBP5 were identified as critical genes and were validated using ROC assays. Correlations were found between WNK4 and M2-macrophages, and between FKBP5 expression and mast cells, resting NK cells, and T cells. Our findings demonstrated increased FKBP5 expression and decreased WNK4 expression in the asthmatic cohort, aligning with the results from dataset analyses. This concordance reinforces the reliability and validity of the bioinformatics assessments.
Conclusions
This study identified WNK4 and FKBP5 as candidate biomarkers of asthma warranting further clinical validation, thus contributing to a deeper understanding of asthma pathogenesis and offering a theoretical basis for future treatment strategies.
{"title":"Role of WNK4 and FKBP5 in asthma: Insights from bioinformatics analysis, machine learning, and preliminary validation","authors":"Meng Liu, Yue Li, Tianci Jiang, Lingling Dai, Zhe Cheng","doi":"10.1016/j.bbrc.2026.153351","DOIUrl":"10.1016/j.bbrc.2026.153351","url":null,"abstract":"<div><h3>Background</h3><div>The complex and heterogeneous molecular mechanisms of asthma are currently unclear, and treatment outcomes are dismal in some patients. This study aimed to identify biomarkers with diagnostic and therapeutic potential.</div></div><div><h3>Methods</h3><div>Gene Expression Omnibus was used to obtain asthma-related gene expression data for identifying differentially expressed genes. They were subjected to functional and pathway enrichment analyses using the Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Disease Ontology. Gene Set Enrichment Analysis and Gene Set Variation Analysis were used to explore potential asthma-related mechanisms. Candidate biomarkers were identified using two machine learning algorithms and evaluated via ROC curve analysis. Immune cell fractions were assessed using CIBERSORT, and biomarker expression was validated in external database, in vivo, and in vitro studies.</div></div><div><h3>Results</h3><div>The 168 differentially expressed genes (96 upregulated and 72 downregulated) were enriched for xenobiotic stimuli, glutathione transferase activity, negative regulation of proteolysis, and endopeptidase inhibitor activity; the pathways for glutathione metabolism, xenobiotic metabolism via cytochrome P450, and chemical carcinogenesis involving DNA adducts; and for periodontitis and asthma. WNK4 and FKBP5 were identified as critical genes and were validated using ROC assays. Correlations were found between WNK4 and M2-macrophages, and between FKBP5 expression and mast cells, resting NK cells, and T cells. Our findings demonstrated increased FKBP5 expression and decreased WNK4 expression in the asthmatic cohort, aligning with the results from dataset analyses. This concordance reinforces the reliability and validity of the bioinformatics assessments.</div></div><div><h3>Conclusions</h3><div>This study identified WNK4 and FKBP5 as candidate biomarkers of asthma warranting further clinical validation, thus contributing to a deeper understanding of asthma pathogenesis and offering a theoretical basis for future treatment strategies.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"803 ","pages":"Article 153351"},"PeriodicalIF":2.2,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146076710","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 : 2026-01-27DOI: 10.1016/j.bbrc.2026.153358
Jiru Hou, Jiaxuan Li, Chong Zhao, Shutao Yin, Hongbo Hu
Fructose is an abundant monosaccharide in the human diet and an important source of energy in the human body. GLUT5, a member of facilitative glucose transporter family, is the only membrane transporter that specifically transports fructose in the human body, and plays an important role in dietary fructose uptake and metabolism. Previous studies have shown that medium-chain fatty acids (MCFAs) can regulate glucose metabolism via modulating glucose transporters. However, it has not been addressed if MCFAs can regulate GLUT5-mediated fructose metabolism. In the present study, we demonstrated for the first time that MCFAs but not short chain or long chain fatty acids are able to promote fructose uptake in both IEC-18 rat intestinal epithelial cells and human MDA-MB-231 breast cancer cells (a commonly used cell line for fructose metabolism-related study) measured by 1-NBD-Fructose-based assay, which are well correlated with the activation of GLUT5-KHK axis. Moreover, the activation of GLUT5-ketohexokinase (KHK) axis was also achieved in vivo by the treatment with tricapylin, a precursor of octanoic acid (OA), leading to the improvement in fructose-based energy recovery after fasting. The findings of the present study not only provide novel mechanistic support for MCFAs as regulator of carbohydrate metabolism, but also denote that MCFAs could be useable for managing fructose-associated metabolic diseases or as an enhancer for energy recovery after fasting or exercise.
{"title":"Medium-chain fatty acids activate fructose metabolism via up-regulating GLUT5-KHK axis","authors":"Jiru Hou, Jiaxuan Li, Chong Zhao, Shutao Yin, Hongbo Hu","doi":"10.1016/j.bbrc.2026.153358","DOIUrl":"10.1016/j.bbrc.2026.153358","url":null,"abstract":"<div><div>Fructose is an abundant monosaccharide in the human diet and an important source of energy in the human body. GLUT5, a member of facilitative glucose transporter family, is the only membrane transporter that specifically transports fructose in the human body, and plays an important role in dietary fructose uptake and metabolism. Previous studies have shown that medium-chain fatty acids (MCFAs) can regulate glucose metabolism via modulating glucose transporters. However, it has not been addressed if MCFAs can regulate GLUT5-mediated fructose metabolism. In the present study, we demonstrated for the first time that MCFAs but not short chain or long chain fatty acids are able to promote fructose uptake in both IEC-18 rat intestinal epithelial cells and human MDA-MB-231 breast cancer cells (a commonly used cell line for fructose metabolism-related study) measured by 1-NBD-Fructose-based assay, which are well correlated with the activation of GLUT5-KHK axis. Moreover, the activation of GLUT5-ketohexokinase (KHK) axis was also achieved in vivo by the treatment with tricapylin, a precursor of octanoic acid (OA), leading to the improvement in fructose-based energy recovery after fasting. The findings of the present study not only provide novel mechanistic support for MCFAs as regulator of carbohydrate metabolism, but also denote that MCFAs could be useable for managing fructose-associated metabolic diseases or as an enhancer for energy recovery after fasting or exercise.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"804 ","pages":"Article 153358"},"PeriodicalIF":2.2,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146071117","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 : 2026-01-26DOI: 10.1016/j.bbrc.2026.153354
Jiayi Yang , Xiaoyan Pan , Xiaoyan Luo , Xueting Zheng , Jiali Wang
Renal cell carcinoma (RCC), the most common type of urogenital cancer, accounts for about 80 % of malignant renal tumors. Clear cell renal cell carcinoma (ccRCC), composed of cells filled with lipid droplets in cytoplasm, is the most common subtype of RCC. Mechanisms underlying ccRCC progression and metastasis are complicated and remain far from being clarified. Mitochondria, which serve as cellular energy supplier and central signal hubs, are involved in various physiological and pathological processes. Mounting evidence has revealed that mitochondrial changes, such as mutations, abnormal mitophagy and metabolisms and excessive reactive oxide species (ROS) are closely related with the progression, prognosis, metastasis and drug resistance of RCC and ccRCC. In this review, we'll provide an overview on mitochondrial changes in RCC, especially in ccRCC, and discuss their possible roles in the tumorigenesis and prognosis as well as their potential in serving as biomarkers and therapeutic targets.
{"title":"Mitochondrial changes in clear cell renal cell carcinoma: mechanisms and potential targets","authors":"Jiayi Yang , Xiaoyan Pan , Xiaoyan Luo , Xueting Zheng , Jiali Wang","doi":"10.1016/j.bbrc.2026.153354","DOIUrl":"10.1016/j.bbrc.2026.153354","url":null,"abstract":"<div><div>Renal cell carcinoma (RCC), the most common type of urogenital cancer, accounts for about 80 % of malignant renal tumors. Clear cell renal cell carcinoma (ccRCC), composed of cells filled with lipid droplets in cytoplasm, is the most common subtype of RCC. Mechanisms underlying ccRCC progression and metastasis are complicated and remain far from being clarified. Mitochondria, which serve as cellular energy supplier and central signal hubs, are involved in various physiological and pathological processes. Mounting evidence has revealed that mitochondrial changes, such as mutations, abnormal mitophagy and metabolisms and excessive reactive oxide species (ROS) are closely related with the progression, prognosis, metastasis and drug resistance of RCC and ccRCC. In this review, we'll provide an overview on mitochondrial changes in RCC, especially in ccRCC, and discuss their possible roles in the tumorigenesis and prognosis as well as their potential in serving as biomarkers and therapeutic targets.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"804 ","pages":"Article 153354"},"PeriodicalIF":2.2,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146077013","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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