Biochemistry and Biophysics Reports最新文献_第3页

Exploratory comparison of PASC and SARS-CoV-2 infection through metabolomics and lipidomics in early pandemic and Omicron-era 利用代谢组学和脂质组学对PASC和SARS-CoV-2感染在大流行早期和ommicron时代的探索性比较

IF 2.2

Biochemistry and Biophysics Reports Pub Date : 2026-06-01 Epub Date: 2026-05-30 DOI: 10.1016/j.bbrep.2026.102652

Chelsea M. Rock , Laura M. Johnson , Adrianna L. Westbrook , Richard Parsons , John D. Roback , Gregory L. Damhorst , Wilbur A. Lam , Greg S. Martin , Madelyn C. Houser , Jennifer K. Frediani

{"title":"Exploratory comparison of PASC and SARS-CoV-2 infection through metabolomics and lipidomics in early pandemic and Omicron-era","authors":"Chelsea M. Rock , Laura M. Johnson , Adrianna L. Westbrook , Richard Parsons , John D. Roback , Gregory L. Damhorst , Wilbur A. Lam , Greg S. Martin , Madelyn C. Houser , Jennifer K. Frediani","doi":"10.1016/j.bbrep.2026.102652","DOIUrl":"10.1016/j.bbrep.2026.102652","url":null,"abstract":"<div><div>While symptomology of post-acute sequelae of COVID-19 (PASC) is well-known, and more risk factors are being identified, the physiological mechanisms of this condition remain largely undetermined. In the early pandemic into the pre-Omicron era, plasma samples were obtained from SARS-CoV-2 positive patients admitted to the hospital or in the emergency department at a single timepoint. The 68 convenience samples were analyzed using metabolomics and lipidomics to identify any signatures associated with development of PASC. After correction for false discovery rate, no metabolomic features distinguished the 24% of patients that developed PASC from those who did not. Glycerophospholipids, including PI(20:4_18:0), and triglycerides, which are known to be involved in energy metabolism and immune responses, differed in abundance in PASC compared to non-PASC patients. A small sample size, batch effects, and inaccessible clinical data resulted in an exploratory analysis with moderate effects in this convenience sample. Discerning biological pathways in SARS-CoV-2 infection, PASC, and their linkage may help elucidate causes and uncover preventative and treatment approaches for patients with PASC.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"46 ","pages":"Article 102652"},"PeriodicalIF":2.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148167379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Persistent prostaglandin E2 upregulation and hormonal multi-resistance: A hypothesis for long COVID 前列腺素E2持续上调和激素多重耐药：长期COVID的假设

IF 2.2

Biochemistry and Biophysics Reports Pub Date : 2026-06-01 Epub Date: 2026-03-10 DOI: 10.1016/j.bbrep.2026.102518

Vjera Ramer , Gert A. van Montfrans

{"title":"Persistent prostaglandin E2 upregulation and hormonal multi-resistance: A hypothesis for long COVID","authors":"Vjera Ramer , Gert A. van Montfrans","doi":"10.1016/j.bbrep.2026.102518","DOIUrl":"10.1016/j.bbrep.2026.102518","url":null,"abstract":"<div><div>An explanation for long COVID (LC) and its many symptoms remains elusive, and no unifying upstream mediator of its pathophysiology has yet been identified. Viral infections, including COVID-19, upregulate Prostaglandin E2 (PGE2), - the principal lipid mediator of inflammation. PGE2 has broad paracrine effects, including modulation of autoantibodies, nervous systems, blood pressure, glucose levels, and apoptosis. Upregulated, PGE2 may drive multiple pathological processes through its four receptors: EP1-EP4. Through EP3, PGE2 stimulates characteristic viral sickness symptoms. Both severe and mild disease may precede LC, possibly reflecting either excessive or insufficient EP3 activity, which we term “EP3 up” and “EP3 down”, respectively. In individuals with “EP3 up” or “EP3 down” states, elevated PGE2 levels may disrupt homeostasis. Diverse physical and mental stressors upregulate PGE2. Data suggest that multiple hormones and agents stimulate PGE2 production, while PGE2 reportedly antagonizes these agents, possibly functioning as a homeostatic limiter. Sufficiently elevated PGE2, “PGE2 dominance”, may interfere with their activity through inhibiting their release, overlapping subcellular signaling pathways or by stimulating phosphorylation and autoantibodies. Homeostatic elevations of PGE2-stimulating hormones, together with other PGE2-raising factors, may promote resistance to these hormones, resulting in persistent PGE2 upregulation. Literature suggests that PGE2 overactivity, mediated by imbalanced EP receptor signaling, aligns with the diverse symptomatology of LC. Based on our literature analysis, we propose that persistent upregulation of PGE2 plays a pivotal role in the development of LC. Consequently, validation of elements of this framework may help guide exploration of therapeutic strategies targeting PGE2 pathways or EP receptor regulation.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"46 ","pages":"Article 102518"},"PeriodicalIF":2.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147388235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Role of Dlk1–Notch signaling in impaired neurogenesis and cognitive decline in chronic cerebral hypoperfusion Dlk1-Notch信号在慢性脑灌注不足患者神经发生受损和认知能力下降中的作用

IF 2.2

Biochemistry and Biophysics Reports Pub Date : 2026-06-01 Epub Date: 2026-05-28 DOI: 10.1016/j.bbrep.2026.102650

Yoshiyuki Moriyama, Rena Hasegawa, Hikaru Endo, Sayaka Matsumura, Ryotaro Kaneko, Hideki Hayashi, Yui Iwatani, Norio Takagi

{"title":"Role of Dlk1–Notch signaling in impaired neurogenesis and cognitive decline in chronic cerebral hypoperfusion","authors":"Yoshiyuki Moriyama, Rena Hasegawa, Hikaru Endo, Sayaka Matsumura, Ryotaro Kaneko, Hideki Hayashi, Yui Iwatani, Norio Takagi","doi":"10.1016/j.bbrep.2026.102650","DOIUrl":"10.1016/j.bbrep.2026.102650","url":null,"abstract":"<div><div>Vascular dementia (VaD) is characterized by chronic cerebral hypoperfusion, leading to cognitive decline. Impaired hippocampal neurogenesis is a crucial pathological feature of VaD. Delta-like 1 homolog (Dlk1)-Notch signaling may contribute to neural stem cell regulation, but the involvement of Dlk1-Notch signaling in impaired hippocampal neurogenesis during hypoperfusion is unclear. Here, we investigated the role of Dlk1 and Notch signaling in a mouse model of chronic cerebral hypoperfusion induced by bilateral carotid artery stenosis (BCAS). We found that BCAS increased Dlk1 levels in hippocampal tissue and cerebrospinal fluid, accompanied by elevated Notch intracellular domain (NICD) expression and reduced doublecortin (Dcx)-positive hippocampal cells. These changes were associated with impaired novel object recognition. In Neuro2a cells, hypoxia-mimetic treatment elevated NICD and extracellular Dlk1 and reduced cell viability, while pharmacological inhibition of Notch signaling partially rescued cell loss and attenuated these changes. These findings suggest that Dlk1-associated Notch activation correlates with impaired hippocampal neurogenesis and memory dysfunction under chronic hypoperfusion. Our results highlight a potential link between altered niche signaling and cognitive decline in VaD, providing a basis for further mechanistic investigation.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"46 ","pages":"Article 102650"},"PeriodicalIF":2.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148167380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Quercetin alleviates CCl4-induced liver fibrosis via regulating gut microbiota and the AGE-RAGE/PI3K/Akt signaling axis 槲皮素通过调节肠道微生物群和AGE-RAGE/PI3K/Akt信号轴减轻ccl4诱导的肝纤维化

IF 2.2

Biochemistry and Biophysics Reports Pub Date : 2026-06-01 Epub Date: 2026-03-09 DOI: 10.1016/j.bbrep.2026.102540

Yi Tang , Yu-Han Jiang , Chen-Yang Wu , Guo-Tai Wang , Meng-Lan Li

{"title":"Quercetin alleviates CCl4-induced liver fibrosis via regulating gut microbiota and the AGE-RAGE/PI3K/Akt signaling axis","authors":"Yi Tang , Yu-Han Jiang , Chen-Yang Wu , Guo-Tai Wang , Meng-Lan Li","doi":"10.1016/j.bbrep.2026.102540","DOIUrl":"10.1016/j.bbrep.2026.102540","url":null,"abstract":"<div><div>The absence of clinically effective anti-fibrotic agents for chronic liver disease represents a critical therapeutic gap. Although the flavonoid quercetin exhibits potent experimental anti-fibrotic activity, its full integrative mechanisms—particularly those involving gut-liver axis crosstalk and specific signaling pathways—remain incompletely elucidated. To address this, we employed an integrated methodological approach encompassing network pharmacology, molecular docking, a CCl<sub>4</sub>-induced murine model of liver fibrosis, 16S rRNA sequencing, and molecular validation to delineate quercetin's anti-fibrotic actions. Network analysis identified tumor necrosis factor (TNF), protein kinase B (Akt1), interleukin-6 (IL-6), and the AGE-RAGE/PI3K/Akt signaling axis as core targets and pathways, findings further corroborated by strong molecular binding affinities. In vivo, quercetin administration reversed CCl<sub>4</sub>-induced body weight loss, ameliorated hepatic injury, reduced fibrogenesis markers, and attenuated pathological collagen deposition. Critically, quercetin restructured gut microbiota composition, enhancing α-diversity indices and favorably modulating the Bacteroidetes and Firmicutes ratio. Western blot analysis revealed quercetin's anti-fibrotic mechanism involves a dual inhibitory effect: primarily downregulating hepatic RAGE expression and concurrently suppressing PI3K-Akt pathway phosphorylation. These findings establish that quercetin ameliorates liver fibrosis through synergistic gut microbiota reprogramming and targeted disruption of the pathogenic AGE-RAGE/PI3K/Akt signaling axis, providing a mechanistic foundation for therapeutic development.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"46 ","pages":"Article 102540"},"PeriodicalIF":2.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147388236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The KLF4-inflammatory pathway is associated with paraquat-induced pulmonary injury and early pro-fibrotic responses klf4炎症通路与百草枯诱导的肺损伤和早期促纤维化反应有关。

IF 2.2

Biochemistry and Biophysics Reports Pub Date : 2026-06-01 Epub Date: 2026-05-24 DOI: 10.1016/j.bbrep.2026.102648

Wei Zhang , Sisi Ye , Jiabao Chen , Jingjing Cao , Dongyang Xie , Xiao Jin , Zhefan Xie , Chunlai Fu

{"title":"The KLF4-inflammatory pathway is associated with paraquat-induced pulmonary injury and early pro-fibrotic responses","authors":"Wei Zhang , Sisi Ye , Jiabao Chen , Jingjing Cao , Dongyang Xie , Xiao Jin , Zhefan Xie , Chunlai Fu","doi":"10.1016/j.bbrep.2026.102648","DOIUrl":"10.1016/j.bbrep.2026.102648","url":null,"abstract":"<div><div>Paraquat, a highly toxic herbicide, frequently causes acute poisoning, predominantly inducing pulmonary injury and fibrosis with high mortality, and no specific antidote is available. This study aimed to explore its pathogenesis using a paraquat-induced mouse model. Results showed that paraquat caused dose-dependent body weight changes, pulmonary edema, and pathological damage (alveolar structure destruction, inflammatory cell infiltration), with elevated levels of inflammatory factors (IL-6, TNF-α, IL-1β) in BALF and lung tissues. It also induced pulmonary early pro-fibrotic responses, evidenced by increased collagen deposition and upregulated mesenchymal markers (α-SMA, Vimentin, Collagen I). RNA sequencing revealed KLF4 was significantly downregulated, and differentially expressed genes (DEGs) were enriched in inflammatory pathways. KLF4 negatively correlated with core genes (GSK3B, MLH1, PRKACA, VDAC1, WNT7B) in pathways like Wnt signaling pathway. These findings indicated that paraquat-induced pulmonary injury and early pro-fibrotic responses are associated with KLF4 downregulation and inflammatory pathway activation, identifying KLF4 as a potential therapeutic target for clinical intervention.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"46 ","pages":"Article 102648"},"PeriodicalIF":2.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148148191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural and functional characterization of human kallistatin 人卡利司他汀的结构和功能表征

IF 2.2

Biochemistry and Biophysics Reports Pub Date : 2026-06-01 Epub Date: 2026-06-02 DOI: 10.1016/j.bbrep.2026.102651

Stephanie T.D. Pham , Kristian W. Nielsen , Jonas H. Graversen , Nanna Kristensen , Lasse B. Steffensen , Andrea R. Lundgaard , José L. Martín-Ventura , Peter Højrup , Yaseelan Palarasah

{"title":"Structural and functional characterization of human kallistatin","authors":"Stephanie T.D. Pham , Kristian W. Nielsen , Jonas H. Graversen , Nanna Kristensen , Lasse B. Steffensen , Andrea R. Lundgaard , José L. Martín-Ventura , Peter Højrup , Yaseelan Palarasah","doi":"10.1016/j.bbrep.2026.102651","DOIUrl":"10.1016/j.bbrep.2026.102651","url":null,"abstract":"<div><div>Kallistatin is a serine protease inhibitor (serpin) that specifically inhibits tissue kallikrein, a key enzyme involved in kinin generation and vascular homeostasis. While serpins are known to polymerize under certain conditions, the structural properties of human kallistatin—particularly its glycosylation profile, tissue distribution, and polymerization potential—remain poorly defined.</div><div>In this study, we generated a panel of kallistatin-specific monoclonal antibodies and developed a sensitive sandwich ELISA that enables reliable quantification of kallistatin in both plasma and tissue-conditioned media. The generated antibodies facilitated both quantitative and qualitative analyses, allowing detailed characterization of kallistatin's structural features, glycosylation profile, and localization in vascular tissue from patients with abdominal aortic aneurysm. Using mass-spectrometry, we characterized the glycosylation sites of kallistatin, providing experimental confirmation of the putative glycosylation at Asn 33.</div><div>Biochemical analyses revealed that kallistatin can polymerize and is susceptible to structural rearrangements typical of serpins. Deglycosylation markedly increased polymer formation demonstrating that glycosylation plays a critical stabilizing role in preventing polymerization. Functional assays using a fluorogenic tissue kallikrein substrate showed that polymerized kallistatin loses inhibitory activity, whereas deglycosylated kallistatin retains normal function. This indicates that glycosylation primarily supports structural stability rather than directly modulating inhibitory capacity.</div><div>These findings provide new insights into kallistatin's structural features, including its glycosylation, stability, and polymerization behavior, and establish essential tools for further exploring its physiological and pathological roles.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"46 ","pages":"Article 102651"},"PeriodicalIF":2.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148167378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An integrated biophysical fragment screening approach identifies novel binders of the CD28 immune receptor 一种集成的生物物理片段筛选方法鉴定了CD28免疫受体的新结合物

IF 2.2

Biochemistry and Biophysics Reports Pub Date : 2026-06-01 Epub Date: 2026-03-07 DOI: 10.1016/j.bbrep.2026.102542

Laura Calvo-Barreiro, Hossam Nada, Moustafa T. Gabr

{"title":"An integrated biophysical fragment screening approach identifies novel binders of the CD28 immune receptor","authors":"Laura Calvo-Barreiro, Hossam Nada, Moustafa T. Gabr","doi":"10.1016/j.bbrep.2026.102542","DOIUrl":"10.1016/j.bbrep.2026.102542","url":null,"abstract":"<div><div>CD28 is an essential costimulatory receptor required for full T cell activation and its dysregulation contributes to multiple immune-mediated pathologies. Despite its central immunological role, CD28 remains largely unexplored as a target for small-molecule modulation, primarily due to the shallow and large interface of its ligand-binding site. Here, we applied a fragment-based high-throughput screening (HTS) strategy to identify low molecular weight chemotypes capable of engaging with human CD28. A 3200-member library composed of structurally diverse fragments, enriched for scaffolds designed to target protein-protein interaction (PPI) interfaces, was screened in single-dose format using temperature-related intensity change (TRIC) technology, yielding 36 primary hits (1.13% hit rate). Follow-up surface plasmon resonance (SPR) validation confirmed two fragments as direct CD28 binders. Molecular docking analysis revealed a plausible binding orientation for PPIF3 within the CD28 extracellular domain, suggesting potential interaction hotspots that may be exploited during future optimization. Together, these findings provide the first demonstration that fragment-based screening can successfully identify chemotypes capable of engaging with the CD28 PPI interface. This work establishes a scalable, biophysics-driven workflow for CD28 ligand discovery and lays the foundation for subsequent hit-to-lead development of small molecule CD28 modulators.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"46 ","pages":"Article 102542"},"PeriodicalIF":2.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147388234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Swimming exercise training (SET) and MitoQ supplementation can mitigate the atrophy and inflammation process in skeletal muscles of male Wistar rats with spinal cord injury (SCI): NF-κB/MuRF-1/proteasome pathway 游泳运动训练（SET）和补充MitoQ可通过NF-κB/MuRF-1/蛋白酶体途径缓解雄性Wistar大鼠脊髓损伤（SCI）骨骼肌萎缩和炎症过程。

IF 2.2

Biochemistry and Biophysics Reports Pub Date : 2026-06-01 Epub Date: 2026-05-25 DOI: 10.1016/j.bbrep.2026.102647

Zahra Behroozi , Beydolah Shahouzehi , Daruosh Moflehi , Mahdiyeh Moradi , Fatemeh Rastegari Nasab Ravari , Mahdiye Lashkari-Zadeh , Maryam Hadadi , Mohammad Mojtaba Farazi , Soheil Aminizadeh

{"title":"Swimming exercise training (SET) and MitoQ supplementation can mitigate the atrophy and inflammation process in skeletal muscles of male Wistar rats with spinal cord injury (SCI): NF-κB/MuRF-1/proteasome pathway","authors":"Zahra Behroozi , Beydolah Shahouzehi , Daruosh Moflehi , Mahdiyeh Moradi , Fatemeh Rastegari Nasab Ravari , Mahdiye Lashkari-Zadeh , Maryam Hadadi , Mohammad Mojtaba Farazi , Soheil Aminizadeh","doi":"10.1016/j.bbrep.2026.102647","DOIUrl":"10.1016/j.bbrep.2026.102647","url":null,"abstract":"<div><div>In the present study, we investigated the effects of a rehabilitation period with MitoQ supplement and swimming exercise training (SET) on atrophy and the inflammation process in the skeletal muscles of male rats with spinal cord injury (SCI). In the present study, rats were assigned to five groups (<em>n</em> = 7): Sham, SCI, SCI + SET, SCI + MitoQ (250 μM), and SCI + SET + MitoQ. In the training groups, the rats underwent swimming training for 4 weeks, 5 days/week. Motor function was assessed via the Basso, Beattie, and Bresnahan (BBB) locomotor scale method. The diameter of the skeletal muscle cells, along with the expression of the genes (NF-κB, MuRF-1, proteasome, and myostatin) and proteins (NF-κB, proteasome, and myostatin) were measured using hematoxylin and eosin (H&E) staining, real-time PCR (2<sup>−ΔΔCT</sup>), and Western blot analysis, respectively. Rsults: After 4 weeks, the BBB score in the SCI + MitoQ and SCI + SET + MitoQ groups did not return to normal levels compared to the sham group. MitoQ helped improve the motor function score compared to the SCI group (<em>p < </em>0.0001). In skeletal muscles, performing SET significantly decreased proteasome (<em>p < </em>0.0001) and myostatin (<em>p</em> = 0.0003) proteins, as well as myostatin and NF-kB gene expression compared to the SCI group (<em>p</em> = 0.02). SET, MitoQ, and the combination of treatments helped improve motor function and reduce muscle atrophy. Although MitoQ's antioxidant effect on reducing atrophy was not as strong as the combined treatment, it still led to better improvements in motor function.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"46 ","pages":"Article 102647"},"PeriodicalIF":2.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148154927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evolutionary divergence of nocturnin led to redox regulation in mammalian orthologs 夜曲蛋白的进化分化导致哺乳动物同源物的氧化还原调控

IF 2.2

Biochemistry and Biophysics Reports Pub Date : 2026-06-01 Epub Date: 2026-05-30 DOI: 10.1016/j.bbrep.2026.102643

Crystal A. Olivas-Rasmussen, Peng Gao, Emil S. Rasmussen, Carla B. Green

{"title":"Evolutionary divergence of nocturnin led to redox regulation in mammalian orthologs","authors":"Crystal A. Olivas-Rasmussen, Peng Gao, Emil S. Rasmussen, Carla B. Green","doi":"10.1016/j.bbrep.2026.102643","DOIUrl":"10.1016/j.bbrep.2026.102643","url":null,"abstract":"<div><div>NADP(H) and NAD(H) are essential cofactors involved in nearly 500 metabolic reactions, making them fundamental to cellular function and redox homeostasis. Loss of redox homeostasis through alterations in NADP(H) regulation has been implicated in various diseases, including neurodegenerative disorders and cardiovascular diseases. The levels of these metabolites are tightly regulated and highly compartmentalized. Nocturnin (NOCT), a circadian clock-controlled phosphatase, hydrolyzes both oxidized and reduced forms of NADP(H) and exists in cytosolic and mitochondrial forms. Here, we compare the activity of <em>Xenopus</em> and mammalian NOCT, which reveals a novel redox-dependent regulatory mechanism in mammals. Mammalian NOCT undergoes cysteine-mediated disulfide bond formation, leading to enzyme oligomerization and inactivation, while reduction of these cysteines restores NOCT to its monomeric, active form. In contrast, <em>Xenopus laevis</em> NOCT lacks these regulatory cysteines, does not oligomerize, and remains constitutively active. We show that oligomerization of mammalian NOCT occurs physiologically in the mitochondria while the comparatively highly reduced environment of the cytosol keeps NOCT in its monomeric conformation. Furthermore, sequence analysis reveals that mitochondrial NOCT emerges predominantly in mammals and coincides with the acquisition of redox-sensitive cysteines, highlighting a possible adaptation to oxidative metabolic environments. These findings suggest that mammalian NOCT functions as a redox sensor, dynamically modulating NADP(H) availability in response to oxidative stress. Understanding NOCT's evolution and regulation offers new insights into NADP(H) metabolism and its broader implications for oxidative stress.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"46 ","pages":"Article 102643"},"PeriodicalIF":2.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148167375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Preimplantation genetic testing for polygenic diseases: A novel paradigm in embryo selection 多基因疾病的植入前基因检测：胚胎选择的新范式

IF 2.2

Biochemistry and Biophysics Reports Pub Date : 2026-06-01 Epub Date: 2026-03-11 DOI: 10.1016/j.bbrep.2026.102532

Tianrui Jing , Yanzhi Du

{"title":"Preimplantation genetic testing for polygenic diseases: A novel paradigm in embryo selection","authors":"Tianrui Jing , Yanzhi Du","doi":"10.1016/j.bbrep.2026.102532","DOIUrl":"10.1016/j.bbrep.2026.102532","url":null,"abstract":"<div><div>Polygenic diseases are caused by a number of independently acting or interacting polymorphic genomic variants in conjunction with environmental factors, and show an increasing global prevalence, posing a significant threat to individual and public health. Given the limited curative prospects for polygenic diseases owing to their complex etiology, preventive strategies have gained paramount importance. Preimplantation genetic testing for polygenic disorders (PGT-P) is an advanced in vitro fertilization technique that screens embryos for genetic susceptibility to polygenic diseases, aiming to reduce the risk of offspring developing conditions such as diabetes, schizophrenia, polycystic ovary syndrome, and certain cancers. This technology calculates polygenic disease risks across sibling embryos relying on the use of a polygenic risk score (PRS) that counts the effects of risk alleles derived from genome-wide association studies. Using PGT-P, each embryo's PRS is computed for any disease or trait of interest, and the euploid embryo with the lowest PRS is prioritized for implantation. As a result, PGT-P may decrease the disease risk for future offspring and provide a novel strategy for embryo ranking, selection, or even discarding. In this review, we systematically summarize the current knowledge regarding PGT-P, detailing its workflow, potential benefits, predictive power, expected risk reduction and significant limitations. We further evaluate its utility and practical implementation in clinical practice and outline critical directions for future research.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"46 ","pages":"Article 102532"},"PeriodicalIF":2.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147388217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0