SGDAcn is a suppressor for silk gland endoreplication and development

Insect Science, Год журнала: 2025, Номер unknown

Опубликована: Март 16, 2025

Abstract Silkworm silk gland cells undergo multiple rounds of endoreplication, a process in which the genome is duplicated without cell division, leading to cellular polyploidization. This results accumulation genomic DNA, serving as foundation for rapid proteins synthesis. For first time, we report previously uncharacterized gene, SGDAcn , silkworm that clustered regularly interspaced short palindromic repeats (CRISPR) / CRISPR‐associated nuclease 9‐mediated knockout posterior increased size and enhanced production. facilitated progression endoreplication by upregulating expression various cyclin genes promoting energy metabolism, substantial increase fibroin gene its transcription factor Dimm well stimulation ribosome biogenesis messenger RNA translation enhancement eukaryotic initiation factors protein Our findings demonstrate influences growth, nucleolus through ‐EGFR/PI3K/AKT ‐NF‐ κ B signaling pathways. Overall, acts negative regulator development, affecting synthesis, thus modulating These mechanisms might be conserved growth progression, making an attractive target genetic editing improve yield silkworms potentially mammalian regulation.

Язык: Английский

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Sphaeropsidin A covalently binds to Cys 151 of Keap1 to attenuate LPS-induced acute pneumonia in mice

Redox Biology, Год журнала: 2025, Номер unknown, С. 103621 - 103621

Опубликована: Март 1, 2025

Kelch ECH-associating protein 1 (Keap1)-Nuclear factor erythroid 2-related 2 (Nrf2) axis is crucial for regulating oxidative stress and inflammatory responses in acute pneumonia. Sphaeropsidin A (SA) a antioxidant diterpenoid isolated from Sphaeropsis sapinea f. sp. cupressi, discovered as novel Nrf2 agonist by our research group previously. However, the accurate function mechanism of SA treating pneumonia are still unknown. The therapeutic effect was evaluated LPS-induced mice. underlying action then analyzed transcriptomics. direct target identified through synthesis SA-biotin probe, binding amino acid residues were found verified LC-MS/MS analysis site-specific mutation. Finally, knockout mice employed to verify SA. Our data indicated that significantly inhibited via up-regulating Nrf2, inhibiting NLRP3 inflammasome NF-κB activation, Keap1 Specifically, effective dose only mg/kg. selectively covalent bound cysteine 151 residue (Cys151). mediated activation reduced level ROS, thereby inflammasome. Besides, formed hydrogen bond with ASP48 ASC, blocking its oligomerization This study indicates might be new molecule activate promising drug candidate or lead therapy Nrf2/NF-κB/NLRP3 axis.

Язык: Английский

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The multifaceted roles of the transcriptional coactivator TAZ in extravillous trophoblast development of the human placenta

Proceedings of the National Academy of Sciences, Год журнала: 2025, Номер 122(16)

Опубликована: Апрель 14, 2025

Insights into the molecular processes that drive early development of human placenta is crucial for our understanding pregnancy complications such as preeclampsia and fetal growth restriction, since defects in maturation its epithelial cell, trophoblast, have been detected severe forms these diseases. However, key regulators specifying differentiated trophoblast subtypes are only slowly emerging. By using diverse cell models, we herein show transcriptional coactivator HIPPO signaling, TAZ, plays a pivotal role invasive extravillous trophoblasts (EVTs), cells essential decidual vessel remodeling adaption maternal blood flow to placenta. Ribonucleic acid sequencing (RNA-seq) or protein analyses upon TAZ gene silencing CRISPR-Cas9-mediated knockout differentiating stem cells, organoids, primary EVTs, choriocarcinoma villous explant cultures unraveled promoted expression genes associated with EVT identity, motility, survival. Accordingly, depletion chemical inhibition interacting TEA domain family member 1 (TEAD1), impaired differentiation, invasion, migration triggered apoptosis different models. Notably, also suppressed cycle self-renewal prevented EVTs from fusion organoids cultures. Moreover, leukocyte antigen G (HLA-G) surface increased NUAK1 kinase thereby maintaining own expression. In summary, multifaceted lineage by controlling biological initiate preserve differentiation.

Язык: Английский

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TAZ deficiency impairs the autophagy-lysosomal pathway through NRF2 dysregulation and lysosomal dysfunction

International Journal of Biological Sciences, Год журнала: 2024, Номер 20(7), С. 2592 - 2606

Опубликована: Янв. 1, 2024

Transcriptional coactivator with a PDZ-binding motif (TAZ) plays key role in normal tissue homeostasis and tumorigenesis through interaction several transcription factors. In particular, TAZ deficiency causes abnormal alveolarization emphysema, persistent overexpression contributes to lung cancer pulmonary fibrosis, suggesting the possibility of complex mechanism function. Recent studies suggest that nuclear factor erythroid 2-related 2 (NRF2), an antioxidant defense system, induces expression during also activates NRF2-mediated pathway. We thus thought elucidate cross-regulation NRF2 underlying molecular mechanisms functions. directly interacted N-terminal domain suppressed transcriptional activity by preventing from binding DNA. addition, return basal levels after signaling was inhibited deficiency, resulting sustained aberrantly increased targets. failed modulate optimal concomitantly impaired lysosomal acidification enzyme function, accumulating autophagy vesicles reactive oxygen species causing protein oxidation cellular damage lungs. restoration normalized dysregulated aberrant function triggered autophagy-lysosomal Therefore, is indispensable for regulation pathways caused oxidative stress oxidized proteins.

Язык: Английский

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Curcumin loaded hydrogel with double ROS-scavenging effect regulates microglia polarization to promote poststroke rehabilitation

Materials Today Bio, Год журнала: 2024, Номер 28, С. 101177 - 101177

Опубликована: Авг. 2, 2024

Cyclodextrins are used to include curcumin form complex, which is subsequently loaded into a reactive oxygen species (ROS) responsive hydrogel (Cur gel). This gel exhibits dual ROS scavenging effect. The can neutralize extracellular lead ROS-sensitive release. released complex eliminate intracellular ROS. Furthermore, the Cur effectively downregulates expression of CD16 and IL-1β while upregulating CD206 TGF-β in glucose-deprived (OGD) BV2 cells. Additionally, it restores synaptophysin PSD95 OGD N2a Upon injection stroke cavity, reduces increases peri-infarct area mice, indicating an

Язык: Английский

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Omentin-1 ameliorates experimental inflammatory bowel disease via Nrf2 activation and redox regulation

Life Sciences, Год журнала: 2023, Номер 328, С. 121847 - 121847

Опубликована: Июнь 7, 2023

Язык: Английский

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Opioids Alleviate Oxidative Stress via the Nrf2/HO-1 Pathway in LPS-Stimulated Microglia

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(13), С. 11089 - 11089

Опубликована: Июль 4, 2023

Opioids are known to have antioxidant effects and modulate microglial function under certain conditions. It has been previously shown that opioid ligands can effectively inhibit the release of proinflammatory cytokines when stimulated with lipopolysaccharide (LPS) convert microglia an anti-inflammatory polarization state. Here, we used C8-B4 cells, mouse cell line activated by LPS as a model investigate anti-inflammatory/antioxidant potential selected receptor agonists (DAMGO, DADLE, U-50488). We found all these could exert cytoprotective through mechanism affecting LPS-induced ROS production, NADPH synthesis, glucose uptake. Interestingly, opioids elevated level reduced glutathione, increased ATP content, enhanced mitochondrial respiration in cells exposed LPS. These beneficial were associated upregulation Nrf2/HO-1 pathway. The present results indicate activation signaling supports preservation concomitant elimination suggest pathway-dependent is involved efficacy opioids. Opioid may therefore be considered agents suppress oxidative stress inflammatory responses microglia.

Язык: Английский

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Design, synthesis fusidic acid derivatives alleviate acute lung injury via inhibiting MAPK/NF-κB/NLRP3 pathway

European Journal of Medicinal Chemistry, Год журнала: 2023, Номер 259, С. 115697 - 115697

Опубликована: Авг. 1, 2023

Язык: Английский

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YES1 as a potential target to overcome drug resistance in EGFR-deregulated non-small cell lung cancer

Archives of Toxicology, Год журнала: 2024, Номер 98(5), С. 1437 - 1455

Опубликована: Март 5, 2024

Язык: Английский

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The interplay between hippo signaling and mitochondrial metabolism: Implications for cellular homeostasis and disease

Mitochondrion, Год журнала: 2024, Номер 76, С. 101885 - 101885

Опубликована: Апрель 21, 2024

Язык: Английский

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