RERconverge Expansion: Using Relative Evolutionary Rates to Study Complex Categorical Trait Evolution DOI Creative Commons
Ruby Redlich, Amanda Kowalczyk,

Michael Tene

et al.

Molecular Biology and Evolution, Journal Year: 2024, Volume and Issue: 41(11)

Published: Oct. 15, 2024

Comparative genomics approaches seek to associate molecular evolution with the of phenotypes across a phylogeny. Many these methods lack ability analyze non-ordinal categorical traits more than two categories. To address this limitation, we introduce an expansion RERconverge that associates shifts in evolutionary rates convergent traits. The includes for performing ancestral state reconstruction, statistical tests associating relative variables, and new method phylogeny-aware permutations, "permulations", on We demonstrate our three-category diet phenotype, compare its performance binary analyses existing comparative genomic traits: phylogenetic simulations signal based method. present analysis how permulations scale number species categories included analysis. Our results show outperforms at identifying genes enriched pathways significantly associated reconstruction drives improvement capture diet-related compared when implemented without user input phenotype evolution. will provide strong foundation applying larger data sets complex trait have previously been analyzed.

Language: Английский

Research progress on PIEZO1 protein structure and activation mechanism by small-molecule agonists DOI Creative Commons
D. Li, Yuanyuan Song, Yuan Zeng

et al.

Results in Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 102058 - 102058

Published: Jan. 1, 2025

Language: Английский

Citations

0
Piezo1 promotes the progression of necrotizing enterocolitis by activating the Ca2(+)/CaMKII-dependent pathway DOI Creative Commons
Zhenyu Li, Qinlei Jiang,

Jiaqi Wei

et al.

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: March 12, 2025

Necrotizing enterocolitis (NEC) is a devastating inflammatory bowel necrosis of preterm infants with limited therapeutic approaches. Mounting evidence supports the role Piezo1, namely, widely distributed mechanosensor in intestinal epithelial cells (IECs), inflammation but its underlying mechanism development NEC remains unexplored. In this study, we demonstrated that Piezo1 expression was higher lower gestational age. C57BL/6J mice wherein deleted IECs (villin-specific knockout mice; Piezo1flox/floxVillinCre+) and Piezo1flox/flox littermates were subjected to induce NEC, regulated barrier function, restricted cytokines secretion, diminished response mouse models. elevated cytosolic Ca2+ levels activated Ca2+/calmodulin-dependent protein kinase II (CaMKII) promote CaMKII/NF-κB interaction NF-κB activation vitro. Finally, effects CaMKII inhibitor, KN93, evaluated both vitro vivo models, functions suppressed partially by KN93. characterise undefined which may be attributed differential calcium under pathophysiological conditions. Intestinal regulates secretion necrotizing enterocolitis.

Language: Английский

Citations

0
Endothelial Piezo1 stimulates angiogenesis to offer protection against intestinal ischemia–reperfusion injury in mice DOI Creative Commons

Cuifen Wang,

Shangfei Luo,

Yameng Yan

et al.

Molecular Medicine, Journal Year: 2025, Volume and Issue: 31(1)

Published: April 22, 2025

Abstract Background Intestinal ischemia–reperfusion (I/R) injury, which occurs in the ileum and not only leads to intestinal tissue damage, but also may trigger systemic inflammatory responses, is a prevalent pathological condition that typically associated with acute ischemia, surgical procedures, or trauma. However, precise underlying pathogenic mechanisms have yet been fully uncovered. In this study, we explored specific roles by endothelial Piezo1 involved I/R injury. Methods We evaluated of using both vivo mouse injury vitro hypoxia-reoxygenation (H/R) models. The expression was assessed immunofluorescence RT-qPCR. experiments involving knockout activation agonist Yoda1 were conducted observe effects on angiogenesis Results found post-intestinal mice, markedly increased mainly abundant cells. Specific exhibited more severe phenotype characterized accelerating damage structure, increasing response, inhibiting angiogenesis. Yoda1-mediated significantly ameliorated Activation induced H/R promoted Human Umbilical Vein Endothelial Cells (HUVECs), inhibited GsMTx4. mediated linked an increase extracellular Ca 2+ influx, turn enhanced hypoxia-inducible factor 1 alpha (HIF-1α) signaling pathway. Conclusions Our findings indicate plays crucial role protecting against promoting cells, possibly through /HIF-1α/VEGF This suggests targeting channels could be therapeutic strategy for

Language: Английский

Citations

0
The role of mechanically sensitive ion channel Piezo1 in bone remodeling DOI Creative Commons

Yugui Du,

Bowen Xu,

Quiying Li

et al.

Frontiers in Bioengineering and Biotechnology, Journal Year: 2024, Volume and Issue: 12

Published: Feb. 8, 2024

Piezo1 (2010) was identified as a mechanically activated cation channel capable of sensing various physical forces, such tension, osmotic pressure, and shear force. mediates mechanosensory transduction in different organs tissues, including its role maintaining bone homeostasis. This review aimed to summarize the function possible mechanism mechanical receptor cells tissue. We found that it is potential therapeutic target for treatment diseases.

Language: Английский

Citations

3
Mechano-sensor Piezo1 inhibits glucagon production in pancreatic α-cells DOI

Wenying Guo,

Luyang Gao, Haocong Mo

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2024, Volume and Issue: 1870(5), P. 167185 - 167185

Published: April 21, 2024

Language: Английский

Citations

3
Epithelial Piezo1 deletion ameliorates intestinal barrier damage by regulating ferroptosis in ulcerative colitis DOI
Jiejie Zhu,

Yumei Wu,

Luyao Zhang

et al.

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 224, P. 272 - 286

Published: Aug. 29, 2024

Language: Английский

Citations

3
Ion channels in macrophages: Implications for disease progression DOI
Li Xu, Yuzhe Du,

Chunlei Yu

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 144, P. 113628 - 113628

Published: Nov. 19, 2024

Language: Английский

Citations

1
Hydrogel-Integrated Millifluidic Systems: Advancing the Fabrication of Mucus-Producing Human Intestinal Models DOI Creative Commons
Ahed Almalla,

Nadra Alzain,

Laura Elomaa

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(13), P. 1080 - 1080

Published: June 21, 2024

The luminal surface of the intestinal epithelium is protected by a vital mucus layer, which essential for lubrication, hydration, and fostering symbiotic bacterial relationships. Replicating studying this complex structure in vitro presents considerable challenges. To address this, we developed hydrogel-integrated millifluidic tissue chamber capable applying precise apical shear stress to models cultured on flat or 3D structured hydrogel scaffolds with adjustable stiffness. designed accommodate nine scaffolds, 3D-printed as disks storage modulus matching physiological range stiffness (~3.7 kPa) from bioactive decellularized methacrylated small submucosa (dSIS-MA). Computational fluid dynamics simulations were conducted confirm laminar flow profile both villi-comprising physiologically relevant regime. system was initially validated HT29-MTX seeded demonstrating accelerated differentiation, increased production, enhanced organization under stress. These characteristic features are advanced they critically contribute functional barrier. Subsequently, challenged human stem cells (ISCs) terminal ileum. Our findings indicate that biomimicking combination stress, promote multi-lineage evidenced gene protein expression analysis basic markers structural ISCs absence chemical differentiation triggers. quantitative alkaline phosphatase (ALP) activity secreted demonstrates into enterocyte goblet cell lineages. system, has been optimized performance cost efficiency, enables creation modulation conditions, including tunable matrix varying stresses. Moreover, readily accessible scalable mucus-producing cellular permit comprehensive investigation pathogen interactions penetration, thereby offering potential advance our understanding health disease.

Language: Английский

Citations

0
Forces Bless You: Mechanosensitive Piezo Channels in Gastrointestinal Physiology and Pathology DOI Creative Commons
Jing Guo, Li Li,

F. G. Chen

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(7), P. 804 - 804

Published: July 7, 2024

The gastrointestinal (GI) tract is an organ actively involved in mechanical processes, where it detects forces via a mechanosensation mechanism. Mechanosensation relies on specialized cells termed mechanoreceptors, which convert into electrochemical signals mechanosensors. mechanosensitive Piezo1 and Piezo2 are widely expressed various that respond to GI by altering transmembrane ionic currents, such as epithelial cells, enterochromaffin intrinsic extrinsic enteric neurons. This review highlights recent research advances Piezo channels physiology pathology. Specifically, the latest insights role of intestinal barrier, motility, summarized. Additionally, overview pathogenesis disorders, including irritable bowel syndrome, inflammatory disease, cancers, provided. Overall, presence offers promising new perspective for treatment disorders.

Language: Английский

Citations

0
RERconverge Expansion: Using Relative Evolutionary Rates to Study Complex Categorical Trait Evolution DOI Creative Commons
Ruby Redlich, Amanda Kowalczyk,

Michael Tene

et al.

Molecular Biology and Evolution, Journal Year: 2024, Volume and Issue: 41(11)

Published: Oct. 15, 2024

Comparative genomics approaches seek to associate molecular evolution with the of phenotypes across a phylogeny. Many these methods lack ability analyze non-ordinal categorical traits more than two categories. To address this limitation, we introduce an expansion RERconverge that associates shifts in evolutionary rates convergent traits. The includes for performing ancestral state reconstruction, statistical tests associating relative variables, and new method phylogeny-aware permutations, "permulations", on We demonstrate our three-category diet phenotype, compare its performance binary analyses existing comparative genomic traits: phylogenetic simulations signal based method. present analysis how permulations scale number species categories included analysis. Our results show outperforms at identifying genes enriched pathways significantly associated reconstruction drives improvement capture diet-related compared when implemented without user input phenotype evolution. will provide strong foundation applying larger data sets complex trait have previously been analyzed.

Language: Английский

Citations

0