Precise genome editing of the Kozak sequence enables bidirectional and quantitative modulation of protein translation to anticipated levels without affecting transcription DOI Creative Commons

Jingke Xie,

Zhenpeng Zhuang,

Shixue Gou

et al.

Nucleic Acids Research, Journal Year: 2023, Volume and Issue: 51(18), P. 10075 - 10093

Published: Aug. 10, 2023

None of the existing approaches for regulating gene expression can bidirectionally and quantitatively fine-tune to desired levels. Here, on basis precise manipulations Kozak sequence, which has a remarkable influence translation initiation, we proposed validated novel strategy directly modify upstream nucleotides initiation codon given flexibly alter level by using base editors prime editors. When three (named KZ3, part sequence), exhibits most significant preference were selected as editing region levels proteins, confirmed that each 64 KZ3 variants had different efficiency, but all similar transcription Using ranked with efficiencies predictors, editor- editor-mediated mutations in local genome could anticipated without affecting vitro vivo. Notably, this be extended whole sequence applied protein-coding genes eukaryotes.

Language: Английский

Targeting protein modifications in metabolic diseases: molecular mechanisms and targeted therapies DOI Creative Commons
Xiumei Wu, Mengyun Xu,

M. Geng

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 27, 2023

The ever-increasing prevalence of noncommunicable diseases (NCDs) represents a major public health burden worldwide. most common form NCD is metabolic diseases, which affect people all ages and usually manifest their pathobiology through life-threatening cardiovascular complications. A comprehensive understanding the will generate novel targets for improved therapies across spectrum. Protein posttranslational modification (PTM) an important term that refers to biochemical specific amino acid residues in target proteins, immensely increases functional diversity proteome. range PTMs includes phosphorylation, acetylation, methylation, ubiquitination, SUMOylation, neddylation, glycosylation, palmitoylation, myristoylation, prenylation, cholesterylation, glutathionylation, S-nitrosylation, sulfhydration, citrullination, ADP ribosylation, several PTMs. Here, we offer review roles pathological consequences, including diabetes, obesity, fatty liver hyperlipidemia, atherosclerosis. Building upon this framework, afford description proteins pathways involved by focusing on PTM-based protein modifications, showcase pharmaceutical intervention preclinical studies clinical trials, future perspectives. Fundamental research defining mechanisms whereby regulate open new avenues therapeutic intervention.

Language: Английский

Citations

99
Lysosomal control of senescence and inflammation through cholesterol partitioning DOI
Kyeonghwan Roh, Jeonghwan Noh, Yeonju Kim

et al.

Nature Metabolism, Journal Year: 2023, Volume and Issue: 5(3), P. 398 - 413

Published: March 2, 2023

Language: Английский

Citations

67
25-Hydroxycholesterol regulates lysosome AMP kinase activation and metabolic reprogramming to educate immunosuppressive macrophages DOI
Jun Xiao, Shuang Wang, Longlong Chen

et al.

Immunity, Journal Year: 2024, Volume and Issue: 57(5), P. 1087 - 1104.e7

Published: April 18, 2024

Language: Английский

Citations

40
Bioactive Components of Areca Nut: An Overview of Their Positive Impacts Targeting Different Organs DOI Open Access

Huihui Sun,

Wenzhen Yu,

Hu Li

et al.

Nutrients, Journal Year: 2024, Volume and Issue: 16(5), P. 695 - 695

Published: Feb. 29, 2024

Areca catechu L. is a widely cultivated tropical crop in Southeast Asia, and its fruit, areca nut, has been consumed as traditional Chinese medicinal material for more than 10,000 years, although it recently attracted widespread attention due to potential hazards. nut holds significant position medicine many areas ranks first among the four southern medicines China. Numerous bioactive compounds have identified nuts, including alkaloids, polyphenols, polysaccharides, fatty acids, which exhibit diverse functions, such anti-bacterial, deworming, anti-viral, anti-oxidant, anti-inflammatory, anti-tumor effects. Furthermore, they also display beneficial impacts targeting nervous, digestive, endocrine systems. This review summarizes pharmacological functions underlying mechanisms of ingredients nut. helps ascertain components discover potential, guide utilization

Language: Английский

Citations

23
High‐Throughput Formation of Pre‐Vascularized hiPSC‐Derived Hepatobiliary Organoids on a Chip via Nonparenchymal Cell Grafting DOI Creative Commons
Han Fan, J. K. Shang, Junbo Li

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 4, 2025

Abstract Liver organoids have been increasingly adopted as a critical in vitro model to study liver development and diseases. However, the pre‐vascularization of without affecting parenchymal specification remains long‐lasting challenge, which is essential for their application regenerative medicine. Here, large‐scale formation pre‐vascularized human hepatobiliary (vhHBOs) presented epithelial via novel strategy, namely nonparenchymal cell grafting (NCG). Endothelial mesenchymal cells are grafted (hHBOs) at different differentiation stages supplementing with culture medium growth factors. stage hepatic maturation offers an optimal integration efficiency compared specification. Additionally, proves crucial endothelial invading sprouting into during establishment vhHBOs. Ectopic implants mice further displayed vhHBOs vascular networks. Notably, transplanted self‐organized native tissue like zone bile ducts, indicating potential regenerate damaged duct tissues. It believed that will offer technical route form high‐fidelity complex engineering

Language: Английский

Citations

3
Plasma proteomic signatures of social isolation and loneliness associated with morbidity and mortality DOI Creative Commons
Chun Shen, Ruohan Zhang, Jin‐Tai Yu

et al.

Nature Human Behaviour, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

Language: Английский

Citations

2
A Hypothesis That Glucagon-like Peptide-1 Receptor Agonists Exert Immediate and Multifaceted Effects by Activating Adenosine Monophosphate-Activate Protein Kinase (AMPK) DOI Creative Commons
C. Mary Schooling, Guoyi Yang, Ghada A. Soliman

et al.

Life, Journal Year: 2025, Volume and Issue: 15(2), P. 253 - 253

Published: Feb. 7, 2025

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce bodyweight and blood glucose. Extensive evidence from randomized controlled trials has indicated that GLP-1RAs have benefits well beyond weight loss glucose control, extending reductions in cardiovascular mortality to prostate cancer risk. Notably, some of for the cardiovascular–kidney–metabolic (CKM) system arise before occurs reasons are not entirely clear but key patient care drug development. Here, we hypothesize act by inducing calorie restriction activating adenosine monophosphate-activated protein kinase (AMPK), which only provides an explanation unique effectiveness also indicates a common mechanism shared effective CKM therapies, including salicylates, metformin, statins, healthy diet, physical activity. Whether AMPK activation is obligatory therapies should be considered. As such, propose action explain how it overarching framework identifying means preventing treating cardiovascular, kidney, metabolic related diseases, as informing complementary question components lifestyle.

Language: Английский

Citations

2
SIRT1/SREBPs-mediated regulation of lipid metabolism DOI Creative Commons
Shan Shen, Mingyang Shen,

Lirun Kuang

et al.

Pharmacological Research, Journal Year: 2023, Volume and Issue: 199, P. 107037 - 107037

Published: Dec. 7, 2023

Sirtuins, also called silent information regulator 2, are enzymes that rely on nicotinamide adenine dinucleotide (NAD+) to function as histone deacetylases. Further investigation is warranted explore the advantageous impacts of Sirtuin 1 (SIRT1), a constituent sirtuin group, lipid metabolism, in addition its well-researched involvement extending lifespan. The regulation gene expression has been extensively linked SIRT1. Sterol regulatory element-binding protein (SREBP) substrate SIRT1 attracted significant interest due role multiple cellular processes including cell cycle regulation, DNA damage repair, and metabolic functions. Hence, objective this analysis was investigate elucidate correlation between SREBPs, well assess contribution SIRT1/SREBPs mitigating metabolism dysfunction. research whether SREBPs could be utilized viable targets for therapeutic intervention managing complications associated with diabetes.

Language: Английский

Citations

40
GLSP and GLSP-derived triterpenes attenuate atherosclerosis and aortic calcification by stimulating ABCA1/G1-mediated macrophage cholesterol efflux and inactivating RUNX2-mediated VSMC osteogenesis DOI Creative Commons

Guobin Zheng,

Yun Zhao, Zhenhao Li

et al.

Theranostics, Journal Year: 2023, Volume and Issue: 13(4), P. 1325 - 1341

Published: Jan. 1, 2023

Background and Purpose: Atherosclerosis is the main pathophysiological foundation of cardiovascular disease, which was caused by inflammation lipid metabolism disorder, along with vascular calcification.Aortic calcification leads to reduced plaque stability eventually causes rupture events.Presently, drug treat aortic remains not be available.Ganoderma lucidum spore powder (GLSP) from Ganoderma a Traditional Chinese Medicine homology medicine food.It has multiple pharmacological effects, but no research on during atherosclerosis performed.This study investigated effects GLSP revealed underlying mechanism.Methods: In vivo, 8-week-aged male LDLR -/-mice were fed high-fat diet induce calcification.Simultaneously, mice treated at first week HFD feeding determine protection against early advanced atherosclerosis.Subsequently, tissues collected evaluate atherosclerosis, calcification, reveal mechanism.In vitro, we determined major components triterpenes HPLC, subsequently assessed protective these active metabolism, inflammation, in RAW264.7 HASMC cells.Results: We observed attenuated area atherosclerosis.GLSP number foam cells improving ABCA1/G1-mediated cholesterol efflux macrophages.In addition, protected endothelium activation.Moreover, inhibited inactivating RUNX2-mediated osteogenesis HASMCs.Furthermore, triterpenes, including Ganoderic acid A, B, C6, G, Ganodermanontriol, found that promoted macrophage, inactivated VSMC.Conclusions: This demonstrates attenuates Ivyspring

Language: Английский

Citations

27
Deficiency of ASGR1 promotes liver injury by increasing GP73-mediated hepatic endoplasmic reticulum stress DOI Creative Commons
Zhe Zhang,

X. Leng,

Yuan Yuan Zhai

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 8, 2024

Abstract Liver injury is a core pathological process in the majority of liver diseases, yet genetic factors predisposing individuals to its initiation and progression remain poorly understood. Here we show that asialoglycoprotein receptor 1 (ASGR1), lectin specifically expressed liver, downregulated patients with fibrosis or cirrhosis male mice injury. ASGR1 deficiency exacerbates while overexpression mitigates acetaminophen-induced acute CCl4-induced chronic injuries mice. Mechanistically, binds an endoplasmic reticulum stress mediator GP73 facilitates lysosomal degradation. depletion increases circulating levels promotes interaction between BIP activate stress, leading Neutralization not only attenuates deficiency-induced but also improves survival received lethal dose acetaminophen. Collectively, these findings identify as potential determinant susceptibility propose it therapeutic target for treatment

Language: Английский

Citations

14