Cholic acid mitigates osteoarthritis by inhibiting the NF-κB/PERK/SIRT1 signaling pathway DOI Open Access

JIAOE SHENG,

ZUMIN YI,

SANSHAN HE

et al.

Biocell, Journal Year: 2024, Volume and Issue: 48(7), P. 1095 - 1104

Published: Jan. 1, 2024

Introduction: Cholic acid (CA) is a natural steroid useful in treating chronic bronchitis and cholecystitis.On the other hand, its potential impact on osteoarthritis (OA) unknown.Objective: Using an vitro vivo model, we sought to assess chondroprotective properties of CA.Methods: We employed Cell Counting Kit-8 measure CA chondrocyte activity toxicity cells.Multiple molecular biology experimental techniques were used investigate signaling pathways that may use prevent inflammation give chondrocytes protection.Furthermore, how affects OA model Sprague-Dawley (SD) rats was evaluated.Results: significantly suppressed up-regulation interleukin-1 β (IL-1β), cyclooxygenase-2 (COX-2), matrix metalloproteinase 13 (MMP-13) downregulation aggrecan type II collagen A1 (COL2A) treated tumor necrosis factor-alpha (TNF-α).Differentially expressed genes (DEG) enrichment revealed IL-17, TNF, chemokine, cytokine-cytokine receptor, toll-like nucleotide oligomerization domain-like receptor primary pathways.The enriched DEGs included CXCL6, CCL20, MMP3, CXCL3, CXCL11, CCL5, CXCL10, MMP9, MMP13, CXCL2; these are involved inflammatory responses their expression induced by TNF-α reversed treatment.CA inhibits p65 nuclear translocation inhibitory subunit kappa B alpha (IκBα) phosphorylation TNF-α.Furthermore, attenuated protein kinase RNA-like endoplasmic reticulum (PERK), inositolrequiring transmembrane kinase/endoribonuclease 1α (IRE1α), glucose regulatory 78 (GRP78), sirtuin 1 (SIRT1), down-regulation AMP-activated kinase-α (p-AMPKα) TNF-α-treated chondrocytes.Conclusions: ameliorated cartilage degradation rat model.CA alleviated response through factor B/PERK/SIRT1 axis degradation.

Language: Английский

Lumican promotes calcific aortic valve disease through H3 histone lactylation DOI
Yuming Huang, Chunli Wang, Tingwen Zhou

et al.

European Heart Journal, Journal Year: 2024, Volume and Issue: 45(37), P. 3871 - 3885

Published: July 8, 2024

Abstract Background and Aims Valve interstitial cells (VICs) undergo a transition to intermediate state before ultimately transforming into the osteogenic cell population, which is pivotal cellular process in calcific aortic valve disease (CAVD). Herein, this study successfully delineated stages of VIC transformation elucidated novel key regulatory role lumican (LUM) process. Methods Single-cell RNA-sequencing (scRNA-seq) from nine human valves was used characterize pathological switch identify factors. The vitro, ex vivo, double knockout mice were constructed further unravel calcification-promoting effect LUM. Moreover, multi-omic approaches employed analyse molecular mechanism LUM CAVD. Results ScRNA-seq highlighted significance as molecule pro-calcification confirmed on vivo level, ApoE−/−//LUM−/− mice. induces osteogenesis VICs via activation inflammatory pathways augmentation glycolysis, resulting accumulation lactate. Subsequent investigation has unveiled driving histone modification, lactylation, plays facilitating calcification. More importantly, identified two specific sites namely, H3K14la H3K9la, have been found facilitate confirmation these modification sites’ association with expression genes Runx2 BMP2 achieved through ChIP-PCR analysis. Conclusions presents findings, being first establish involvement mediating H3 thus development Consequently, would be promising therapeutic target for intervention treatment

Language: Английский

Citations

47
Lactylome Analysis Unveils Lactylation‐Dependent Mechanisms of Stemness Remodeling in the Liver Cancer Stem Cells DOI Creative Commons
Fan Feng,

Jiaqin Wu,

Qingjia Chi

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(38)

Published: Aug. 5, 2024

Lactate plays a critical role as an energy substrate, metabolite, and signaling molecule in hepatocellular carcinoma (HCC). Intracellular lactate-derived protein lysine lactylation (Kla) is identified contributor to the progression of HCC. Liver cancer stem cells (LCSCs) are believed be root cause phenotypic functional heterogeneity However, impact Kla on biological processes LCSCs remains poorly understood. Here enhanced glycolytic metabolism, lactate accumulation, elevated levels observed compared HCC cells. H3K56la was found closely associated with tumourigenesis stemness LCSCs. Notably, comprehensive examination lactylome proteome ALDOA K230/322 lactylation, which promoting Furthermore, this study demonstrated tight binding between aldolase A (ALDOA) dead box deconjugate enzyme 17 (DDX17), attenuated by ultimately enhancing regulatory function DDX17 maintaining This investigation highlights significance modulating its Targeting may offer promising therapeutic approach for treating

Language: Английский

Citations

37
Crossing epigenetic frontiers: the intersection of novel histone modifications and diseases DOI Creative Commons

Weiyi Yao,

Xinting Hu,

Xin Wang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Sept. 16, 2024

Abstract Histone post-translational modifications (HPTMs), as one of the core mechanisms epigenetic regulation, are garnering increasing attention due to their close association with onset and progression diseases potential targeted therapeutic agents. Advances in high-throughput molecular tools abundance bioinformatics data have led discovery novel HPTMs which similarly affect gene expression, metabolism, chromatin structure. Furthermore, a growing body research has demonstrated that histone also play crucial roles development various diseases, including cancers, cardiovascular infectious psychiatric disorders, reproductive system diseases. This review defines nine modifications: lactylation, citrullination, crotonylation, succinylation, SUMOylation, propionylation, butyrylation, 2-hydroxyisobutyrylation, 2-hydroxybutyrylation. It comprehensively introduces modification processes these HPTMs, transcription, replication, DNA repair recombination, structure, well involvement promoting occurrence clinical applications targets biomarkers. Moreover, this provides detailed overview HPTM inhibitors targeting emerging strategies treatment multiple while offering insights into future prospects challenges. Additionally, we briefly introduce techniques field research.

Language: Английский

Citations

18
Rapid identification of Astragalus membranaceus processing with rice water based on intelligent color recognition and multi-source information fusion technology DOI Open Access
Dongmei Guo,

Yijing Pan,

Shunshun Wang

et al.

Chinese Herbal Medicines, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

6
Lactylation in health and disease: physiological or pathological? DOI Creative Commons
Lijun Zhao,

Haonan Qi,

Huiying Lv

et al.

Theranostics, Journal Year: 2025, Volume and Issue: 15(5), P. 1787 - 1821

Published: Jan. 2, 2025

Lactate is an indispensable substance in various cellular physiological functions and plays regulatory roles different aspects of energy metabolism signal transduction. Lactylation (Kla), a key pathway through which lactate exerts its functions, has been identified as novel posttranslational modification (PTM). Research indicates that Kla essential balancing mechanism variety organisms involved many biological processes pathways. closely related to disease development represents potential important new drug target. In line with existing reports, we searched for newly discovered sites on histone nonhistone proteins; reviewed the mechanisms (particularly focusing enzymes directly reversible regulation Kla, including "writers" (modifying enzymes), "readers" (modification-binding "erasers" (demodifying enzymes); summarized crosstalk between PTMs help researchers better understand widespread distribution diverse functions. Furthermore, considering "double-edged sword" role both pathological contexts, this review highlights "beneficial" states (energy metabolism, inflammatory responses, cell fate determination, development, etc.) "detrimental" pathogenic or inducive effects processes, particularly malignant tumors complex nontumor diseases. We also clarify molecular health disease, discuss feasibility therapeutic Finally, describe detection technologies their applications diagnosis clinical settings, aiming provide insights treatment diseases accelerate translation from laboratory research practice.

Language: Английский

Citations

2
Palmatine Retards Calcific Aortic Valve Disease Progression Targeting Gapdh K263 Lactylation Interfering with Glycolytic Metabolism DOI

Jiaqin Wu,

Shunshun Wang, Qianqian Du

et al.

Published: Jan. 1, 2025

Language: Английский

Citations

1
Novel acyl hydrazide derivatives of polyhydroquinoline as potent anti-diabetic and anti-glycating agents: Synthesis, in vitro α-amylase, α-glucosidase inhibition and anti-glycating activity with molecular docking insights DOI
Sajjad ur Rahman, Aftab Alam, Zahida Parveen

et al.

Bioorganic Chemistry, Journal Year: 2024, Volume and Issue: 150, P. 107501 - 107501

Published: May 31, 2024

Language: Английский

Citations

7
Non-targeted metabolomics and explainable artificial intelligence: Effects of processing and color on coniferyl aldehyde levels in Eucommiae cortex DOI

Yijing Pan,

Kehong Ming,

Dongmei Guo

et al.

Food Chemistry, Journal Year: 2024, Volume and Issue: 460, P. 140564 - 140564

Published: July 25, 2024

Language: Английский

Citations

5
Impact of very low carbohydrate ketogenic diets on cardiovascular risk factors among patients with type 2 diabetes; GRADE-assessed systematic review and meta-analysis of clinical trials DOI Creative Commons
Parisa Ghasemi,

Malihe Jafari,

Saber Jafari Maskouni

et al.

Nutrition & Metabolism, Journal Year: 2024, Volume and Issue: 21(1)

Published: July 19, 2024

Abstract Objective This study was designed to evaluate the impact of VLCKD on cardiovascular risk factors in patients with T2DM. Methods Until March 2024, extensive searches were conducted PubMed, Scopus, Web Science, Embase, and other relevant databases. The purpose identify clinical trials examining glycemic control, lipid profile, blood pressure. GRADE (Grading Recommendations Assessment, Development, Evaluation) method used assess evidence’s degree certainty. Results Our initial search found a total 2568 records finally 29 included final analysis. results showed that adherence from led significant reduction fasting sugar (WMD= -11.68 mg/dl; 95% CI: -18.79, -4.56; P = 0.001), HbA1c -0.29; -0.44, -0.14; < HOMA-IR(WMD= -0.71; -1.14, insulin -1.45; -2.54, -0.36; 0.009), triglyceride -17.95; -26.82, -9.07; systolic pressure -2.85, -4.99, 0.009) diastolic -1.40; -2.66, -0.13; 0.03). We also increase high-density lipoprotein (HDL) level after diet (WMD 3.93, 2.03, 5.84; 0.000). couldn’t find any differences between groups term LDL cholesterol levels. Conclusion People following experience more improvement when compared individuals control diets.

Language: Английский

Citations

4
DeepDRA: Drug repurposing using multi-omics data integration with autoencoders DOI Creative Commons
Taha Mohammadzadeh-Vardin, Amin Ghareyazi, Ali Gharizadeh

et al.

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(7), P. e0307649 - e0307649

Published: July 26, 2024

Cancer treatment has become one of the biggest challenges in world today. Different treatments are used against cancer; drug-based have shown better results. On other hand, designing new drugs for cancer is costly and time-consuming. Some computational methods, such as machine learning deep learning, been suggested to solve these using drug repurposing. Despite promise classical machine-learning methods repurposing predicting responses, deep-learning performed better. This study aims develop a model that predicts response based on multi-omics data, descriptors, fingerprints facilitates those responses. To reduce data's dimensionality, we use autoencoders. As multi-task model, autoencoders connected MLPs. We extensively tested our three primary datasets: GDSC, CTRP, CCLE determine its efficacy. In multiple experiments, consistently outperforms existing state-of-the-art methods. Compared models, achieves an impressive AUPRC 0.99. Furthermore, cross-dataset evaluation, where trained GDSC CCLE, it surpasses performance previous works, achieving 0.72. conclusion, presented current regarding generalization. Using this could assess responses explore repurposing, leading discovery novel drugs. Our highlights potential advanced advance therapeutic precision.

Language: Английский

Citations

4