Strong Binding of C-Glycosylic1,2-Thiodisaccharides to Galectin-3─Enthalpy-Driven Affinity Enhancement by Water-Mediated Hydrogen Bonds DOI
László Lázár, Anastasia S. Tsagkarakou, G.A. Stravodimos

et al.

Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 66(17), P. 12420 - 12431

Published: Sept. 2, 2023

Galectin-3 is involved in multiple pathways of many diseases, including cancer, fibrosis, and diabetes, it a validated pharmaceutical target for the development novel therapeutic agents to address unmet medical needs. Novel 1,2-thiodisaccharides with C-glycosylic functionality were synthesized by photoinitiated thiol-ene click reaction O-peracylated 1-C-substituted glycals 1-thio-glycopyranoses. Subsequent global deprotection yielded test compounds, which studied their binding human galectin-3 fluorescence polarization isothermal titration calorimetry show low micromolar Kd values. The best inhibitor displayed value 8.0 μM. An analysis thermodynamic parameters revealed that Gibbs free energy (ΔG) new inhibitors was dominated enthalpy (ΔH). mode four most efficient also X-ray crystallography uncovered unique role water-mediated hydrogen bonds conferring enthalpy-driven affinity enhancement inhibitors. This 1,2-thiodisaccharide-type scaffold represents lead discovery offers several possibilities further development.

Language: Английский

Targeting Myeloid Differentiation Primary Response Protein 88 (MyD88) and Galectin-3 to Develop Broad-Spectrum Host-Mediated Therapeutics against SARS-CoV-2 DOI Open Access
Kamal U. Saikh, Khairul Anam, Halima Sultana

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(15), P. 8421 - 8421

Published: Aug. 1, 2024

Nearly six million people worldwide have died from the coronavirus disease (COVID-19) outbreak caused by severe acute respiratory syndrome 2 (SARS-CoV-2) infection. Although COVID-19 vaccines are largely successful in reducing severity of and deaths, decline vaccine-induced immunity over time continuing emergence new viral variants or mutations underscore need for an alternative strategy developing broad-spectrum host-mediated therapeutics against SARS-CoV-2. A key feature is dysregulated innate immune signaling, culminating a high expression numerous pro-inflammatory cytokines chemokines lack antiviral interferons (IFNs), particularly type I (alpha beta) III (lambda). As natural host defense, myeloid differentiation primary response protein, MyD88, plays pivotal roles acquired responses via signal transduction pathways Toll-like receptors (TLRs), pathogen recognition (PRRs). However, recent studies highlighted that infection with viruses upregulates MyD88 impairs negatively regulating IFN. Galectin-3 (Gal3), another player infections, has been shown to modulate entry activating TLRs, NLRP3 inflammasome, NF-κB, resulting release contributing overall inflammatory response, so-called "cytokine storm". These suggest specific inhibition Gal3 could be promising therapy COVID-19. This review presents future directions MyD88- Gal3-targeted drug discovery, highlighting potential restore SARS-CoV-2 infections.

Language: Английский

Citations

5

Tapping into Metabolomics for Understanding Host and Rotavirus Group A Interactome DOI Creative Commons
Phiona Moloi Mametja,

Mmei Cheryl Motshudi,

Clarissa Marcelle Naidoo

et al.

Life, Journal Year: 2025, Volume and Issue: 15(5), P. 765 - 765

Published: May 10, 2025

Group A rotavirus continues to be a leading global etiological agent of severe gastroenteritis in young children under 5 years age. The replication this virus the host is associated with occurrence Lewis antigens and secretor condition. Moreover, histo-blood group (HBGAs) act as attachment factors outer viral protein VP4 for rotavirus. Therefore, study, we employed metabolomic approach reveal potential signature metabolic molecules pathways specific P[8] strain infection (VP4 genotype), which expression HBGA combined (Le) phenotypes, specifically secretor/Le(a+b+). Further integration achieved metabolomics results lipidomic proteomics metadata analyses was performed. Saliva samples were collected from diagnosed negative or positive total 22 that downregulated include butyrate, putrescine, lactic acid, 7 analytes. upregulated molecule 2,3-Butanediol. Significant pathway alterations also observed various metabolism processes, including galactose butanoate metabolisms. Butyrate played significant role revealed exhibit different reactions glycerolipids, glycerophospholipids, sphingolipids, sterol lipids, fatty acyls. butyrate might interact receptors free acid receptor 2 (FFAR2) 3 (FFAR3). provide fundamental insight into status monitoring its effects on humans.

Language: Английский

Citations

0

Investigation of Galectin-3 and Cardiotrophin-1 Concentrations as Biomarkers in Dogs with Neurological Distemper DOI Creative Commons
Alper Ertürk, Aliye Sağkan Öztürk, Atakan Öztürk

et al.

Veterinary Sciences, Journal Year: 2025, Volume and Issue: 12(5), P. 499 - 499

Published: May 20, 2025

Canine distemper, caused by Morbillivirus canis, is a highly morbid and lethal disease characterized multiple systemic neurological signs. In recent years, biomarkers, such as Galectin-3 Cardiotrophin-1, have been investigated in inflammatory degenerative diseases. However, the role of these biomarkers distemper has not investigated. The aim this study to compare blood serum Cardiotrophin-1 concentrations between control group, evaluate correlations with hematobiochemical parameters dogs distemper. Nineteen owned (13 diagnosed 6 controls) were included study. Hematobiochemical analyses performed all dogs, measured using ELISA. Serum markedly elevated compared group (p < 0.05). A negative correlation monocytes 0.05) positive platelet platelecrit levels observed. There was lymphocyte percentage 0.01) granulocyte 0.01). may serve for diagnosis understanding pathogenesis. Elevated indicate underlying neuroinflammation. This contribute pathogenesis

Language: Английский

Citations

0

Identification and functional characterization of galectin-3 in silver pomfret (Pampus argenteus) DOI

Suyang Chen,

Xionglin Li,

Kejing Huang

et al.

Aquaculture, Journal Year: 2024, Volume and Issue: 592, P. 741241 - 741241

Published: June 15, 2024

Language: Английский

Citations

2

Galectin-3’s Complex Interactions in Pancreatic Ductal Adenocarcinoma: From Cellular Signaling to Therapeutic Potential DOI Creative Commons
Milica Dimitrijevic Stojanovic, Bojan Stojanović, Ivan Radosavljević

et al.

Biomolecules, Journal Year: 2023, Volume and Issue: 13(10), P. 1500 - 1500

Published: Oct. 10, 2023

Galectin-3 (Gal-3) plays a multifaceted role in the development, progression, and prognosis of pancreatic ductal adenocarcinoma (PDAC). This review offers comprehensive examination its expression PDAC, interaction with various immune cells, signaling pathways, effects on apoptosis, therapeutic resistance. Additionally, prognostic significance serum levels Gal-3 is discussed, providing insights into potential utilization as biomarker. Critical analysis also extended to inhibitors their applications offering new avenues for targeted treatments. The intricate nature Gal-3’s PDAC reveals complex landscape that demands nuanced understanding interventions monitoring.

Language: Английский

Citations

5

Association between serum galectin-3 and chronic obstructive pulmonary disease: A meta-analysis DOI Creative Commons
Xiangyu Zhao, Bo Han,

Tang Wentao

et al.

Biomolecules and Biomedicine, Journal Year: 2024, Volume and Issue: 24(6), P. 1491 - 1500

Published: May 26, 2024

Chronic obstructive pulmonary disease (COPD) is a significant public health issue characterized by progressive and irreversible airflow limitation. The aim of this meta-analysis was to determine the association between changes in serum galectin-3 levels COPD assess relationship acute exacerbations (AECOPD). Relevant observational studies were retrieved from electronic databases, including PubMed, Web Science, Embase, Wanfang, China National Knowledge Infrastructure (CNKI). A random-effects model used combine data, incorporating influence between-study heterogeneity. Twelve case-control included. pooled results showed significantly higher level patients with compared controls (standardized mean difference [SMD] 0.60; 95% confidence interval [CI] 0.40 - 0.80; P < 0.001; I2 = 68%). Further suggested AECOPD those stable (SMD 0.33; CI 0.20 0.46; 0%). Subgroup analyses according age participants, proportion males, study quality scores did not change (P for subgroup differences all > 0.05). In conclusion, found have galectin-3, further elevated COPD.

Language: Английский

Citations

1

Increased Levels of Galectin-3 in Critical COVID-19 DOI Open Access

Ioanna Nikitopoulou,

Alice G. Vassiliou, Nikolaos Athanasiou

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(21), P. 15833 - 15833

Published: Oct. 31, 2023

Severe COVID-19 is related to hyperinflammation and multiple organ injury, including respiratory failure, thus requiring intensive care unit (ICU) admission. Galectin-3, a carbohydrate-binding protein exhibiting pleiotropic effects, has been previously recognized participate in inflammation, the immune response infections fibrosis. The aim of this study was evaluate relationship between galectin-3 clinical severity COVID-19, as well assess prognostic accuracy for probability ICU mortality. included 235 patients with active disease, treated two different Greek hospitals total. Our results showed that median serum levels on admission were significantly increased critical (7.2 ng/mL), compared less severe disease (2.9 ng/mL, p = 0.003). Galectin-3 non-survivors hospitalized higher than those survivors (median 9.1 ng/mL versus 5.8 0.001). mortality studied receiver operating characteristic (ROC) curve multivariate analysis further demonstrated concentration at hospital could be assumed an independent risk factor associated validated measurements second patient cohort from university hospital. results, apart strongly confirming advancing previous knowledge cohorts, explore possibility predicting mortality, which provide useful information clinicians. Therefore, seems establish its involvement prognosis patients, suggesting it serve promising biomarker COVID-19.

Language: Английский

Citations

3

The Role of Galectin-3 in Retinal Degeneration and Other Ocular Diseases: A Potential Novel Biomarker and Therapeutic Target DOI Open Access
Ziyi Zhou,

Zhaochen Feng,

Xiaojia Sun

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(21), P. 15516 - 15516

Published: Oct. 24, 2023

Galectin-3 is the most studied member of Galectin family, with a large range mediation in biological activities such as cell growth, proliferation, apoptosis, differentiation, adhesion, and tissue repair, well pathological processes inflammation, fibrosis, angiogenesis. As known to all, aberrant neovascularization are main pathophysiological retinal degeneration many ocular diseases. Therefore, review aims conclude role Gal3 various diseases occurrence development discuss its molecular mechanisms according research systemic At same time, we summarized predictive biomarker clinical application inhibitors possibility novel target for treatment

Language: Английский

Citations

2

Galectin-3 in Blood Serum and Lymphocytes as a Marker of Myocardial Damage in Patients with Arterial Hypertension and COVID-19 DOI
Nataliia Pokrovska,

Nataliia Denysenko,

Iryna Fomenko

et al.

Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 22(4), P. 250 - 260

Published: Dec. 1, 2023

Background:: The constant increase of arterial hypertension and the development pathology at an earlier age are global healthcare problems that cause damage to vital organs worsen patient prognosis. In recent years, studies have shown galectin-3 plays a role in progression coronavirus disease (COVID-19). Objective:: explanatory research study aimed analyze prognostic value de-termination serum blood lymphocytes patients with corona-virus Methods:: were divided into two groups: Group 1 consisted 36 individuals AH, 2 included 35 polysegmental COVID-19 pneumonia, 16 practically healthy control group. All underwent anthropometry, biochemical analysis, determination galectin-3, level lym-phocytes, IL-1β, IL-6, echocardiography. Results:: highest was found 1, while 2, concentration significantly decreased, mostly due treatment COVID-19, addition prolonged antihypertensive therapy. Conclusion:: higher both groups compared group (p<0.05). Arterial causes structural changes cardiovascular system associated elevated levels lymphocytes. It can be used as marker myocardial context hyper-tension COVID-19.

Language: Английский

Citations

1

Role of galectin-3 in enhancing HBV replication and predicting hepatocellular carcinoma: mechanistic insights and clinical implications DOI
Wei Jiang, Qingmin Zeng, Dongbo Wu

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 4, 2024

Abstract Background Hepatocellular carcinoma (HCC) is a common malignancy globally, often associated with hepatitis B virus (HBV) infection. Galectin-3 (Gal-3), multifunctional β-galactoside-binding protein, has been implicated in liver diseases. This study aimed to investigate the role of Gal-3 HBV replication and hepatic inflammation evaluate its potential as an early diagnostic biomarker for HCC. Methods An model was established HepG2 cells. The impact on DNA expressions HBsAg HBeAg were analyzed using quantitative PCR ELISA. Western blot analysis performed influence inflammatory signaling pathways. Serum levels patients various diseases measured by ELISA, their correlation markers evaluated. Results In HBV-replicating cells, overexpression significantly increased replication, HBsAg, expression, while knockdown had opposite effect. involved regulation pathway proteins, including NF-κB-p65, IL-1β, NLRP3, caspase-1. Analysis serum samples from revealed that elevated compared control group, there linear between expression clinical such ALT, AST, ALP. A incorporating WBC established, demonstrating superior predictive capability HCC AFP. Conclusion plays crucial are closely severity Moreover, shows promise detection Further research needed validate Gal-3's explore suitability therapeutic target.

Language: Английский

Citations

0