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Gentiopicroside attenuates lupus arthritis by targeting galectin-mediated macrophage activation.

BACKGROUND: Inflammatory arthritis represents a common and clinically challenging manifestation of systemic lupus erythematosus (SLE), with current therapeutic options often exhibiting limited efficacy. PURPOSE: This study aimed to investigate the anti-arthritic effects and underlying mechanism of gentiopicroside (GPS), a key bioactive constituent of the Jiawei Baihu Jia Guizhi Decoction (JBH), with a specific focus on its interaction with galectin-9-mediated pathways in macrophage activation. STUDY DESIGN: The anti-arthritic efficacy of GPS was investigated using a pristane-induced arthriti

Galectin-3 restrains T cell-driven inflammation in the testis and epididymis.

Galectin-3 (Gal-3) is a pleiotropic molecule involved in immune regulation and tissue homeostasis. While it has been implicated in reproductive tissue function, its role in shaping immune cell dynamics within the testis and epididymis remains incompletely defined. Here, we investigated the function of Gal-3 in the testis and epididymis under steady-state and inflammatory conditions, to determine its contribution to inflammatory responses and tissue damage. In both murine and human tissues, Gal-3 frequency and staining intensity increased along the testicular-epididymal axis, with the highest p

Whole-Blood Transcriptomics Highlights Galectin-1 in Systolic Blood Pressure.

BACKGROUND: Galectins regulate inflammation, fibrosis, immunity, and vascular remodeling. Although galectin-3 has been widely studied in cardiovascular disease, the relative contributions of other galectins to blood pressure regulation remain unclear. We systematically evaluated associations between galectin gene expression and systolic blood pressure (SBP) in African Americans. METHODS: Whole-blood mRNA sequencing data were analyzed from 419 African American participants in the GENE-FORECAST cohort who were free of type 2 diabetes and not receiving antihypertensive medications. LGALS1, LGALS…

Serum Galectin-3 as a biomarker in acute inflammatory polyradiculoneuropathies: a cohort study.

BACKGROUND AND AIMS: Guillain-Barré Syndrome (GBS) refers to a group of acute inflammatory polyradiculopathies characterized by a diffuse inflammatory attack on the peripheral nervous system, often triggered by a preceding infection. Despite significant progress in both diagnosis and treatment, only a few prognostic systems and useful biomarker have been proposed. In this study, we propose galectin-3 (Gal-3), a novel serum molecule identified expressed by Schwann cells and macrophages, as a potential biomarker with both prognostic and diagnostic significance in patients with GBS. METHODS: Ser

Extracellular Galectin-3/Carbohydrate Interactions Modulate Cancer Cellular Migration.

Galectin-3-mediated processes are important during many aspects of cancer progression, but they are not well understood. Galectin-3 is present extracellularly, and because of its carbohydrate recognition domain (CRD) and unstructured N-terminal domain (NTD), galectin-3 undergoes multimerization, which influences events such as carbohydrate-controlled cell-cell interactions. Investigations reported herein using an in vitro wound-healing assay show that exogenous galectin-3 inhibits cancer cellular migration. Since the addition of the galectin-3 CRD without the NTD does not arrest cellular migra

Association of Elevated Galectin-4 Concentrations with Obesity, Diabetes, and Cardiovascular Diseases.

Obesity, type 2 diabetes mellitus (T2DM), and cardiovascular diseases (CVDs) represent major global health burdens with overlapping pathophysiological mechanisms, including chronic low-grade inflammation, oxidative stress, and gut microbiota dysbiosis. Galectins, a family of β-galactoside-binding lectins, have been implicated in immune regulation, inflammation, and tissue remodeling. Among them, Galectin-4 (Gal-4), primarily expressed in the gastrointestinal tract, has emerged as a potential biomarker due to its roles in epithelial integrity, inflammatory signaling, and metabolic regulation. D…

Chlorogenic acid attenuates cardiac hypertrophy and fibrosis by downregulating galectin 3.

Chlorogenic acid, an ester of caffeic acid and quinic acid, is found in foods such as eggplant and peaches. Its role in heart disease remains poorly understood. This study investigated whether chlorogenic acid affects cardiac hypertrophy and fibrosis in animal and cellular models of isoproterenol-induced cardiac hypertrophy. Treatment of isoproterenol-stimulated cardiomyocytes with chlorogenic acid reduced cell size and the expression levels of cardiac hypertrophy-related genes. In the animal model, isoproterenol was delivered via an osmotic minipump for 2 weeks to induce cardiac hypertrophy,

Serum Galectin-1 as a Diagnostic Biomarker in Endometriosis: A Prospective Longitudinal Study.

Endometriosis is a chronic condition characterized by the presence of endometrial-like tissue outside the uterine cavity. It affects ~10% of reproductive-aged individuals and is associated with dysmenorrhea and infertility. Although imaging modalities have improved diagnosis, laparoscopy is required in many cases, contributing to 4-11 years of diagnostic delay. Non-invasive biomarkers could improve diagnosis and clinical decision-making, yet no candidate has achieved sufficient accuracy for routine use. Galectins, a family of β-galactoside-binding lectins involved in angiogenesis, immune regul…

Galectin-9 treatment is cytotoxic for B cell lymphoma by disrupting autophagy.

INTRODUCTION: The main cause of death for patients with non-Hodgkin lymphoma (NHL) remains therapy resistant relapses. Chemoresistance is commonly associated with apoptosis defects and upregulated autophagy. Therefore, novel therapeutic options that do not rely on apoptosis and target autophagy would be of interest to treat NHL. An agent that may fulfill these requirements is the glycan-binding protein Galectin-9 (Gal-9). METHODS: A panel of B cell lymphoma NHL cell lines, including diffuse large B cell lymphoma (DLBCL), mantle cell lymphoma (MCL), Burkitt's lymphoma (BL), and (chemoresistant

Galectin-8 deficiency promotes chronic splenomegaly persistence in Chagas disease.

Galectins (Gals) are mammalian lectins with affinity for β-galactosides, which drive the immune response through several mechanisms. The specific role of Gal-8 in the development of inflammation remains controversial, as it has been shown to induce either T cell proliferation or regulation in different models. During the acute phase of Trypanosoma cruzi infection, a characteristic splenomegaly is induced that is associated with both antigen-specific and non-specific polyclonal lymphocyte proliferation. This splenomegaly resolves as the infection transitions to the chronic phase. While the path…

Correlation Analysis of Genetic Mutations and Galectin Levels in Breast Cancer Patients.

Galectins are innate immune system regulators associated with disease progression in cancer. This paper aims to investigate the correlation between mutated cancer-critical genes and galectin levels in breast cancer patients to determine whether galectins and genetic profiles can be used as biomarkers for disease and potential therapy targets. Prisma Health Cancer Institute's Biorepository provided seventy-one breast cancer samples, including all four stages spanning the major molecular subtypes and histologies. Hotspot mutation statuses of cancer-critical genes were determined using multiplex …

Understanding the Role of Galectin-1 in Heart Failure: A Comprehensive Narrative Review.

Heart failure (HF) is the fastest-growing cardiovascular condition worldwide. The immune system may play a role in the development of HF since this condition is associated with elevated pro-inflammatory cytokine levels. HF is a life-threatening disease, and there is an increasing demand for diagnostic biomarkers, prognostic factors, and therapeutic agents that can help treat it. Galectin-1 (Gal-1) is the prototype galectin of the lectin family. Multiple signal transduction pathways are regulated by Ras proteins, which act as a molecular switch in cells. Gal-1 regulates T and B cell activation,

Serum Galectin-3 as a Non-Invasive Marker for Primary Sclerosing Cholangitis.

Primary sclerosing cholangitis (PSC) is a serious liver disease associated with inflammatory bowel disease (IBD). Galectin-3, an inflammatory and fibrotic molecule, has elevated circulating levels in patients with chronic liver disease and inflammatory bowel disease (IBD). This study aims to clarify whether galectin-3 can differentiate between patients with IBD, PSC, and PSC-IBD. Our study measured serum galectin-3 levels in 38 healthy controls, 55 patients with IBD, and 22 patients with PSC (11 patients had underlying IBD and 11 patients did not), alongside the urinary galectin-3 of these pat

Galectin-9 Mediates the Functions of Microglia in the Hypoxic Brain Tumor Microenvironment.

Galectin-9 (Gal-9) is a multifaceted regulator of various pathophysiologic processes that exerts positive or negative effects in a context-dependent manner. In this study, we elucidated the distinctive functional properties of Gal-9 on myeloid cells within the brain tumor microenvironment (TME). Gal-9-expressing cells were abundant at the hypoxic tumor edge in the tumor-bearing ipsilateral hemisphere compared with the contralateral hemisphere in an intracranial mouse brain tumor model. Gal-9 was highly expressed in microglia and macrophages in tumor-infiltrating cells. In primary glia, both th

Galectin-9 - ligand axis: an emerging therapeutic target for multiple myeloma.

Galectin-9 (Gal-9) is a tandem-repeat galectin with diverse roles in immune homeostasis, inflammation, malignancy, and autoimmune diseases. In cancer, Gal-9 displays variable expression patterns across different tumor types. Its interactions with multiple binding partners, both intracellularly and extracellularly, influence key cellular processes, including immune cell modulation and tumor microenvironment dynamics. Notably, Gal-9 binding to cell-specific glycoconjugate ligands has been implicated in both promoting and suppressing tumor progression. Here, we provide insights into Gal-9 and its

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… These groups include proto-type galectins (galectin (Gal)-1, -2, -5, -7, -10, -11, -13, -14, and -15), characterized by a single carbohydrate-recognition domain (CRD) that can form homodimers; chimera-type galectins (Gal-3), featuring a single CRD and an amino-terminal polypeptide tail rich in proline … Carbohydrate-recognition domains of galectin-9 are involved in intermolecular interaction with galectin-9 itself and other members of the galectin family . Glycobiology . ( 2007 ) 17 : 423–32 . doi: 10.1093/glycob/cwm001 17223646 61 Vaitaitis GM Wagner DH Jr . …

Galectin-1 Modulates the Fusogenic Activity of Placental Endogenous Retroviral Envelopes.

Syncytin-1 and -2 are glycoproteins encoded by human endogenous retrovirus (hERV) that, through their fusogenic properties, are needed for the formation of the placental syncytiotrophoblast. Previous studies suggested that these proteins, in addition to the EnvP(b) envelope protein, are also involved in other cell fusion events. Since galectin-1 is a β-galactoside-binding protein associated with cytotrophoblast fusion during placental development, we previously tested its effect on Syncytin-mediated cell fusion and showed that this protein differently modulates the fusogenic potential of Syncy

Suppression of local inflammation via galectin-anchored indoleamine 2,3-dioxygenase.

The treatment of chronic inflammation with systemically administered anti-inflammatory treatments is associated with moderate-to-severe side effects, and the efficacy of locally administered drugs is short-lived. Here we show that inflammation can be locally suppressed by a fusion protein of the immunosuppressive enzyme indoleamine 2,3-dioxygenase 1 (IDO) and galectin-3 (Gal3). Gal3 anchors IDO to tissue, limiting the diffusion of IDO-Gal3 away from the injection site. In rodent models of endotoxin-induced inflammation, psoriasis, periodontal disease and osteoarthritis, the fusion protein rema

Galectin-1 Used in Assisted Reproduction-Embryo Safety and Toxicology Studies.

Galectin-1 has been cited as a mediator involved in preventing early embryonic death in mammals and is implicated in maternal-fetal tolerance. Galectin-1 is also a reasonable tool to improve fertility in assisted reproduction procedures. As recommended in the ICH guidelines (S5-R2 and S6-R1) and based on bioethical concerns, we chose bovine embryos (BE) to assess in vitro embryo development as part of a larger reproductive safety and toxicology study in progress. The design considered in vitro embryo development using rHGAL-1 supplementations (in three different concentrations) of the in vitro

Galectin-1: A Traditionally Immunosuppressive Protein Displays Context-Dependent Capacities.

Galectin-Carbohydrate interactions are indispensable to pathogen recognition and immune response. Galectin-1, a ubiquitously expressed 14-kDa protein with an evolutionarily conserved β-galactoside binding site, translates glycoconjugate recognition into function. That galectin-1 is demonstrated to induce T cell apoptosis has led to substantial attention to the immunosuppressive properties of this protein, such as inducing naive immune cells to suppressive phenotypes, promoting recruitment of immunosuppressing cells as well as impairing functions of cytotoxic leukocytes. However, only in recent

Antibody-mediated neutralization of galectin-3 as a strategy for the treatment of systemic sclerosis.

Systemic sclerosis (SSc) is an autoimmune, inflammatory and fibrotic disease with limited treatment options. Developing new therapies is therefore crucial to address patient needs. To this end, we focused on galectin-3 (Gal-3), a lectin known to be associated with several pathological processes seen in SSc. Using RNA sequencing of whole-blood samples in a cross-sectional cohort of 249 patients with SSc, Gal-3 and its interactants defined a strong transcriptomic fingerprint associated with disease severity, pulmonary and cardiac malfunctions, neutrophilia and lymphopenia. We developed new Gal-3