Ultraviolet light (UV) can cause serious damage to human skin. The inflammatory reaction arising from repeated UV exposure leads to severe skin lesions and even promotes photo-carcinogenesis. Iron overload is featured by excessive iron intake and deposition and will promote inflammatory response inside cells. However, the core molecules involved in UV radiation induced iron overload and related anti-inflammatory strategies remain unclear. Signature genes involved in UV-irradiated skin were filtered through integrated datasets from the Gene Expression Omnibus (GEO) database. Subsequently, immune cell infiltration analysis was carried out to examine the relationship between signature gene expression and immune cell abundance. Single cell RNA-seq matrix data implicated in UV-irradiated skin was then applied to assess the expression level of signature genes in different cell clusters and to find out the core cell type and the key signaling pathway involved in UV radiation. Finally, cytological and animal experiments were conducted to investigate the potential of signature genes as therapeutic targets. SAT1 and RBMS1 were screened and validated as signature genes of UV irradiation. Immune cell infiltration analysis demonstrated that SAT1 and RBMS1 expression were associated closely with immune cell abundance, and skin fibroblasts were identified as the central cell type to communicate with other cell clusters in UV-irradiated skin. Disturbance of SAT1 exerted observably more suppressive effects on the release of inflammatory cytokines than overexpression of RBMS1. Two small molecule drugs targeting SAT1, namely Argatroban and Menadione, were predicted. Moreover, their therapeutic potentials in the treatment of UV-irradiated skin injury were confirmed experimentally.

The objective of this study is to develop a predictive model combining multiple indicators to quantify the risk of mild cognitive impairment (MCI) in T2DM patients.

This study included Chinese T2DM patients who were hospitalized at Zhongda Hospital between November 2021 and May 2023. Clinical data, including demographics, medical history, biochemical tests, and cognitive status, were collected. Cognitive assessment was performed using neuropsychological tests, and MCI was diagnosed based on the Montreal Cognitive Assessment (MoCA) scores. The dataset was randomly divided into a training set and a validation set in a 7:3 ratio. Logistic regression analysis was conducted to identify factors influencing MCI in the training set. A nomogram-based scoring model was then developed by integrating these findings with high-risk clinical variables, and its performance was validated in the validation set.

In this study, T2DM patients were divided into a training set and a validation set in a 7:3 ratio. There were no significant differences in MCI incidence, demographics, or clinical characteristics between the two groups, confirming the appropriateness of model construction. In the training set, Galectin-3 and CVAI were significantly negatively correlated with cognitive function (MoCA and MMSE scores), and this negative correlation remained after adjusting for confounding variables. Logistic regression analysis revealed that age, CVAI, and Galectin-3 significantly increased the risk of MCI, while years of education had a protective effect. The constructed nomogram model, which integrated age, sex, education level, hypertension, CVAI, and Galectin-3 levels, exhibited high predictive performance (C-index of 0.816), with AUCs of 0.816 in the training set and 0.858 in the validation set, outperforming single indicators. PR curve analysis further validated the superiority of the nomogram model.

The straightforward, highly accurate, and interactive nomogram model developed in this study facilitate the early risk prediction of MCI in individuals with T2DM by incorporating Galectin-3, CVAI, and other common clinical risk factors.

Galectin-9 (Gal-9) has gained increasing attention in recent years in the field of cancer immunology. Its interactions with various immune cell types in the tumor microenvironment influence tumor progression, making it a novel target for immunotherapy. Despite its potential as a therapeutic target, the prognostic significance of Gal-9 in tumor cells remains unclear. Conflicting data exists on its expression levels and outcomes, prompting a comprehensive review and meta-analysis to elucidate its independent prognostic role across different cancer types. This study aims to examine the varying effects of Gal-9 expression across various cancer subtypes, providing insights into its potential as a prognostic marker and highlighting its significance in the realm of cancer treatment. To assess the prognostic significance of Gal-9 expression in cancer, we conducted a comprehensive database search across PubMed, Embase, and Web of Science, incorporating studies published until December 2024, regardless of language. Using pooled hazard ratios (HRs) with 95% confidence intervals (CIs), we evaluated the role of Gal-9 expression in predicting cancer outcomes across various cancer types. Our analysis encompassed 29 studies with a total of 4,720 patients to investigate the prognostic significance of Gal-9 expression across different cancer types. The results demonstrated that elevated Gal-9 expression was significantly associated with improved overall survival (OS) in solid tumors, with a pooled hazard ratio of 0.75 (95% CI: 0.63-0.90, p =  0.002). No statistically significant correlation was observed between Gal-9 expression and cancer recurrence (HR =  0.88, 95% CI: 0.65-1.19, p =  0.42). Conversely, in hematological cancers, high Gal-9 expression correlated with more rapid disease progression, as reflected by progression-free survival (PFS) or time to treatment (TTT) (HR =  2.29, 95% CI: 1.26-4.16, p =  0.007). The subgroup analyses further revealed that higher Gal-9 expression was associated with OS in gastrointestinal and urological cancers and was linked to disease-free survival (DFS) and recurrence-free survival (RFS) in hepatobiliary and urological cancers. Our research has uncovered that Gal-9 serves as a promising prognostic indicator for solid tumors, offering valuable insights into patient outcomes. High levels of Gal-9 expression within gastrointestinal, hepatobiliary, and urological cancers have been linked to better prognoses, while its presence in hematological cancers is associated with poorer outcomes. These contrasting findings emphasize the importance of interpreting biomarkers with careful consideration to the specific context. Moreover, our study sheds light on the diverse physiological roles of intracellular and secreted Gal-9, highlighting the intricate ways in which this protein influences cancer progression.

Galectins play pivotal roles in cellular recognition and signaling processes by interacting with glycoconjugates. Extensive research has highlighted the significance of Galectins in the context of cancer, aiding in the identification of biomarkers for early detection, personalized therapy, and predicting treatment responses. This review offers a comprehensive overview of the structural characteristics, ligand-binding properties, and interacting proteins of Galectins. We delve into their biological functions and examine their roles across various cancer types. Galectins, characterized by a conserved carbohydrate recognition domain (CRD), are divided into prototype, tandem-repeat, and chimera types based on their structural configurations. Prototype Galectins contain a single CRD, tandem-repeat Galectins contain two distinct CRDs linked by a peptide, and the chimera-type Galectin-3 features a unique structural arrangement. The capacity of Galectins to engage in multivalent interactions allows them to regulate a variety of signaling pathways, thereby affecting cell fate and function. In cancer, Galectins contribute to tumor cell transformation, angiogenesis, immune evasion, and metastasis, making them critical targets for therapeutic intervention. This review discusses the multifaceted roles of Galectins in cancer progression and explores current advancements in the development of Galectin-targeted therapies. We also address the challenges and future directions for integrating Galectin research into clinical practice to enhance cancer treatment outcomes. In brief, understanding the complex functions of Galectins in cancer biology opens new avenues for therapeutic strategies. Continued research on Galectin interactions and their pathological roles is essential for developing effective carbohydrate-based treatments and improving clinical interventions for cancer patients.

Galectins are expressed by different immune and nonimmune cells with diverse immunomodulatory properties. However, their roles in erythropoiesis remain unknown. We investigated the expression of galectin genes in splenic CD71+ erythroid cells (CECs) from neonatal BALB/c mice at various developmental stages using bulk RNA sequencing. Our analysis revealed distinct gene expression profiles at different ages. Specifically, CECs from day-3 mice had a markedly different expression pattern compared to those from days 6, 12, and 28. Notably, Lgals1, Lgals3, Lgals4, Lgals8, and Lgals9 were constitutively expressed in CECs, with galectin-3 (Gal-3) showing predominant surface expression, unlike Gal-1 and Gal-9. Further analysis revealed that Gal-3+ CECs exhibited elevated levels of TGF-β, ROS, arginase I, VISTA, and PD-L1, correlating with enhanced immunosuppressive functions. These cells also demonstrated increased CD45, c-kit, Ki67, and p21 levels, indicating heightened proliferative activity despite showing increased apoptosis. Moreover, we found that Gal-3+ CECs displayed enhanced activation of signaling pathways, including STAT5, MAPK, and LCK. Additionally, Gal-3+ CECs co-expressed Fas and FasL, implicating these molecules in the regulation of early erythroblasts. Notably, Gal-3 interacted with CD71 and GARP, influencing CECs' immunoregulatory roles. In tissue-specific studies, we found varying frequencies of Gal-3+ CECs across the spleen, liver, and bone marrow (BM), with notable variations in the placenta and fetal liver. These results were paralleled in human BM-derived CECs, which also exhibited high Gal-3 levels. Our findings emphasize the critical role of Gal-3 in modulating erythropoiesis and suggest that Gal-3+ CECs possess enhanced immunoregulatory capacities.

Galectin-9 is overexpressed in a variety of cancers and associated with worse clinical outcome in some cancers. However, the regulators driving Galectin-9 expression are unknown. Here, we defined the transcriptional regulators and epigenetic circuitry of Galectin-9 in pediatric T cell acute lymphoblastic leukemia (T-ALL), as an example of a disease with strong Galectin-9 expression, in which higher expression was associated with lower overall survival. By performing a genome-wide CRISPR screen, we identified the transcription factors IRF1 and TFAP4 as key regulators for Galectin-9 expression by binding its regulatory elements. Whereas IRF1 was observed exclusively on the promoter, TFAP4 binding was detected at an enhancer solely in T-ALL cells associated with higher Galectin-9 levels. Together, our results show that IRF1 is responsible and indispensable for Galectin-9 expression and TFAP4 further fine-tunes its expression. Our approach, a flow-based genome-wide CRISPR screen complemented by transcription factor binding and enhancer mapping, creates innovative opportunities for understanding and manipulating epigenetic transcriptional regulation in cancer.

The inherent carbohydrate-binding specificities of human galectins can serve as recognition elements in both biotechnological and biomedical applications. The combination of the carbohydrate-recognition domain (CRD) of galectins fused to peptides or proteins for purification, immobilization, and imaging enables multifunctional utilization within a single protein. We present here a library of color-coded galectin fusion proteins that incorporate a His6-tag, a fluorescent protein, and a SpyCatcher or SpyTag unit to enable immobilization procedures. These galectin fusion proteins exhibit similar binding properties to the non-fused galectins with micromolar apparent binding affinities. N- and C-terminal fusion partners do not interfere with the SpyCatcher/SpyTag immobilization. By applying SpyCatcher/SpyTag-mediated SC-ST-Gal-3 conjugates, we show the stepwise formation of a three-layer ECM-like structure in vitro. Additionally, we demonstrate the SpyCatcher/SpyTag-mediated immobilization of galectins in microgels, which can serve as a transport platform for localized targeting applications. The proof of concept is provided by the galectin-mediated binding of microgels to colorectal cancer cells.

Protein self-assembly into a crystal in vivo triggers acute or chronic organ injury that can lead to intractable diseases lacking specific treatment options. In this study, we report the discovery of ionic arginine-rich peptides to disrupt the pathogenic galectin-10 (gal-10) crystallization, where the aberrant deposition of gal-10 crystals in airways causes the activation of IL-1β-dependent inflammation and the stimulation of epithelial cells to produce TNF-α. Gal-10 crystals show susceptibility to pH changes and charged residue substitutions at the protein packing interfaces, manifesting the role of charge-charge attractions across protein-protein interaction interfaces in governing gal-10 crystallization. To dissolve the gal-10 crystal, the ionic peptides R9 and R12Y8 were identified to eliminate the interprotein charge-charge interactions. The efficacy of R12Y8 in mitigating the gal-10 crystallopathy in vivo was assessed in a crystal-induced lung inflammation mice model. The mice intratracheally administrated by R12Y8 exhibited a downregulated release of proinflammatory cytokines and reduced infiltration of inflammatory cells in the lungs. Our study demonstrates that the pathogenic gal-10 crystallization is readily eliminated by R-rich peptides, which may display translational potentials for the treatment of gal-10 crystallopathy.

The accumulation of amyloid-β (Aβ) and overactivation of microglia contribute to the pathogenesis of Alzheimer's disease (AD), but the interaction between microglial activation and Aβ deposition in AD remains elusive. Here we revealed that Aβ activates microglia and promotes the release of Galectin-9 (Gal-9), a member of the β-galactoside-binding family of lectins. The levels of Gal-9 in the cerebrospinal fluid and brain tissues of AD patients are higher than those in control subjects. Gal-9 interacts with Aβ and promotes its aggregation, generating Gal-9-Aβ fibrils with enhanced seeding activity and neurotoxicity. The expression of Gal-9 increases with age in the brains of APP/PS1 transgenic mice. Knockout of Gal-9 in APP/PS1 mice substantially reduced Aβ sedimentation, neuroinflammation, and cognitive impairment. Moreover, depletion of Gal-9 inhibited the seeding activity of brain homogenates from APP/PS1 mice. These findings reveal a mechanism by which microglia-derived Gal-9 accelerates Aβ aggregation and seeding in AD. Thus, strategies aimed at inhibiting Gal-9 may hold promise as a disease-modifying therapy to alleviate AD pathology.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, characterized by an extremely poor prognosis and limited therapeutic options. Central to the progression and immune evasion of PDAC is the tumor (immune) microenvironment (TIME), where immune checkpoint proteins such as galectin-9 (Gal-9) play pivotal roles. Gal-9 significantly contributes to the immunosuppressive milieu of PDAC by interacting with various immune cells, such as T cells, macrophages, and myeloid-derived suppressor cells (MDSCs). These interactions suppress anti-tumor immunity, thus facilitating tumor growth and metastasis. This review comprehensively examines the multifaceted role of Gal-9 in the TIME of PDAC, detailing its mechanisms of action, including the induction of regulatory T cells, polarization of tumor-associated macrophages, and modulation of apoptotic pathways via Tim-3 and caspase activation. The therapeutic potential of targeting Gal-9, either alone or in combination with other immune checkpoint inhibitors such as anti-PD-L1, is also discussed, highlighting preclinical findings that suggest promising avenues for enhancing anti-tumor immune responses. By elucidating the complex biological activities of Gal-9 and its interactions within the TIME, this review underscores the importance of innovative therapeutic strategies aimed at mitigating the immunosuppressive effects of Gal-9 in PDAC.

Galectins are widely distributed throughout the animal kingdom, from marine sponges to mammals. Galectins are a family of soluble lectins that specifically recognize β-galactoside-containing glycans and are categorized into three subgroups based on the number and function of their carbohydrate recognition domains (CRDs). The interaction of galectins with specific ligands mediates a wide range of biological activities, depending on the cell type, tissue context, expression levels of individual galectin, and receptor involvement. Galectins affect various immune cell processes through both intracellular and extracellular mechanisms and play roles in processes, such as apoptosis, angiogenesis, and fibrosis. Their importance has increased in recent years because they are recognized as biomarkers, therapeutic agents, and drug targets, with many other applications in conditions such as cardiovascular diseases and cancer. However, little is known about the involvement of galectins in liver diseases. Here, we review the functions of various galectins and evaluate their roles in liver diseases.

PRDX2 is significantly expressed in various cancers and is associated with the proliferation of tumor cells. Nonetheless, the precise mechanism of PRDX2 in tumor immunity remains incompletely understood. This study aims to investigate the impact of PRDX2, which is highly expressed in lung adenocarcinoma, on T cells in the tumor immune microenvironment, and its immune action target to promote the immune escape of lung cancer cells, to provide a theoretical basis for lung adenocarcinoma treatment with PRDX2 as the target.

Mouse animal models to verify the effect of Conoidin A treatment on tumor growth and T cell infiltration. Flow cytometry and Western blot verified tumor cell apoptosis in the in vitro co-culture system as well as granzyme B and perforin expression in T cells. RNA-Seq was used to obtain the downstream immune molecule. si-RNA knockdown of Galectin-9 was co-cultured with T cells in vitro. Immunofluorescence and Western blot verified that PRDX2 regulates Galectin-9 expression through HDAC3.

PRDX2 expression was negatively correlated with CD8+ T cell expression in LUAD patients. Inhibition of PRDX2 significantly enhanced T-cell killing of LUAD cells and reduced tumor load in both in vitro and in vivo models. Mechanistically, Conoidin A or shRNA_PRDX2 decreased Galectin-9 expression by down-regulating the phosphorylation of HDAC3, consequently enhancing the infiltration and function of CD8+ T cells.

This study reveals the role of the PRDX2/HDAC3/Galectin-9 axis in LUAD immune escape and indicates Galectin-9 as a promising target for immunotherapy.

Endothelial dysfunction can lead to various harmful cardiovascular complications. The importance of galectin-3 (Gal-3) has been proposed in some cardiac diseases related to chronic inflammation. However, its role in hypertension-induced endothelial dysfunction remains unclear.

We enrolled 120 patients with hypertension, assessed their baseline characteristics, and monitored their 7-year cardiovascular outcomes. We performed an enzyme-linked immunosorbent assay to measure serum Gal-3 levels. The vascular reactivity index (VRI) was examined by digital thermal monitoring. Patients with VRI <1.0, 1.0 to <2.0, and ≥2.0 were defined as having poor, intermediate, and good vascular reactivity, respectively.

Among the recruited patients, 12 had poor vascular reactivity, 57 had intermediate vascular reactivity, and 51 had good vascular reactivity. Older age, higher total cholesterol levels, higher low-density lipoprotein cholesterol levels, lower estimated glomerular filtration rate, and higher Gal-3 levels were associated with poor endothelial dysfunction. Multivariate linear regression analysis showed that age and Gal-3 levels were correlated with VRI. During the 7-year follow-up period, patients with higher Gal-3 levels had more cardiovascular events.

Higher Gal-3 levels are associated with endothelial dysfunction and unfavorable cardiovascular outcomes in patients with hypertension, suggesting its potential role in the hypertension-induced endothelial dysfunction.

Idiopathic granulomatous mastitis (IGM) is a chronic inflammatory disorder characterised by the formation of non-caseating granulomas in breast tissue, primarily affecting young women of childbearing age. The aetiology of IGM remains unclear, with potential factors including trauma, hormonal influences, and autoimmune responses. Recent studies suggest that immune dysregulation may play a critical role in IGM, highlighting the need for exploration of biomarkers involved in inflammation and immune modulation, particularly LL-37, galectin-3, IL-36, and TLR3.

This study included 36 patients diagnosed with IGM and 37 healthy controls. Blood samples were collected from all participants, and serum levels of LL-37, IL-36α, galectin-3, and TLR3 were analyzed using enzyme-linked immunosorbent assay (ELISA). Immunohistochemical evaluations were conducted on breast tissue samples from 16 IGM patients and 10 controls who underwent mammoplasty. Clinical data, including laboratory tests and imaging results, were also collected and analyzed. Statistical analyses were performed using the IBM-SPSS-22.0 software, with significance set at p < 0.05.

Serum levels of LL-37, IL-36α, galectin-3, and TLR3 were significantly lower in IGM patients compared to healthy controls (p < 0.001 for all). Immunohistochemical analysis revealed reduced expression of LL-37 in IGM tissue samples, while galectin-3 levels were comparable between the IGM and control groups (p = 0.32). Clinical evaluations indicated significant improvements in inflammatory markers (CRP and ESR) and mass size over the treatment period.

The findings of this study suggest that LL-37, IL-36α, galectin-3, and TLR3 are implicated in the pathogenesis of IGM, with their serum levels being significantly diminished in affected patients. The observed reduction in LL-37 may contribute to the decline in IL-36α and TLR3 levels, indicating a potential role of these biomarkers in the inflammatory processes associated with IGM. Further research is warranted to elucidate the mechanisms underlying these alterations and their implications for the diagnosis and treatment of IGM.

Transfusion-dependent beta thalassemia (TDT) is a genetic disorder characterized by low haemoglobin levels, often leading to myocardial iron overload (MIO) and myocardial fibrosis (MF). Cardiac Magnetic Resonance (CMR) represents the gold standard for MIO and MF assessment, although its limited availability and high costs pose challenges. Left Ventricular Global Longitudinal Strain (LV GLS) measured by Speckle Tracking Echocardiography (STE) could offer a valuable alternative.

A monocentric diagnostic accuracy study was conducted to compare the performance of LV GLS with CMR using T2* for evaluating MIO and late gadolinium enhancement (LGE) for detecting MF. Between January 2022 and January 2023, 44 consecutive patients with TDT were enrolled. For each participant was performed LV GLS with STE, including CMR with T2* technique and LGE sequences.

CMR identified MIO in 8 patients (18 %) and MF in 5 (11 %). LV GLS STE was normal in patients without MIO (-20.6 ± 3.1 %) or MF (-20.6 ± 2.8 %), significantly differing from those with MIO (-18.2 ± 2.1 %, p = 0.043) and MF (-16.4 ± 1.7 %, p = 0.002). ROC analysis indicated an optimal LV GLS STE cutoff of -19.8 % for MIO (AUC = 0.76, 95 % CI: 0.59-0.93, p = 0.054) with an overall diagnostic accuracy of 64 % and an optimal cutoff of -18.3 % for MF (AUC = 0.93, 95 % CI: 0.85-1.00, p = 0.009) with an accuracy of 86 %.

The findings of this pilot study indicate that LV GLS with STE, may be a cost-effective screening tool for the early detection of MIO and MF in TDT patients.

Optimizations are expected in the development of immunotherapy for the treatment of Triple-negative breast cancer (TNBC). We studied the expression of galectin-9 (Gal-9) after irradiation and assessed the differential impacts of its targeting with or without radiotherapy. Tumor resections from TNBC patients who received neoadjuvant radiotherapy revealed higher levels of Gal-9 in comparison to their baseline level, only in non-responder patients. Gal-9 expression was also found to be increased in TNBC tumor biopsies and cell lines after irradiation. We investigated the therapeutic advantage of targeting Gal-9 after radiotherapy in mice. Irradiated 4T1 cells or control non-irradiated 4T1 cells were injected into BALB/c mice. Anti-Gal-9 antibody treatment decreased tumor progression only in mice injected with irradiated 4T1 cells. This proof-of-concept study demonstrates that Gal-9 could be considered as a dynamic biomarker after radiotherapy for TNBC and suggests that Gal-9 induced-overexpression could represent an opportunity to develop new therapeutic strategies for TNBC patients.

Galectin-3 (Gal-3) is a pro-fibrotic β-galactoside binding lectin highly expressed in fibrotic liver and implicated in hepatic fibrosis. GB1107 is a novel orally active Gal-3 small molecule inhibitor that has high affinity for Gal-3 >1000-fold selectively over other galectins. The aim of this study was to characterise GB1107 and galectin-3 in vitro and in vivo in the context of fibrosis signalling and liver disease.

Liver fibrosis was induced by administration of CCl4 twice weekly by intraperitoneal injection in mice for 8 weeks. GB1107 was orally administered once daily (10 mg/kg) for the last 4 weeks of CCl4 treatment. Fibrosis was assessed by picrosirius red staining of FFPE sections. Liver enzymes, Gal-3 and downstream biomarkers were assessed in liver and plasma. Paired-end sequencing was performed on the Nextseq 2000 platform. Pathway enrichment analysis was performed to determine enrichment of differentially expressed genes (DEGs) within Reactome pathways and Gene Ontology (GO) terms.

GB1107 significantly reduced plasma transaminases and liver Gal-3 and reduced liver fibrosis. RNAseq analysis of whole liver showed that 1659 DEGs were identified with CCl4 treatment compared to control. Pathways enriched in up-regulated genes in the CCl4 group included those related to the extracellular matrix, collagen biosynthesis and assembly, cell cycle and the immune system. Comparing GB1107 treatment with CCl4 control 1147 DEGs were identified. GB1107 effectively reversed the majority of the CCl4 induced gene changes.

GB1107 attenuated liver fibrosis and highlights Gal-3 as a therapeutic target for hepatic fibrosis.

The Astragalus mongholicus Bunge and Panax notoginseng formula (A&P) has been clinically shown to effectively slow down the progression of chronic kidney disease (CKD) and has demonstrated significant anti-fibrosis effects in experimental CKD model. However, the specific active ingredients and underlying mechanism are still unclear. The active ingredients of A&P were analyzed by Ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-HR-MS). A mouse model of CKD was constructed by 5/6 nephrectomy. Renal function was assessed by creatinine and urea nitrogen. Real-time PCR and Western Blot were performed to detect the mRNA and protein changes in kidney and cells. An in vitro fibrotic cell model was constructed by TGF-β induction in TCMK-1 cells. The results showed that thirteen active ingredients of A&P were identified by UPLC-HR-MS, nine of which were identified by analysis with standards, among which the relative percentage of NOB was high. We found that NOB treatment significantly improved renal function, pathological damage and reduced the expression level of fibrotic factors in CKD mice. The results also demonstrated that Lgals1 was overexpressed in the interstitial kidney of CKD mice, and NOB treatment significantly reduced its expression level, while inhibiting PI3K and AKT phosphorylation. Interestingly, overexpression of Lgals1 significantly increased fibrosis in TCMK1 cells and upregulated the activity of PI3K and AKT, which were strongly inhibited by NOB treatment. NOB is one of the main active components of A&P. The molecular mechanism by which NOB ameliorates renal fibrosis in CKD may be through the inhibition of Lgals1/PI3K/AKT signaling pathway.

Gestational diabetes mellitus (GDM) represents a significant metabolic disorder that affects pregnant women worldwide and has negative consequences for both the mother and her offspring. This research aims to investigate the relation between circulating levels of Galectin-3 and the incidence of GDM, and to evaluate its potential as a biomarker for monitoring and early detection of the disease.

A thorough search of the literature has been performed using databases such as Scopus, Web of science, Embase, Cochrane Library and PubMed. The standardized mean difference (SMD) and corresponding confidence intervals (CIs) were used to compute the effect size from individual records and pooled using the Random-effect model.

Our meta-analysis synthesized data from 9 studies, encompassing 1,286 participants (533 GDM patients and 753 healthy pregnant controls). The findings demonstrated a considerable increase in Galectin-3 levels among individuals diagnosed with GDM as compared to the healthy control (SMD = 0.929; CI: 0.179-1.679; p = 0.015), with observed heterogeneity (I2 = 87%; p < 0.001). Subgroup analyses revealed the influence of factors such as age, BMI, study design, and sample type on Galectin-3 levels. A meta-regression analysis further identified trends indicating that levels of Galectin-3 are linked to gestational age, specific geographical areas, and sample size.

Increased levels of Galectin-3 exhibit a significant association with GDM, indicating its prospective utility as a biomarker for early detection and risk assessment. Further research is warranted to elucidate its regulation and clinical implications in GDM management.

The online version contains supplementary material available at 10.1007/s40200-024-01461-z.

This review explores some of the complex mechanisms underlying antitumor T-cell response, with a specific focus on the balance and cross-talk between selected co-stimulatory and inhibitory pathways. The tumor microenvironment (TME) fosters both T-cell activation and exhaustion, a dual role influenced by the local presence of inhibitory immune checkpoints (ICs), which are exploited by cancer cells to evade immune surveillance. Recent advancements in IC blockade (ICB) therapies have transformed cancer treatment. However, only a fraction of patients respond favorably, highlighting the need for predictive biomarkers and combination therapies to overcome ICB resistance. A crucial aspect is represented by the complexity of the TME, which encompasses diverse cell types that either enhance or suppress immune responses. This review underscores the importance of identifying the most critical cross-talk between inhibitory and co-stimulatory molecules for developing approaches tailored to patient-specific molecular and immune profiles to maximize the therapeutic efficacy of IC inhibitors and enhance clinical outcomes.

Cellular mesenchymal-epithelial transition factor (c-MET), also known as hepatocyte growth factor receptor (HGFR), is a crucial receptor tyrosine kinase implicated in various solid tumors, including lung, breast, and liver cancers. The concomitant expression of c-MET and PD-L1 in tumors, such as hepatocellular carcinoma, highlights their prognostic significance and connection to therapeutic resistance. Cancer-associated fibroblasts and mesenchymal stromal cells produce hepatocyte growth factor (HGF), activating c-MET signaling in tumor cells and myeloid-derived suppressor cells (MDSC). This activation leads to metabolic reprogramming and increased activity of enzymes like glutaminase (GLS), indoleamine 2,3-dioxygenase (IDO), and arginase 1 (ARG1), depleting essential amino acids in the tumor microenvironment that are vital for effector immune cell function. This review highlights the interplay between tumor cells and myeloid-derived suppressor cells (MDSCs) that create an immunosuppressive environment while providing targets for c-MET-focused immunotherapy. It emphasizes the clinical implications of c-MET inhibition on the behavior of immune cells such as neutrophils, macrophages, T cells, and NK cells. It explores the potential of c-MET antagonism combined with immunotherapeutic strategies to enhance cancer treatment paradigms. This review also discusses the innovative cancer immunotherapies targeting c-MET, including chimeric antigen receptor (CAR) therapies, monoclonal antibodies, and antibody-drug conjugates, while encouraging the development of a comprehensive strategy that simultaneously tackles immune evasion and enhances anti-tumor efficacy further to improve the clinical prognoses for patients with c-MET-positive malignancies. Despite the challenges and variability in efficacy across different cancer subtypes, continued research into the molecular mechanisms and the development of innovative therapeutic strategies will be crucial.

Myelin sheath, as the multilayer dense structure enclosing axons in humans and other higher organisms, may rupture due to various injury factors after spinal cord injury, thus producing myelin debris. The myelin debris contains a variety of myelin-associated inhibitors (MAIs) and lipid, all inhibiting the repair after spinal cord injury. Through summary and analysis, the present authors found that the inhibition of myelin debris can be mainly divided into two categories: firstly, the direct inhibition mediated by MAIs; secondly, the indirect inhibition mediated by lipid such as cholesterol. It is worth noting that phagocytes are required in the latter indirect inhibition, such as professional phagocytes (macrophages et al.) and non-professional phagocytes (astrocytes et al.). Moreover, complement and the immune system also participate in the phagocytosis of myelin debris, working together with phagocytes to aggravate spinal cord injury. In conclusion, this paper focuses on the direct and indirect effects of myelin debris on spinal cord injury, aiming to provide new inspiration and reflection for the basic research of spinal cord injury and the conception of related treatment.

Galectins are a member of the β-galactoside binding protein family, which play a pivotal role in the immune defense of vertebrates as a pattern recognition receptor and occupy an important position in the innate immune system of invertebrates. The study of galectins in aquatic organisms has only recently emerged. Galectins in aquatic animals exhibit agglutination activity toward bacteria, inhibit bacterial growth, and enhance phagocytosis of immune cells. Additionally, some galectins contribute to the antiviral immune defenses of aquatic animals. This review aims to review recent advancements in the antimicrobial mechanisms, molecular structures, and evolution of galectins from fish, mollusks, and crustaceans. The antimicrobial galectins, as crucial components in the innate immune defense, pave new avenues for developing innovative disease control strategies in aquaculture.

Galectins belong to a family of galactoside-binding proteins and exhibit diverse biological functions. In the present research, a tandem-repeat type galectin (named ToGalectin) was identified from obscure puffer Takifugu obscurus. The 296 amino acids ToGalectin contained two carbohydrate recognition domains (CRDs), one of which possessed two conserved carbohydrate binding motifs. Phylogenetic analysis showed that ToGalectin clustered tightly with other galectin-8 proteins from teleost fish. ToGalectin transcripts were ubiquitously expressed in all tissues examined and its expression was significantly upregulated in the liver, kidney, and intestine after Vibrio harveyi or Staphylococcus aureus infection. To investigate the effect of carbohydrate binding sites on biological activity, ToGalectin and its mutant (MUT-ToGalectin) were expressed and purified. The recombinant ToGalectin and MUT-ToGalectin proteins showed strong agglutinating activity against both V. harveyi and S. aureus. rToGalectin could bind to all tested carbohydrates and bacteria, whereas rMUT-ToGalectin bound to some carbohydrates and bacteria with specific and relatively strong affinity. rToGalectin significantly suppressed the growth of all six bacteria detected and promoted bacterial clearance in vivo, whereas MUT-ToGalectin inhibited the growth of only two bacterial species, which could be attributed to the differences in conserved motifs within the CRDs. Our results suggested that ToGalectin is involved in the immune response against bacterial infection and the clearance of pathogens in T. obscurus.

Eriocheir sinensis (Chinese mitten crab) is one of the main economic species in China, which has evolved an extremely sophisticated innate immune system to fend off disease invasions. However, bacterial and viral infections have caused significant financial losses for the E. sinensis aquaculture in recent years. Making well-informed judgments for the control microbial infections would require a thorough understanding and clarification of the intricate innate immune system of E. sinensis. Innate immunity is essential for the host's defense against invasive pathogens. Pattern recognition receptors (PRRs) initially recognize pathogen-associated molecular patterns (PAMPs) and trigger an innate immune response, causing the generation of inflammatory cytokine and promoting the clearance and control of pathogens. In E. sinensis, Toll/Toll-like receptors, lipopolysaccharide and β-1,3-glucan binding proteins, C-type lectins, galactoside-binding lectins, L-type lectins, scavenger receptors, and down syndrome cell adhesion molecules have been identified to be PRRs that are involved in the recognition of bacteria, fungi, and viruses. In this review, we give a comprehensive overview of the literature regarding PRRs' roles in the immunological defenses of E. sinensis, with the aim of providing clues to the mechanisms of innate immunity.

In recent years, knowledge regarding immune regulation has expanded rapidly, and major advancements have been made in immunotherapy for immune-associated disorders, particularly cancer. The programmed cell death 1 (PD-1) pathway is a cornerstone in immune regulation. It comprises PD-1 and its ligands mediating immune tolerance mechanisms and immune homeostasis. Accumulating evidence demonstrates that the PD-1 axis has a crucial immunosuppressive role in the tumor microenvironment and autoimmune diseases. PD-1 receptors and ligands on immune cells and renal parenchymal cells aid in maintaining immunological homeostasis in the kidneys. Here, we present a comprehensive review of PD-1 immunology in various kidney disorders, including renal cell carcinoma, glomerulonephritis, kidney transplantation, renal aging, and renal immune-related adverse events secondary to PD-1 immunotherapy.

Single-domain von Willebrand factor type C (SVWC) constitute a protein family predominantly identified in arthropods, characterized by a SVWC domain and involved in diverse physiological processes such as host defense, stress resistance, and nutrient metabolism. Nevertheless, the physiological mechanisms underlying these functions remain inadequately comprehended.

A massive expansion of the SVWC gene family in Musca domestica (MdSVWC) was discovered, with a count of 35. MdSVWC1 was selected as the representative of the SVWC family for functional analysis, which led to the identification of the immune function of MdSVWC1 as a novel pattern recognition receptor. MdSVWC1 is highly expressed in both the fat body and intestines and displays acute induction upon bacterial infection. Recombinant MdSVWC1 binds to surfaces of both bacteria and yeast through the recognition of multiple pathogen-associated molecular patterns and exhibits Ca2+-dependent agglutination activity. MdSVWC1 mutant flies exhibited elevated mortality and hindered bacterial elimination following bacterial infection as a result of reduced hemocyte phagocytic capability and weakened expression of antimicrobial peptide (AMP) genes. In contrast, administration of recombinant MdSVWC1 provided protection to flies from bacterial challenges by promoting phagocytosis and AMP genes expression, thereby preventing bacterial colonization. MdSPN16, a serine protease inhibitor, was identified as a target protein of MdSVWC1. It was postulated that the interaction of MdSVWC1 with MdSPN16 would result in the activation of an extracellular proteolytic cascade, which would then initiate the Toll signaling pathway and facilitate the expression of AMP genes.

MdSVWC1 displays activity as a soluble pattern recognition receptor that regulates cellular and humoral immunity by recognizing microbial components and facilitating host defense.

Ovarian cancer remains a formidable challenge in oncology due to its late-stage diagnosis and limited treatment options. Recent research has revealed the intricate interplay between glycan diversity and the immune microenvironment within ovarian tumors, shedding new light on potential therapeutic strategies. This review seeks to investigate the complex role of glycans in ovarian cancer and their impact on the immune response. Glycans, complex sugar molecules decorating cell surfaces and secreted proteins, have emerged as key regulators of immune surveillance in ovarian cancer. Aberrant glycosylation patterns can promote immune evasion by shielding tumor cells from immune recognition, enabling disease progression. Conversely, certain glycan structures can modulate the immune response, leading to either antitumor immunity or immune tolerance. Understanding the intricate relationship between glycan diversity and immune interactions in ovarian cancer holds promise for the development of innovative therapeutic approaches. Immunotherapies that target glycan-mediated immune evasion, such as glycan-based vaccines or checkpoint inhibitors, are under investigation. Additionally, glycan profiling may serve as a diagnostic tool for patient stratification and treatment selection. This review underscores the emerging importance of glycan diversity in ovarian cancer, emphasizing the potential for unraveling immune interplay and advancing tailored therapeutic prospects for this devastating disease.

Legume lectins are a diverse family of carbohydrate-binding proteins that share significant similarities in their primary, secondary, and tertiary structures, yet exhibit remarkable variability in their quaternary structures and carbohydrate-binding specificities. The tertiary structure of legume lectins, characterized by a conserved β-sandwich fold, provides the scaffold for the formation of a carbohydrate-recognition domain (CRD) responsible for ligand binding. The structural basis for the binding is similar between members of the family, with key residues interacting with the sugar through hydrogen bonds, hydrophobic interactions, and van der Waals forces. Variability in substructures and residues within the CRD are responsible for the large array of specificities and enable legume lectins to recognize diverse sugar structures, while maintaining a consistent structural fold. Therefore, legume lectins can be classified into several specificity groups based on their preferred ligands, including mannose/glucose-specific, N-acetyl-d-galactosamine/galactose-specific, N-acetyl-d-glucosamine-specific, l-fucose-specific, and α-2,3 sialic acid-specific lectins. In this context, this review examined the structural aspects and carbohydrate-binding properties of representative legume lectins and their specific ligands in detail. Understanding the structure/binding relationships of lectins continues to provide valuable insights into their biological roles, while also assisting in the potential applications of these proteins in glycobiology, diagnostics, and therapeutics.

Galectin-3 (Gal-3) is a pleiotropic lectin produced by most cell types, which regulates multiple cellular processes in various tissues. In bone, depending on its cellular localization, Gal-3 has a dual and opposite role. If, on the one hand, intracellular Gal-3 promotes bone formation, on the other, its circulating form affects bone remodeling, antagonizing osteoblast differentiation and increasing osteoclast activity. From an analysis of the secretome of cultured differentiating myoblasts, we interestingly found the presence of Gal-3. After that, we confirmed that Gal-3 was expressed and released in the extracellular environment from myoblast cells during their differentiation into myotubes, as well as after mechanical strain. An in vivo analysis revealed that Gal-3 was triggered by trained exercise and was specifically produced by fast muscle fibers. Speculating a role for this peptide in the muscle-to-bone cross talk, a direct co-culture in vitro system, simultaneously combining media that were obtained from differentiated myoblasts and osteoblast cells, confirmed that Gal-3 is a mediator of osteoblast differentiation. Molecular and proteomic analyses revealed that the secreted Gal-3 modulated the biochemical processes occurring in the early phases of bone formation, in particular impairing the activity of the STAT3 and PDK1/Akt signaling pathways and, at the same time, triggering that one of Notch. Circulating Gal-3 also affected the expression of the most common factors involved in osteogenetic processes, including BMP-2, -6, and -7. Intriguingly, Gal-3 was able to interfere with the ability of differentiating osteoblasts to interact with the components of the extracellular bone matrix, a crucial condition required for a proper osteoblast differentiation. All in all, our evidence lays the foundation for further studies to present this lectin as a novel myokine involved in muscle-to-bone crosstalk.

Lectin-based approaches remain a valuable tool for analyzing glycosylation, especially when detecting cancer-related changes. Certain glycans function as platforms for cell communication, signal transduction, and adhesion. Therefore, the functions of glycans are important considerations for clinical aspects, such as cancer, infection, and immunity. Considering that the three-dimensional structure and multivalency of glycans are important factors for their function, their binding characteristics toward lectins provide vital information. Glycans and lectins are inextricably linked, and studies on lectins have also led to research on the roles of glycans. The applications of lectins are not limited to analysis but can also be used as drug delivery tools. Moreover, mammalian lectins are potential therapeutic targets because certain lectins change their expression in cancer, and lectin regulation subsequently regulates several molecules with glycans. Herein, we review lectin-based approaches for analyzing the role of glycans and their clinical applications in diseases, as well as our recent results.

Successful pregnancy relies on a coordinated interplay between endocrine, immune, and metabolic processes to sustain fetal growth and development. The orchestration of these processes involves multiple signaling pathways driving cell proliferation, differentiation, angiogenesis, and immune regulation necessary for a healthy pregnancy. Among the molecules supporting placental development and maternal tolerance, the families of pregnancy-specific glycoproteins and galectins are of great interest in reproductive biology. We previously found that PSG1 can bind to galectin-1 (GAL-1). Herein, we characterized the interaction between PSG1 and other members of the galectin family expressed during pregnancy, including galectin-3, -7, -9, and -13 (GAL-3, GAL-7, GAL-9, and GAL-13). We observed that PSG1 binds to GAL-1, -3, and -9, with the highest apparent affinity seen for GAL-9, and that the interaction of PSG1 with GAL-9 is carbohydrate-dependent. We further investigated the ability of PSG1 to regulate GAL-9 responses in human monocytes, a murine macrophage cell line, and T-cells, and determined whether PSG1 binds to both carbohydrate recognition domains of GAL-9. Additionally, we compared the apparent affinity of GAL-9 binding to PSG1 with other known GAL-9 ligands in these cells, Tim-3 and CD44. Lastly, we explored functional conservation between murine and human PSGs by determining that Psg23, a highly expressed member of the murine Psg family, can bind some murine galectins despite differences in amino acid composition and domain structure.

Mesenchymal stem cells (MSCs) are commonly employed as a powerful tool for the treatment of immune-mediated problems owing to their capacity to regulate the immune system and differentiate into different tissues. Researchers use mesenchymal stem cell products given the limitations associated with the application of MSCs. Exosomes are nanometer vesicles derived from MSCs that are used in cell-free therapy. Inflammatory environmental conditions, such as stimulation of Toll-like receptor 3 (TLR-3), has the ability to adjust the immune-regulating properties and anti-inflammatory function of mesenchymal stem cells and their exosomes. Galectins and hepatocyte growth factor (HGF) are known as immunomodulatory factors in mesenchymal stem cells. This study was designed to examine the expression of galectin-1, galectin-3, galectin-9, and HGF genes in exosomes isolated from human Wharton's jelly mesenchymal stem cells (hWJ-MSCs) after stimulation with Poly (I:C) (Polyinosinic:polycytidylic acid sodium salt).

To begin, the explant technique was used to extract mesenchymal stem cells from human umbilical cord Wharton's jelly. Then, the stem cells were stimulated using Poly (I:C) at three time intervals of 12, 24 and 48 h. Exosomes secreted from the supernatant of cells were extracted and exosome confirmation tests, including Scanning electron microscopy (SEM), Dynamic light scattering (DLS) and Flow cytometry were performed. Finally, the expression of galectin-1, galectin-3, galectin-9, and HGF genes in exosomes was evaluated by Real-Time PCR at three time intervals of 12, 24 and 48 h after stimulation.

The findings of our study indicated that following stimulation with Poly (I:C), the expression of galectin-9 and HGF (P < 0.05) genes was markedly higher than in the control group after 12 h. After 24 h, the expression of galectin-9 (P < 0.01), galectin-3 and HGF (P < 0.05) increased; the expression of galectin-1, galectin-3, (P < 0.05), galectin-9 and HGF genes (p < 0.01) significantly increased compared to the control group after 48 h.

TLR3 stimulation can increase the expression of galectins and HGF genes in exosomes derived from hWJ-MSCs and may be improve the immunosuppressive abilities of exosomes.

Galectin-3 belongs to a family of soluble glycan-binding proteins, which are increasingly recognized as modulators of pregnancy-associated processes, including proper placental development. Gestational hypertension and preeclampsia are significant complications of pregnancy, affecting millions of women annually. Despite their prevalence, the underlying pathophysiological mechanisms remain poorly understood. Several theories have been proposed, including inflammation, placental insufficiency, disturbed placental invasion, and angiogenesis. The Scopus and PubMed/MEDLINE databases were utilized until the end of May 2024. In total, 11 articles with 1011 patients, with 558 in the control group and 453 in the preeclampsia group, were included. Seven articles investigated the expression of galectin-3 (Gal-3) in placental tissue samples, eight studies calculated the serum levels of Gal-3 in maternal blood samples, while one study referred to the possible correlation of galectin-3 levels in umbilical cord blood. The results were inconsistent in both the placental tissue and maternal serum; Gal-3 placental expression was found to be statistically increased in five studies compared to that in women without gestational hypertensive disorders, while two studies either mentioned decreased expression or no difference. Similarly, the Gal-3 maternal serum levels, compared to those in women without gestational hypertensive disorders, were found to be statistically increased in five studies, while three studies did not find any statistical difference. Gal-3 can play a crucial role in the pathogenesis of preeclampsia, and its expression is influenced by gestational age and placental insufficiency. A further investigation ought to be conducted to enlighten the correlation of Gal-3 with gestational hypertension and preeclampsia development.

Plant-based diets are associated with a lower risk of chronic diseases. Large-scale proteomics can identify objective biomarkers of plant-based diets, and improve our understanding of the pathways that link plant-based diets to health outcomes. This study investigated the plasma proteome of four different plant-based diets [overall plant-based diet (PDI), provegetarian diet, healthful plant-based diet (hPDI), and unhealthful plant-based diet (uPDI)] in the Atherosclerosis Risk in Communities (ARIC) Study and replicated the findings in the Framingham Heart Study (FHS) Offspring cohort.

ARIC Study participants at visit 3 (1993-1995) with completed food frequency questionnaire (FFQ) data and proteomics data were divided into internal discovery (n = 7690) and replication (n = 2543) data sets. Multivariable linear regression was used to examine associations between plant-based diet indices (PDIs) and 4955 individual proteins in the discovery sample. Then, proteins that were internally replicated in the ARIC Study were tested for external replication in FHS (n = 1358). Pathway overrepresentation analysis was conducted for diet-related proteins. C-statistics were used to predict if the proteins improved prediction of plant-based diet indices beyond participant characteristics.

In ARIC discovery, a total of 837 diet-protein associations (PDI = 233; provegetarian = 182; hPDI = 406; uPDI = 16) were observed at false discovery rate (FDR) < 0.05. Of these, 453 diet-protein associations (PDI = 132; provegetarian = 104; hPDI = 208; uPDI = 9) were internally replicated. In FHS, 167/453 diet-protein associations were available for external replication, of which 8 proteins (PDI = 1; provegetarian = 0; hPDI = 8; uPDI = 0) replicated. Complement and coagulation cascades, cell adhesion molecules, and retinol metabolism were over-represented. C-C motif chemokine 25 for PDI and 8 proteins for hPDI modestly but significantly improved the prediction of these indices individually and collectively (P value for difference in C-statistics<0.05 for all tests).

Using large-scale proteomics, we identified potential candidate biomarkers of plant-based diets, and pathways that may partially explain the associations between plant-based diets and chronic conditions.

This study aimed to investigate the role of galectin-3 (Gal-3; coded by LGALS3 gene), as a biomarker for MCI in T2DM patients and to develop and validate a predictive nomogram integrating galectin-3 with clinical risk factors for MCI prediction. Additionally, microRNA regulation of LGALS3 was explored.

The study employed a cross-sectional design. A total of 329 hospitalized T2DM patients were recruited and randomly allocated into a training cohort (n = 231) and a validation cohort (n = 98) using 7:3 ratio. Demographic data and neuropsychological assessments were recorded for all participants. Plasma levels of galectin-3 were measured using ELISA assay. We employed Spearman's correlation and multivariable linear regression to analyze the relationship between galectin-3 levels and cognitive performance. Furthermore, univariate and multivariate logistic regression analyses were conducted to identify independent risk factors for MCI in T2DM patients. Based on these analyses, a predictive nomogram incorporating galectin-3 and clinical predictors was developed. The model's performance was evaluated in terms of discrimination, calibration, and clinical utility. Regulatory miRNAs were identified using bioinformatics and their interactions with LGALS3 were confirmed through qRT-PCR and luciferase reporter assays.

Galectin-3 was identified as an independent risk factor for MCI, with significant correlations to cognitive decline in T2DM patients. The developed nomogram, incorporating Gal-3, age, and education levels, demonstrated excellent predictive performance with an AUC of 0.813 in the training cohort and 0.775 in the validation cohort. The model outperformed the baseline galectin-3 model and showed a higher net benefit in clinical decision-making. Hsa-miR-128-3p was significantly downregulated in MCI patients, correlating with increased Gal-3 levels, while Luciferase assays confirmed miR-128-3p's specific binding and influence on LGALS3.

Our findings emphasize the utility of Gal-3 as a viable biomarker for early detection of MCI in T2DM patients. The validated nomogram offers a practical tool for clinical decision-making, facilitating early interventions to potentially delay the progression of cognitive impairment. Additionally, further research on miRNA128's regulation of Gal-3 levels is essential to substantiate our results.

Intravascular hemolysis is a central feature of congenital and acquired hemolytic anemias, complement disorders, infectious diseases, and toxemias. Massive and/or chronic hemolysis is followed by the induction of inflammation, very often with severe damage of organs, which enhances the morbidity and mortality of hemolytic diseases. Galectin-3 (Gal-3) is a β-galactoside-binding lectin that modulates the functions of many immune cells, thus affecting inflammatory processes. Gal-3 is also one of the main regulators of fibrosis. The role of Gal-3 in the development of different kidney and liver diseases and the potential of therapeutic Gal-3 inhibition have been demonstrated. Therefore, the objective of this review is to discuss the possible effects of Gal-3 on the process of kidney and liver damage induced by intravascular hemolysis, as well as to shed light on the potential therapeutic targeting of Gal-3 in intravascular hemolysis.