Bridging the Gap between Galectin-3 Expression and Hypertensive Pregnancy Disorders: A Narrative Review.

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.

Polymorphism Pro64His within galectin-3 has functional consequences at proteome level in thyroid cells.

Introduction: The single nucleotide polymorphism (SNP) rs4644 at codon 64 of galectin-3 (gal-3, gene name: LGALS3), specifying the variant proline (P64) to histidine (H64), is known to affect the protein's functions and has been associated with the risk of several types of cancer, including differentiated thyroid carcinoma (DTC). Materials and methods: To deepen our understanding of the biological effects of this SNP, we analyzed the proteome of two isogenic cell lines (NC-P64 vs. NA-H64) derived from the immortalized non-malignant thyrocyte cell line Nthy-Ori, generated through the CRISPR-Cas9 technique to differ by rs4644 genotype. We compared the proteome of these cells to detect differentially expressed proteins and studied their proteome in relation to their transcriptome. Results: Firstly, we found, consistently with previous studies, that gal-3-H64 could be detected as a monomer, homodimer, and heterodimer composed of one cleaved and one uncleaved monomer, whereas gal-3-P64 could be found only as a monomer or uncleaved homodimer. Moreover, results indicate that rs4644 influences the expression of several proteins, predominantly upregulated in NA-H64 cells. Overall, the differential protein expression could be attributed to the altered mRNA expression, suggesting that rs4644 shapes the function of gal-3 as a transcriptional co-regulator. However, this SNP also appeared to affect post-transcriptional regulatory mechanisms for proteins whose expression was oppositely regulated compared to mRNA expression. It is conceivable that the rs4644-dependent activities of gal-3 could be ascribed to the different modalities of self-dimerization. Conclusion: Our study provided further evidence that rs4644 could affect the gal-3 functions through several routes, which could be at the base of differential susceptibility to diseases, as reported in case-control association studies.

Calpain Small Subunit Mediated Secretion of Galectin-3 Regulates Traction Stress.

The complex regulation of traction forces (TF) produced during cellular migration remains poorly understood. We have previously found that calpain 4 (Capn4), the small non-catalytic subunit of the calpain 1 and 2 proteases, regulates the production of TF independent of the proteolytic activity of the larger subunits. Capn4 was later found to facilitate tyrosine phosphorylation and secretion of the lectin-binding protein galectin-3 (Gal3). In this study, recombinant Gal3 (rGal3) was added to the media-enhanced TF generated by capn4-/- mouse embryonic fibroblasts (MEFs). Extracellular Gal3 also rescued defects in the distribution, morphology, and adhesive strength of focal adhesions present in capn4-/- MEF cells. Surprisingly, extracellular Gal3 does not influence mechanosensing. c-Abl kinase was found to affect Gal3 secretion and the production of TF through phosphorylation of Y107 on Gal3. Our study also suggests that Gal3-mediated regulation of TF occurs through signaling pathways triggered by ß1 integrin but not by focal adhesion kinase (FAK) Y397 autophosphorylation. Our findings provide insights into the signaling mechanism by which Capn4 and secreted Gal3 regulate cell migration through the modulation of TF distinctly independent from a mechanosensing mechanism.

Identification of benzothiazole derived monosaccharides as potent, selective, and orally bioavailable inhibitors of human and mouse galectin-3; a rare example of using a S···O binding interaction for drug design.

As a result of our continued efforts to pursue Gal-3 inhibitors that could be used to fully evaluate the potential of Gal-3 as a therapeutic target, two novel series of benzothiazole derived monosaccharides as potent (against both human and mouse Gal-3) and orally bioavailable Gal-3 inhibitors, represented by 4 and 5, respectively, were identified. These discoveries were made based on proposals that the benzothiazole sulfur atom could interact with the carbonyl oxygen of G182/G196 in h/mGal-3, and that the anomeric triazole moiety could be modified into an N-methyl carboxamide functionality. The interaction between the benzothiazole sulfur and the carbonyl oxygen of G196 in mGal-3 was confirmed by an X-ray co-crystal structure of early lead 9, providing a rare example of using a S···O binding interaction for drug design. It was found that for both the series, methylation of 3-OH in the monosaccharides caused no loss in h & mGal-3 potencies but significantly improved permeability of the molecules.

Resistance to anti-PD-1/anti-PD-L1: galectin-3 inhibition with GB1211 reverses galectin-3-induced blockade of pembrolizumab and atezolizumab binding to PD-1/PD-L1.

Background: Galectin-3 (Gal-3) is a ß-galactoside-binding lectin that is highly expressed within the tumor microenvironment of aggressive cancers and has been suggested to predict a poor response to immune checkpoint therapy with the anti-PD-1 monoclonal antibody pembrolizumab. We aimed to assess if the effect of Gal-3 was a result of direct interaction with the immune checkpoint receptor. Methods: The ability of Gal-3 to interact with the PD-1/PD-L1 complex in the absence and presence of blocking antibodies was assessed in in vitro biochemical and cellular assays as well as in an in vivo syngeneic mouse cancer model. Results: Gal-3 reduced the binding of the checkpoint inhibitors pembrolizumab (anti-PD-1) and atezolizumab (anti-PD-L1), by potentiating the interaction between the PD-1/PD-L1 complex. In the presence of a highly selective Gal-3 small molecule inhibitor (GB1211) the binding of the anti-PD-1/anti-PD-L1 therapeutics was restored to control levels. This was observed in both a surface plasmon resonance assay measuring protein-protein interactions and via flow cytometry. Combination therapy with GB1211 and an anti-PD-L1 blocking antibody reduced tumor growth in an in vivo syngeneic model and increased the percentage of tumor infiltrating T lymphocytes. Conclusion: Our study suggests that Gal-3 can potentiate the PD-1/PD-L1 immune axis and potentially contribute to the immunosuppressive signalling mechanisms within the tumor microenvironment. In addition, Gal-3 prevents atezolizumab and pembrolizumab target engagement with their respective immune checkpoint receptors. Reversal of this effect with the clinical candidate GB1211 offers a potential enhancing combination therapeutic with anti-PD-1 and -PD-L1 blocking antibodies.

Galectin-3 shapes toxic alpha-synuclein strains in Parkinson's disease.

Parkinson's Disease (PD) is a neurodegenerative and progressive disorder characterised by intracytoplasmic inclusions called Lewy bodies (LB) and degeneration of dopaminergic neurons in the substantia nigra (SN). Aggregated α-synuclein (αSYN) is known to be the main component of the LB. It has also been reported to interact with several proteins and organelles. Galectin-3 (GAL3) is known to have a detrimental function in neurodegenerative diseases. It is a galactose-binding protein without known catalytic activity and is expressed mainly by activated microglial cells in the central nervous system (CNS). GAL3 has been previously found in the outer layer of the LB in post-mortem brains. However, the role of GAL3 in PD is yet to be elucidated. In post-mortem samples, we identified an association between GAL3 and LB in all the PD subjects studied. GAL3 was linked to less αSYN in the LB outer layer and other αSYN deposits, including pale bodies. GAL3 was also associated with disrupted lysosomes. In vitro studies demonstrate that exogenous recombinant Gal3 is internalised by neuronal cell lines and primary neurons where it interacts with endogenous αSyn fibrils. In addition, aggregation experiments show that Gal3 affects spatial propagation and the stability of pre-formed αSyn fibrils resulting in short, amorphous toxic strains. To further investigate these observations in vivo, we take advantage of WT and Gal3KO mice subjected to intranigral injection of adenovirus overexpressing human αSyn as a PD model. In line with our in vitro studies, under these conditions, genetic deletion of GAL3 leads to increased intracellular αSyn accumulation within dopaminergic neurons and remarkably preserved dopaminergic integrity and motor function. Overall, our data suggest a prominent role for GAL3 in the aggregation process of αSYN and LB formation, leading to the production of short species to the detriment of larger strains which triggers neuronal degeneration in a mouse model of PD.

Galectin-3 (MAC-2) controls phagocytosis and macropinocytosis through intracellular and extracellular mechanisms.

Galectin-3 (Gal-3; formally named MAC-2) is a ß-galactoside-binding lectin. Various cell types produce Gal-3 under either normal conditions and/or pathological conditions. Gal-3 can be present in cells' nuclei and cytoplasm, secreted from producing cells, and associated with cells' plasma membranes. This review focuses on how Gal-3 controls phagocytosis and macropinocytosis. Intracellular and extracellular Gal-3 promotes the phagocytosis of phagocytic targets/cargo (e.g., tissue debris and apoptotic cells) in "professional phagocytes" (e.g., microglia and macrophages) and "non-professional phagocytes" (e.g., Schwann cells and astrocytes). Intracellularly, Gal-3 promotes phagocytosis by controlling the "eat me" signaling pathways that phagocytic receptors generate, directing the cytoskeleton to produce the mechanical forces that drive the structural changes on which phagocytosis depends, protrusion and then retraction of filopodia and lamellipodia as they, respectively, engulf and then internalize phagocytic targets. Extracellularly, Gal-3 promotes phagocytosis by functioning as an opsonin, linking phagocytic targets to phagocytic receptors, activating them to generate the "eat me" signaling pathways. Macropinocytosis is a non-selective endocytic mechanism that various cells use to internalize the bulk of extracellular fluid and included materials/cargo (e.g., dissolved nutrients, proteins, and pathogens). Extracellular and intracellular Gal-3 control macropinocytosis in some types of cancer. Phagocytosed and macropinocytosed targets/cargo that reach lysosomes for degradation may rupture lysosomal membranes. Damaged lysosomal membranes undergo either repair or removal by selective autophagy (i.e., lysophagy) that intracellular Gal-3 controls.

Renal Function Impact in the Prognostic Value of Galectin-3 in Acute Heart Failure.

Introduction: Galectin-3 (Gal-3) is an inflammatory marker associated with the development and progression of heart failure (HF). A close relationship between Gal-3 levels and renal function has been observed, but data on their interaction in patients with acute HF (AHF) are scarce. We aim to assess the prognostic relationship between renal function and Gal-3 during an AHF episode. Materials and Methods: This is an observational, prospective, multicenter registry of patients hospitalized for AHF. Patients were divided into two groups according to estimated glomerular filtration rate (eGFR): preserved renal function (eGFR ≥ 60 mL/min/1.73 m2) and renal dysfunction (eGFR <60 mL/min/1.73 m2). Cox regression analysis was performed to evaluate the association between Gal-3 and 12-month mortality. Results: We included 1,201 patients in whom Gal-3 values were assessed at admission. The median value of Gal-3 in our population was 23.2 ng/mL (17.3-32.1). Gal-3 showed a negative correlation with eGFR (rho = -0.51; p < 0.001). Gal-3 concentrations were associated with higher mortality risk in the multivariate analysis after adjusting for eGFR and other prognostic variables [HR = 1.010 (95%-CI: 1.001-1.018); p = 0.038]. However, the prognostic value of Gal-3 was restricted to patients with renal dysfunction [HR = 1.010 (95%-CI: 1.001-1.019), p = 0.033] with optimal cutoff point of 31.5 ng/mL, with no prognostic value in the group with preserved renal function [HR = 0.990 (95%-CI: 0.964-1.017); p = 0.472]. Conclusions: Gal-3 is a marker of high mortality in patients with acute HF and renal dysfunction. Renal function influences the prognostic value of Gal-3 levels, which should be adjusted by eGFR for a correct interpretation.

Galectin-3 promotes calcification of human aortic valve interstitial cells via the NF-kappa B signaling pathway.

Background: Calcific aortic valve disease (CAVD) is an active pathobiological process that takes place at the cellular and molecular levels. It involves fibrosis and calcification of aortic valve leaflets, which eventually contributes to heart failure. Galectin-3 (Gal-3), a ß-galactoside-binding lectin, is involved in myocardial fibrosis and remodeling. Our study aimed to explore how Gal-3 promoted the osteogenic differentiation of human aortic valve interstitial cells (hVICs) along with elucidating the underlying molecular mechanisms. Methods: To determine the Gal-3 expression in this study, we included the blood samples and aortic valves (AVs) from patients with CAVD (n=20) and normal controls (n=20). The hVICs were stimulated by Osteogenic medium (OM) and were treated with or without recombinant human Gal-3. Calcified transformation of hVICs was assessed by Alizarin Red S staining and osteogenic gene/protein expression. RNA-sequencing was performed for all different treatments to investigate differentially expressed genes (DEGs) along with exploring the enriched pathways for potential molecular targets of Gal-3. The targets were further detected using Western blotting and immunofluorescence staining. Results: Gal-3 levels were found to be significantly increased in CAVD patients. Treatment of valve interstitial cells (VICs) with Gal-3 led to a marked increase in Runx2 and ALP-mRNA/protein expression levels as well as calcification. Gene expression profiles of hVICs cultured with or without Gal-3 revealed 79 upregulated genes and 82 down-regulated genes, which were highly enriched in TNF and NF-κB signaling pathways. Furthermore, Gal-3 could activate the phosphorylation of IκBα and interfere with the translocation of p65 into the cell nucleus of hVICs. However, inhibition of this pathway can suppress the osteogenic differentiation by Gal-3. Conclusions: Gal-3 acts as a positive regulator of osteogenic differentiation by activating the NF-κB signaling pathway in hVICs. Our findings provide novel mechanistic insights into the critical role of Gal-3 in the CAVD progression.

Dang Gui Bu Xue Tang, a conventional Chinese herb decoction, ameliorates radiation-induced heart disease via Nrf2/HMGB1 pathway.

Introduction: Radiation-induced heart disease (RIHD), characterized by cardiac dysfunction and myocardial fibrosis, is one of the most common complications after cardiothoracic radiotherapy. Dang Gui Bu Xue Tang (DBT) is a conventional Chinese herb decoction composed of Radix Astragali membranaceus (RAM) and Radix Angelicae sinensis (RAS) at a ratio of 5:1, famous for its "blood-nourishing" effect. In this study, we aimed to investigate the cardioprotective effect of DBT on RIHD. Methods: C57BL mice at 8 weeks of age were divided into five groups, namely Control, Radiation, RDBT51 (Radiation with DBT, RAM:RAS = 5:1), RDBT11 (Radiation with DBT, RAM:RAS = 1:1), and RDBT15 (Radiation with DBT, RAM:RAS = 1:5). Results: We mainly found that radiation in the cardiothoracic region led to significant left ventricular systolic dysfunction, myocardial fibrotic lesions and cardiac injury accompanied by abnormally increased myocardial HMGB1 protein levels. Administration of conventional DBT significantly ameliorated left ventricular systolic dysfunction, alleviated myocardial fibrosis, and counteracted cardiac injury, all of which supported the protective effect of DBT on RIHD, involving upregulation of myocardial Nrf2 protein levels and downregulation of HMGB1 protein levels as underlying mechanisms. Conclusions: DBT exerts a significant protective effect on RIHD, and the Nrf2/ HMGB1 pathway probably plays an important role in this protective effect.

The Role of Galectin-3 in 1α,25(OH)2D3-Regulated Osteoclast Formation from White Leghorn Chickens In Vitro.

Bones play an important role in maintaining the level of calcium in blood. They provide support for soft tissues and hematopoiesis and undergo continuous renewal throughout life. In addition, vitamin D is involved in regulating bone and calcium homeostasis. Galectin-3 (Gal-3) is a ß-galactoside-binding protein that can regulate bone cell differentiation and function. Here, we aimed to study the regulatory effects of Gal-3 on vitamin-D-regulated osteoclastogenesis and bone resorption in chicken. Gal-3 expression in bone marrow stromal cells (BMSCs) from 18-day-old chicken embryos was inhibited or overexpressed. BMSCs were then co-cultured with bone marrow monocytes/macrophages (BMMs) with or without addition of 1α,25(OH)2D3. The results showed that 1α,25(OH)2D3 upregulated the expression of Gal-3 mRNA and receptor activator of nuclear-factor κB ligand (RANKL) expression in BMSCs and promoted osteoclastogenesis, as shown by the upregulated expression of osteoclast (OC) markers (CtsK, CAII, MMP-9, and TRAP) and increased bone resorption, a method for measuring the bone resorption area in vitro. Knockdown of Gal-3 by small-interfering RNA (siRNA) in BMSCs downregulated the expression of RANKL mRNA and attenuated the effects of 1α,25(OH)2D3 on osteoclastogenesis and bone resorption. Conversely, overexpression of Gal-3 in BMSCs enhanced the effects of osteoclastogenesis and bone resorption by increasing the expression of RANKL mRNA. These results demonstrated that Gal-3 mediates the differentiation and bone resorption of osteoclasts regulated by 1α,25(OH)2D3.

Modified citrus pectin prevents isoproterenol-induced cardiac hypertrophy associated with p38 signalling and TLR4/JAK/STAT3 pathway.

Modified citrus pectin (MCP) is a specific inhibitor of galectin-3 (Gal-3) that is regarded as a new biomarker of cardiac hypertrophy, but its effect is unclear. The aim of this study is to investigate the role and mechanism of MCP in isoproterenol (ISO)-induced cardiac hypertrophy. Rats were injected with ISO to induce cardiac hypertrophy and treated with MCP. Cardiac function was detected by ECG and echocardiography. Pathomorphological changes were evaluated by the haematoxylin eosin (H&E) and wheat germ agglutinin (WGA) staining. The hypertrophy-related genes for atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and ß-myosin heavy chain (ß-MHC), and the associated signal molecules were analysed by qRT-PCR and western blotting. The results show that MCP prevented cardiac hypertrophy and ameliorated cardiac dysfunction and structural disorder. MCP also decreased the levels of ANP, BNP, and ß-MHC and inhibited the expression of Gal-3 and Toll-like receptor 4 (TLR4). Additionally, MCP blocked the phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3), but it promoted the phosphorylation of p38. Thus, MCP prevented ISO-induced cardiac hypertrophy by activating p38 signalling and inhibiting the Gal-3/TLR4/JAK2/STAT3 pathway.

Influence of Galectin-3 on the Innate Immune Response during Experimental Cryptococcosis.

Cryptococcus neoformans, the causative agent of cryptococcosis, is the primary fungal pathogen that affects the immunocompromised individuals. Galectin-3 (Gal-3) is an animal lectin involved in both innate and adaptive immune responses. The present study aimed to evaluate the influence of Gal-3 on the C. neoformans infection. We performed histopathological and gene profile analysis of the innate antifungal immunity markers in the lungs, spleen, and brain of the wild-type (WT) and Gal-3 knockout (KO) mice during cryptococcosis. These findings suggest that Gal-3 absence does not cause significant histopathological alterations in the analyzed tissues. The expression profile of the genes related to innate antifungal immunity showed that the presence of cryptococcosis in the WT and Gal-3 KO animals, compared to their respective controls, promoted the upregulation of the pattern recognition receptor (PRR) responsive to mannose/chitin (mrc1) and a gene involved in inflammation (ccr5), as well as the downregulation of the genes related to signal transduction (card9, fos, ikbkb, jun) and PRRs (cd209a, colec12, nptx1). The absence of Gal-3, in fungal infection, a positively modulated gene involved in phagocytosis (sftpd) and negatively genes involved in signal transduction (syk and myd88), proinflammatory cytokines il-1ß and il-12b and cd209a receptor. Therefore, our results suggest that Gal-3 may play an essential role in the development of antifungal immune responses against cryptococcosis.

Post-stroke Delivery of Valproic Acid Promotes Functional Recovery and Differentially Modifies Responses of Peri-Infarct Microglia.

The specific role of peri-infarct microglia and the timing of its morphological changes following ischemic stroke are not well understood. Valproic acid (VPA) can protect against ischemic damage and promote recovery. In this study, we first determined whether a single dose of VPA after stroke could decrease infarction area or improve functional recovery. Next, we investigated the number and morphological characteristic of peri-infarct microglia at different time points and elucidated the mechanism of microglial response by VPA treatment. Male Sprague-Dawley rats were subjected to distal middle cerebral artery occlusion (dMCAo) for 90 min, followed by reperfusion. Some received a single injection of VPA (200 mg/kg) 90 min after the induction of ischemia, while vehicle-treated animals underwent the same procedure with physiological saline. Infarction volume was calculated at 48 h after reperfusion, and neurological symptoms were evaluated. VPA didn't significantly reduce infarct volume but did ameliorate neurological deficit at least partially compared with vehicle. Meanwhile, VPA reduced dMCAo-induced elevation of IL-6 at 24 h post-stroke and significantly decreased the number of CD11b-positive microglia within peri-infarct cortex at 7 days. Morphological analysis revealed that VPA therapy leads to higher fractal dimensions, smaller soma size and lower circularity index of CD11b-positive cells within peri-infarct cortex at both 2 and 7 days, suggesting that VPA has core effects on microglial morphology. The modulation of microglia morphology caused by VPA might involve HDAC inhibition-mediated suppression of galectin-3 production. Furthermore, qPCR analysis of CD11b-positive cells at 3 days post-stroke suggested that VPA could partially enhance M2 subset polarization of microglia in peri-infarct cortex. Analysis of VPA-induced changes to gene expressions at 3 days post-stroke implies that these alternations of the biomarkers and microglial responses are implicated in the upregulation of wound healing, collagen trimmer, and extracellular matrix genes within peri-infarct cortex. Our results are the first to show that a low dose of VPA promotes short-term functional recovery but does not alter infarct volume. The decreases in the expression of both IL-6 and galectin-3 might influence the morphological characteristics and transcriptional profiles of microglia and extracellular matrix remodeling, which could contribute to the improved recovery.

Effects of laparoscopic and traditional open surgery on the levels of IL-6, TNF-α, and Gal-3 in patients with thyroid cancer.

BACKGROUND: Traditional open surgery and laparoscopic surgery are common treatments for thyroid cancer patients, this paper aims to explore their effects on the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and galectin-3 (Gal-3) in patients with thyroid cancer. METHODS: The clinical data of patients with thyroid cancer who received surgery in our hospital from September 2017 to February 2020 were collected. In total, 106 cases that met the inclusion and exclusion criteria were included. The patients were then allocated into two groups according to the surgery received, including a study group (56 cases treated with endoscopy) and a basic group (50 cases treated with traditional open surgery). Rehabilitation indicators and inflammatory cytokines were compared between the two groups. RESULTS: There was no significant difference in the number of intraoperative lymph node dissections (P>0.05), postoperative complication rate (16.08% vs. 20.00%, P>0.05), and 6-month rate of recurrence or metastasis (P>0.05) between the two groups. Compared to the basic group, the operation time of the study group was longer, while the amount of intraoperative blood loss, 24 h drainage of the catheter and the length of hospital stay were significantly lower in the study group (P<0.05). The pain scores of the study group at 24 and 48 h after surgery were significantly lower than those of the basic group (P<0.05). The levels of IL-6, TNF-α, Gal-3, and other inflammatory factors in the two groups increased on the first day postoperatively, however the levels of these factors in the study group were lower than those in the basic group (P<0.05). Finally, the postoperative cosmetic satisfaction rate of the study group (94.64%) was higher than that of the basic group (86.00%), and the difference was statistically significant (P<0.05). CONCLUSIONS: The use of laparoscopic treatment can reduce the amount of intraoperative blood loss in patients with thyroid cancer, effectively reduce the degree of postoperative pain, and inhibit postoperative inflammation in the patient to a certain extent. Moreover, laparoscopic treatment can increase postoperative cosmetic satisfaction, reduce the occurrence of postoperative complications and recurrence rate, and improve the patient's prognosis.

The utility of growth differentiation factor-15, galectin-3, and sST2 as biomarkers for the diagnosis of heart failure with preserved ejection fraction and compared to heart failure with reduced ejection fraction: a systematic review.

The objective was to evaluate the diagnosis of heart failure with preserved ejection fraction (HFpEF) using the biomarkers, growth differentiation factor-15 (GDF-15), galectin-3 (Gal-3), and soluble ST2 (sST2), and to determine whether they can differentiate HFpEF from heart failure with reduced ejection fraction (HFrEF). Medline and Embase databases were searched with the terms diastolic heart failure or HFpEF, biomarkers, and diagnosis, limited to years 2000 to 2019. There were significantly and consistently higher levels of GDF-15, Gal-3, and sST2 in HFpEF compared to no heart failure. Importantly, the magnitude of the increase in GDF-15 or Gal-3 and possibly sST2,correlated with a greater degree of diastolic dysfunction. There were no significant differences between GDF-15, Gal-3, and sST2 in patients with HFpEF vs HFrEF. In the studies assessing these three biomarkers, BNP was significantly greater in heart failure than controls. Furthermore, BNP was significantly higher in HFrEF compared to HFpEF. The diagnostic utility of GDF-15, Gal-3, and sST2 compared to BNP was evaluated by comparing ROC curves. The data supports the contention that to distinguish HFpEF from HFrEF, an index is needed that incorporates GDF-15, Gal-3, or sST2 as well as BNP. The three biomarkers GDF-15, Gal-3, or sST2 can identify patients with HFpEF compared to individuals without heart failure but cannot differentiate HFpEF from HFrEF. BNP is higher in and is better at differentiating HFrEF from HFpEF. Indices that incorporate GDF-15, Gal-3, or sST2 as well as BNP show promise in differentiating HFpEF from HFrEF.

Gentianella acuta prevents acute myocardial infarction induced by isoproterenol in rats via inhibition of galectin-3/TLR4/MyD88/NF-кB inflammatory signalling.

Gentianella acuta (G. acuta), as a folk medicine, was used to treat heart disease by the Ewenki people in Inner Mongolia. However, the effect of G. acuta on acute myocardial infarction (AMI) is not clear. To explore the mechanisms of G. acuta on isoproterenol (ISO)-induced AMI, rats were administered G. acuta for 28 days, then injected intraperitoneally with ISO (85 mg/kg) on days 29 and 30. An electrocardiogram helped to evaluate the myocardial injury. Serum lactate dehydrogenase (LDH), creatinine kinase (CK) and aspartate aminotransferase (AST) levels were evaluated, and haematoxylin eosin, Masson's trichrome staining and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining were used to detect myocardial histological changes. Radioimmunoassay was used to measure serum tumour necrosis factor alpha (TNFα) and interleukin (IL)-6. An enzyme-linked immunosorbent assay kit was used to analyse serum galectin-3 (Gal-3) levels. Immunohistochemistry, Western blotting and reverse transcription polymerase chain reaction were used to examine relevant molecular events. The results revealed that pre-treatment with G. acuta decreased the elevation in the ST segment; reduced serum LDH, CK and AST levels; alleviated cardiac structure disorder; and reduced inflammatory infiltration, abnormal collagen deposition and cardiomyocyte apoptosis that were induced by ISO. Furthermore, pre-treatment with G. acuta inhibited serum Gal-3 levels and Gal-3 expression in heart tissue, and also impeded TLR4/MyD88/NF-кB signalling activation, which ultimately prevented the expression of inflammatory cytokines. The study indicated that pre-treatment with G. acuta protects against ISO-induced AMI, and the protective role may be related to inhibiting Gal-3/TLR4/MyD88/NF-кB inflammatory signalling.

Soluble ST2, Galectin-3 and clinical prognosis of patients with hypertrophic cardiomyopathy undergoing ventricular septal myectomy: a correlation analysis.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common chromosomal abnormal heart disease. The pathophysiological mechanism of HCM is complex. Several studies have suggested that the level of Soluble ST2 (sST2) may be a biomarker of chronic systolic heart failure, however, the role of sST2 in HCM remains unclear. So we performed this study to analyze the role of Soluble ST2 (sST2), Galectin-3 (Gal-3) and its correlations with clinical prognosis of patients with hypertrophic cardiomyopathy (HCM) undergoing ventricular septal myectomy. METHODS: HCM patients who underwent modified Morrow surgery in our hospital during June 2016-June 2018 were included. We divided the patients into different groups stratified by sST2 and Gal-3 level. Besides, we included volunteers without heart disease for medical examination as normal controls. Biochemical analyses were conducted to identify the biomarkers difference. The predictive value of sST2 and Gal-3 on all-cause mortality was evaluated with Cox regression analysis. RESULTS: A total of 125 HCM patients were included in this present study. The sST2 and Gal-3 levels in HCM patients were significantly higher than that in control group (all P<0.001); there were significant differences in the incidence of all-cause mortality for HCM patients stratified by the sST2 and Gal-3 level; Cox univariate regression survival analysis showed that the hypertension (HR =1.19, 95% CI: 1.01-1.38), maximum wall thickness (HR =1.48, 95% CI: 1.04-1.98), Log sST2 (HR =1.02, 95% CI: 1.01-1.05), Log Gal-3 (HR =1.17, 95% CI: 1.09-1.32) were the predictors for all-cause mortality in patients with HCM, and Cox multivariate risk regression showed that maximum wall thickness was the independent predictors of all-cause mortality in patients with HCM (HR =1.63, 95% CI: 1.35-1.97). CONCLUSIONS: Even through sST2 and Gal-3 were not associated with clinical prognosis of patients with HCM undergoing ventricular septal myectomy, it may be involved in the progress of HCM, more studies are warranted to identify the potential mechanism and reverence value.

Effect of Gualou Xiebai Banxiatang on Expression of Gal-3 in Rats After Myocardial Infarction / 中国实验方剂学杂志

Objective:To observe the effect of Gualou Xiebai Banxiatang（GXBT） on cardiac function and myocardial fibrosis in rats after myocardial infarction. Method:The 36 male SD rats were randomly divided into blank group, sham group and surgical group, and 6 males in blank group and sham operation group. The model of phlegm obstruction in myocardial infarction of rats was replicated by ligation of left anterior descending coronary artery and high fat diet, and the successful rats were randomly divided into 3 groups: model group, GXBT group and acertil group. In the sham group, only the threading was not ligated. The blank group and the sham group and the model group were given 10 mL·kg-1·d-1 of normal saline, and 2.68 g·kg-1·d-1 of the GXBT group were given intragastric administration，and 0.36 mg·kg-1·d-1 was given intragastrically in acertil group. After 4 weeks of model, the heart function was detected by heart ultrasound to verify the success of the model. After 8 weeks, the heart function of the heart of the rat was detected by heart ultrasound again, and then the samples were sacrificed. The pathological changes of the myocardial cells of the rats were observed with hematoxylin-eosin(HE) staining， and the degree of myocardial fibrosis in the rats was observed by Masson staining. The changes of serum B-type natriuretic peptide (BNP) and galectin-3 (Gal-3) in rat serum were detected by enzyme-linked immunosorbent assay（ELISA） method, and the expression of Gal-3, Collagen Ⅰ (Col-Ⅰ) and Collagen Ⅲ (Col-Ⅲ) was detected by Western blot. Result:Compared with blank group and sham group, the left ventricular ejection fraction (EF) and short-axis shortening rate (FS) of model group were significantly decreased (P<0.01)， the infiltration of inflammatory cells, the increase of the myocardial collagen fibers, the contents of BNP and Gal-3 in the serum were increased (P<0.05). The expression of Gal-3,Col-Ⅰ and Col-Ⅲ in the myocardial tissue increased significantly (P<0.01). Compared with the model group, EF and FS of GXPD were significantly increased (P<0.05), the morphological structure of myocardial cells was improved, the collagen fiber was decreased. The expression of BNP and Gal-3 in serum decreased significantly (P<0.05), and the content of Gal-3, Col-Ⅰ and Col-Ⅲ in myocardial tissue was decreased (P<0.05). Conclusion:Gualou Xiebai Banxiatang can improve cardiac function, reduce myocardial fibrosis and slow down the process of heart failure after myocardial infarction in rats with myocardial infarction. Its mechanism may be related to the decrease of Gal-3 expression.

Recent advance in association of galectin-3 with / 上海交通大学学报（医学版）

Atrial fibrillation is a common cardiac arrhythmia encountered closely related to structural remodeling such as atrial fibrosis. Galectin-as a biomarker of fibrosis; therefore, it may be involved in atrial remodeling association of Gal-3 with atrial fibrillation.