Galectin-3 Research Articles

Galectin 3 for the diagnosis of bladder cancer

ObjectiveTo evaluate serum levels of galectin-3 (G-3) in patients with bladder cancer and a control group, as a potential diagnostic and prognostic serum tumour marker. Patients and methodsBetween November 2012 and January 2013, 55 patients (median age 58years) were enrolled into three groups, i.e., a control, those with transitional cell carcinoma (TCC) or those with squamous cell carcinoma (SCC). The serum G-3 level was measured the night before cystoscopy. The levels of G-3 levels were correlated with tumour type, stage and grade, and in relation to levels in normal urothelium. The results were analysed statistically using the Mann–Whitney U-test, the Kruskal–Wallis test and the receiver operating characteristic curve, as appropriate. ResultsThe median serum G-3 level was 100, 720 and 920pg/mL in the control, TCC and SCC groups, respectively, with very significantly greater G-3 levels in both the TCC and SCC groups than in the control group. Patients with high-grade TCC had a statistically significantly greater serum G-3 level than those with low-grade tumours, as did those with muscle-invasive TCC than those with Ta tumours. ConclusionsThe level of G-3 can aid as a diagnostic marker in patients with either TCC or SCC of the bladder, but the prognostic significance of G-3 remains to be confirmed.

Construction and identification of the recombinant adenovirus vector pAdxsi-GFP-Galectin-1

Objective To construct and identify the recombinant adenovirus vector pAdxsi-GFP-Galectin-1.Methods Whole sequence of galectin-1 was obtained from original plasmid double-digested with Kpn I/BamH I enzymes.Then Galectin-1 DNA segments were linked into pShuttle-CMV-EGFP vector to obtain recombinant pShuttle-GFP-Galectin-1 plasmid.Next,recombinant DNA sequences CMV-GFP-Galectin1were double-digested with I-Ceu I/I-Sce I enzymes and constructed into pShuttle-GFP-Galectin-1 vector to establish recombinant adenovirus vector pAdxsi-GFP-Galectin-1.Results Through endonuclease and gene sequencing the target gene was verified to be corrrctly cloned in adenvrius vector.Conclusion The recombinant adenovirus vector pAdxsi-GFP-Galectin-1 was successfully constructed. Key words: Recombinant adenovirus vector; Galectin-1

The Emerging Role of Galectin-3 and ST2 in Heart Failure: Practical Considerations and Pitfalls Using Novel Biomarkers

Heart failure (HF) is a leading cause of morbidity and mortality worldwide and, despite recent advances in therapy HF hospitalization rates remains unacceptably high. Prompt identification and optimal management of HF can affect long-term outcome. A valuable tool with diagnostic, prognostic, and treatment-guiding properties in this respect will be very useful, as exemplified by natriuretic peptides. However, natriuretic peptide levels show biological variation and are dependent on age, renal function, and body mass index. Recent advances in the field of molecular biology and HF pathophysiology have led to the discovery of other novel biomarkers that may have advantages. Among others, Galectin-3 (GAL3) and sST2 are 2 promising biomarkers that have been recently developed and can be used alone or in combination with natriuretic peptides in clinical practice. In the current paper, we review the existing data regarding GAL3 and sST2 in HF.

Influence of small interfering RNA-mediated inhibiting human runt-related transcription factor 2 and Galectin-3 gene on proliferation and apoptosis of glioma cell U251

Objective To explore the expression of human runt-related transcription factor 2 (Runx2) and Galectin-3 in glioma cell U251,and to elucidate the influnce of small interfering RNA (siRNA)-mediated inhibiting Runx2 and Galectin-3 gene on proliferation and apoptosis of glioma cell U251.Methods U251 cells were treated with siRNA,then the expression of Runx2 and Galectin-3 mRNA and protein was detected by using reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting respectively.The change in cell proliferation was studied by methyl thiazol tetrazolium (MTT) assay.Cell apoptosis was examined by using flow cytometry (FCM).Results When U251 cells were treated with Runx2-tarted siRNA,the expression of Runx2 (0.260 ± 0.074) and Galectin-3 (0.170 ± 0.065) in mRNA and protein leveld was reduced brokendown,but when the U251 cells were treated with Galectin-3 siRNA,only Galectin-3 expression was decreased in mRNA and protein levels,and the expression of Runx2 had no significant change (P ＜ 0.01).The decrease of Runx2 and Galectin-3 expression resulted in the decrease of U251 cell proliferation activity (P ＜0.01).The apoptosis rate in Runx2,and Galectin-3 siRNA groups was increased (P ＜ 0.01).Conclusion Runx2 and Galectin-3 are expressed in glioma cell U251,and Runx2 mediates the expression of Galectin-3.Down-regulation of both Runx2 and Galectin-3 can suppress proliferation activity and induce apoptosis of U251 cells.Both Runx2 and Galectin-3 may be implicated in tumorigenesis and tumor progression of glioma. Key words: Glioma; Small interfering RNA ; Runt-related transcription factor 2 ; Galectin-3

The radiological and histopathological differential diagnosis of chordoid neoplasms in skull base

Background Chordoid neoplasms refer to tumors appearing to have histological features of embryonic notochord, which is characterized by cords and lobules of neoplastic cells arranged within myxoid matrix. Because of radiological and histological similarities with myxoid matrix and overlapping immunohistochemical profile, chordoma, chordoid meningioma, chordoid glioma, and rare extraskeletal myxoid chondrosarcoma enter in the radiological and histological differential diagnosis at the site of skull base. However, there is always a great challenge for histopathologists to make an accurate diagnosis when encountering a chordoid neoplasm within or near the central nervous system. The aim of this study is to investigate and summarize the radiological, histological features and immunohistochemical profiles of chordoid neoplasms in skull base, and to find a judicious panel of immunostains to unquestionably help in diagnostically challenging cases. Methods A total of 23 cases of chordoid neoplasms in skull base, including 10 chordomas, 5 chordoid meningiomas, 3 chordoid gliomas and 5 extraskeletal myxoid chondrosarcomas, were collected from the First Affiliated Hospital, Sun Yat-sen University and Guangdong Tongjiang Hospital. MRI examination was performed on the patients before surgical treatment. Microscopical examination and immunohistochemical staining study using vimentin (Vim), pan-cytokeratin (PCK), epithelial membrane antigen (EMA), S-100 protein (S-100), glial fibrillary acidic protein (GFAP), D2-40, Galectin-3, CD3, CD20, Ki-67 were performed on the samples of cases. The clinicopathological data of the patients was also analyzed retrospectively. Results Most of chordomas were localized in the clivus with heterogeneous hyperintensity on T2WI scanning. The breakage of clivus was observed in most cases. Histologically, the tumor cells of chordoma exhibited bland nuclear features and some contained abundant vacuolated cytoplasm (the so-called physaliferous cells) within myxoid matrix. Areas of cartilage presented in individual cases. The tumor cells of chordoma were diffusely immuno-positive for PCK and EMA. Chordoid meningioma is characterized by a homogeneous contrast-enhancing mass with dural tail sign. The epithelioid cells were arranged in cords and clusters within a myxoid matrix, which was highly reminiscent of chordoma. The ratio of myxoid component and conventional meningioma was different in tumors. EMA was detectable in all chordoid meningiomas, and 4/5 cases were positive for D2-40. That was a finding which was helpful in distinguishing chordoid meningioma from chordoma. Chordoid gliomas were localized in the third ventricle with homogeneous enhancement on MRI examination. The tumors were composed of clusters and cords of epithelioid tumor cells within a variably mucinous stroma containing lymphoplasmacytic infiltratation. The most distinctive immunohistochemical feature of chordoid gliomas is their strong diffuse reactivity for GFAP. EMA and PCK positive expression can also be seen focally in individual cases. Although extraskeletal myxoid chondrosarcomas share the similar radiological and histological appearance with chordoma, all chondrosarcomas in the present study are completely negative for epithelial markers except for immuno-positivity of S-100 focally. In addition, Galectin-3 can be detected in most of chordoid neoplasms in skull base. Conclusion The specific localization and MRI features of tumors are useful diagnostic clues for the differential diagnosis of chordoid neoplasms in skull base. However, combining with histological features, a panel of selected immunostains, including PCK, EMA, GFAP, S-100 and D2-40, is helpful in making an accurate diagnosis for those diagnostically challenging cases which usually appear to have atypical radiological features or in an unusual site. Ki-67 index and Galectin⁃3 are not recommended to use as diagnostic markers for chordoid neoplasms of skull base because of their less neoplastic specificity.

Expression and prognostic value of galectin-9 in hepatocellular carcinoma patients

To explore the prognostic value of galectin-9 in patients with hepatocellular carcinoma (HCC). Galectin-9 was validated by immunohistochemisty in tissue microarrays from HCC patients (n = 147) and statistically assessed for the prognosis. The serum levels of galectin-9 from another independent cohort including HCC patients (n = 31) were assessed by enzyme-linked immunosorbent assay (ELISA). Patients with a lower expression of galectin-9 had significantly worse prognosis than those with a higher expression. The serum level of galectin-9 of HCC patients (8.36 ± 2.12) µg/L was significantly lower than that in healthy (4.62 ± 1.59 )µg/L and liver cirrhosis controls (5.11 ± 1.92 )µg/L (P < 0.05). Multivariate Cox proportional hazard analysis showed that galectin-9 was an independent marker for predicting a poor prognosis of HCC patients. Involved in the poor prognosis of HCC patients, galectin-9 may be a new predictor of recurrence for HCC patients and serve as a high-priority therapeutic target.

Galectin-3 is an emerging biomarker of heart failure

Galectin-3 (gal-3),a member of the galectin family,is directly associated with cardiac fibrosis and cardiac remodeling.Recently it has been approved by the US Food and Drug Administration as a prognostic aid in patients with heart failure (HF).Gal-3 is associated with age,kidney function and B-type natriuretic peptide (BNP).Compared with the diagnostic utility of BNP,the long-term prognosis value of gal-3 is higher than the value of diagnosis.Higher concentration of Gal-3,a marker of cardiac fibrosis,is associated with increased risk for incident CHF and mortality.(Chin J Lab Med,2013,36:506-510) Key words: Heart failure; Galectin 3; Biological markers

Galectin-1 (GAL-1) expression is a useful tool to differentiate between small cell osteosarcoma and Ewing sarcoma

Galectin-1 (GAL-1) is frequently expressed in osteosarcomas. Although a valuable diagnostic marker to differentiate between chondroblastic osteosarcomas and conventional chondrosarcomas, it has not been tested in the Ewing sarcoma family of tumors (ESFTs). We studied by immunohistochemistry GAL-1 expression in 43 osteosarcomas, 23 chondrosarcomas, and 217 genetically confirmed ESFTs using a tissue microarray. GAL-1 was expressed in 78 % of osteosarcomas, 33 % of chondrosarcomas, and 8 % of ESFTs. Osteoblastic and small cell osteosarcoma subtypes expressed GAL-1 in a high percentage of cells when compared with the other histological subtypes, whereas two chondroblastic osteosarcomas were negative. GAL-1 was mainly expressed in high-grade chondrosarcomas (grade III). ESFTs were rarely positive (8 %), and this was not related to the histological subtype nor to the clinical outcome. Although GAL-1 expression distinguishes chondroblastic osteosarcomas from conventional chondrosarcomas and is usually negative in conventional chondrosarcomas, the final diagnosis needs to incorporate histopathology since some chondroblastic osteosarcomas fail to express GAL-1, while high-grade chondrosarcomas are GAL-1 positive. Since GAL-1 is frequently expressed in osteogenic tumors, including small cell osteosarcoma, but rarely positive in ESFTs, its expression seems a valuable tool for distinguishing between these lesions. GAL-1 immunoexpression is not indicative of prognosis in ESFT.

GDNF promotes neurite outgrowth and upregulates galectin-1 through the RET/PI3K signaling in cultured adult rat dorsal root ganglion neurons

Galectin-1 (GAL-1), a member of a family of β-galactoside binding animal lectins, is predominantly expressed in isolectin B4 (IB4)-binding small non-peptidergic (glial cell line-derived neurotrophic factor (GDNF)-responsive) sensory neurons in the sections of adult rat dorsal root ganglia (DRG), but its functional role and the regulatory mechanisms of its expression in the peripheral nervous system remain unclear. In the present study, both recombinant nerve growth factor (NGF) and GDNF (50ng/ml) promoted neurite outgrowth from cultured adult rat DRG neurons, whereas GDNF, but not NGF, significantly increased the number of IB4-binding neurons and the relative protein expression of GAL-1 in the neuron-enriched culture of DRG. The GAL-1 expression in immortalized adult rat Schwann cells IFRS1 and DRG neuron-IFRS1 cocultures was unaltered by treatment with GDNF, which suggests that GDNF/GAL-1 signaling axis is more related to neurite outgrowth, rather than neuron-Schwann cell interactions. The GDNF-induced neurite outgrowth and GAL-1 upregulation were attenuated by anti-GDNF family receptor (RET) antibody and phosphatidyl inositol-3′-phosphate-kinase (PI3K) inhibitor LY294002, suggesting that the neurite-outgrowth promoting activity of GDNF may be attributable, at least partially, to the upregulation of GAL-1 through RET-PI3K pathway. On the contrary, no significant differences were observed between GAL-1 knockout and wild-type mice in DRG neurite outgrowth in the presence or absence of GDNF. Considerable immunohistochemical colocalization of GAL-3 with GAL-1 in DRG sections and GDNF-induced upregulation of GAL-3 in cultured DRG neurons imply the functional redundancy between these galectins.

Plasma galectin-3 is associated with near-term rehospitalization in heart failure

Plasma galectin-3 is associated with near-term rehospitalization in heart failure

Changes in galectin-3 levels over time predict mortality and morbidity in heart failure

Changes in galectin-3 levels over time predict mortality and morbidity in heart failure

Serum biomarkers of papillary thyroid cancer

ObjectiveTo identify serum biomarkers of papillary thyroid cancer.MethodsProspective analysis was performed of banked tumor and serum specimens from 99 patients with thyroid masses. Enzyme-linked immunosorbent assay (ELISA) was employed to measure levels of five serum proteins previously demonstrated to be up-regulated in papillary thyroid cancer (PTC): angiopoietin-1 (Ang-1), cytokeratin 19 (CK-19), tissue inhibitor of metalloproteinase-1 (TIMP-1), chitinase 3 like-1 (YKL-40), and galectin-3 (GAL-3). Serum levels were compared between patients with PTC and those with benign tumors.ResultsA total of 99 patients were enrolled in the study (27 men, 72 women), with a median age of 54 years. Forty-three patients had PTC and 58 cases were benign tumors. There were no statistically significant differences when comparing all five different biomarkers between PTC and other benign thyroid tumors. The p-values were 0.94, 0.48, 0.72, 0.48, and 0.90 for YKL-40, Gal-3, CK19, TIMP-1, and Ang-1, respectively.ConclusionSerum levels of four of the five proteins were elevated in patients with thyroid masses relative to normal values. However, the difference between benign and PTC was not significant. Two of the markers (Gal-3 & TIMP-1) displayed a greater potential difference, which may warrant further investigation. This study suggests that other serum markers should be sought. This is the first study to investigate potential serum biomarkers based on over-expressed proteins in thyroid cancer versus benign pathology.

Effects of galectin-3 on proliferation of endothelial Tip cells derived from stem cells

Objective To observe the effects of Galectin-3 on proliferation of endothelial Tip cells derived from stem cells.Methods The cultured peripheral blood endothelial progenitor cells in vitro were isolated and purified from human peripheral blood,and the cells were induced to differentiate into endothelial Tip cells.Then,the cells were cultured with Galectin-3 (0,0.1,1.0,2.5,5.0,10.0 mg/L) for24 h.The proliferation of endothelial Tip cells derived from peripheral blood endothelial progenitor cells was measured by using methyl thiazol tetrazolium (MTT) assay.Results The absorbance (A) values in Galectin-3 groups (0.0,0.1,1.0,2.5,5.0,10.0 mg/L) were (0.103 ±0.068),(0.122 ±0.027),(0.139 ±0.023),(0.289 ±0.042),(0.912 ±0.146),and (1.188 ±0.337) respectively.The A values in Galectin-3 (5.0 and 10.0 mg/L) groups were significantly higher than in galectin-3 (0,0.1,1.0and 2.5 mg/L) groups,P ＜ 0.05.There was significant difference in the A values between 5.0 mg/Lgroup and 10.0 mg/L group,P ＜ 0.05.Conclusion Galectin-3 can promote the proliferation of endothelial Tip cells derived from stem ceils. Key words: Stem cell; Endothelial cells ; Galectin-3 ; Proliferations

Structural Basis for Galectin-1-dependent Pre-B Cell Receptor (Pre-BCR) Activation

During B cell differentiation in the bone marrow, the expression and activation of the pre-B cell receptor (pre-BCR) constitute crucial checkpoints for B cell development. Both constitutive and ligand-dependent pre-BCR activation modes have been described. The pre-BCR constitutes an immunoglobulin heavy chain (Igμ) and a surrogate light chain composed of the invariant λ5 and VpreB proteins. We previously showed that galectin-1 (GAL1), produced by bone marrow stromal cells, is a pre-BCR ligand that induces receptor clustering, leading to efficient pre-BII cell proliferation and differentiation. GAL1 interacts with the pre-BCR via the unique region of λ5 (λ5-UR). Here, we investigated the solution structure of a minimal λ5-UR motif that interacts with GAL1. This motif adopts a stable helical conformation that docks onto a GAL1 hydrophobic surface adjacent to its carbohydrate binding site. We identified key hydrophobic residues from the λ5-UR as crucial for the interaction with GAL1 and for pre-BCR clustering. These residues involved in GAL1-induced pre-BCR activation are different from those essential for autonomous receptor activation. Overall, our results indicate that constitutive and ligand-induced pre-BCR activation could occur in a complementary manner.

Epigenetic Regulation of Galectin-3 Expression by β1 Integrins Promotes Cell Adhesion and Migration

Introduction of the integrin β1- but not the β3-subunit in GE11 cells induces an epithelial-to-mesenchymal-transition (EMT)-like phenomenon that is characterized by the loss of cell-cell contacts, cell scattering, increased cell migration and RhoA activity, and fibronectin fibrillogenesis. Because galactose-binding lectins (galectins) have been implicated in these phenomena, we investigated whether galectins are involved in the β1-induced phenotype. We examined 9 galectins and, intriguingly, found that the expression of galectin-3 (Gal-3) is specifically induced by β1 but not by β3. Using β1-β3 chimeric integrins, we show that the induction of Gal-3 expression requires the hypervariable region in the extracellular domain of β1, but not its cytoplasmic tail. Furthermore, Gal-3 expression does not depend on RhoA signaling, serum factors, or any of the major signal transduction pathways involving protein kinase C (PKC), p38 mitogen-activated protein kinase (p38MAPK), extracellular signal-regulated kinase-1/-2 (ERK-1/2), phosphatidylinositol-3-OH kinase (PI3-K), or Src kinases. Instead, Gal-3 expression is controlled in an epigenetic manner. Whereas DNA methylation of the Lgals3 promoter maintains Gal-3 silencing in GE11 cells, expression of β1 causes its demethylation, leading to transcriptional activation of the Lgals3 gene. In turn, Gal-3 expression enhances β1 integrin-mediated cell adhesion to fibronectin (FN) and laminin (LN), as well as cell migration. Gal-3 also promotes β1-mediated cell adhesion to LN and Collagen-1 (Col)-1 in cells that endogenously express Gal-3 and β1 integrins. In conclusion, we identify a functional feedback-loop between β1 integrins and Gal-3 that involves the epigenetic induction of Gal-3 expression during integrin-induced EMT and cell scattering.

B Cell Development and the Splenic Microenvironment in Dlk-1 Deficient Mice

AbstractAbstract 1251 Background:DLK-1 is a transmembrane and secreted protein that plays a crucial role in normal B cell development and differentiation. In a previous study we showed that DLK-1 knockout mice (Dlk1−/− mice (KO)) have distinct differences in B cell fractions in the spleen and bone marrow compared to wild-type Dlk1+/+ (WT) mice. KO mice showed a decrease in follicular (FO) B cells and an increase in the size of the marginal zone (MZ) and number of MZ B cells in the spleen of 8 week old mice. Furthermore, there was an exaggerated primary T-dependent antigen-specific humoral immune response. The mechanisms underlying the changes in splenic B cell fractions between KO and WT mice are not yet clear. It has been suggested that stromal microenvironmental cells form distinct cellular niches that influence different stages of B cell development. Alterations in these stromal niches due to absence of DLK-1 may be an underlying cause of the observed splenic B cell fraction alterations. It was previously shown that Galectin-1 (GAL1) plays an important role in the bone marrow microenvironment and affects proliferation and differentiation of normal mouse pre-BII cells (Blood April 21, 2011). This study is designed to investigate the splenic stromal cells in DLK-1 deficient mice as a step toward understanding these B cell alterations, and to test whether the stromal cell derived-GAL1 influences splenic B-cell development. Methods:For detection of B cell fractions, a multicolor flow cytometry panel consisting of anti-IgD/IgM/CD23/CD93/CD45R/CD21/CD35 was used. B cell fractions were identified as follows: MZ (CD23neg-low, CD21high), FO (CD23high, CD21intermediate), Tr1 (CD23neg, CD21neg, AA4.1pos, B220pos), Tr2 (CD23pos, AA4.1pos, B220pos). For detection of stromal cell fractions, an anti-CD11c/Ter119/CD19/Gr-1/Tie-2/CD45/CD31/CD117/CD34 panel was used. Stromal cells were identified as follows: CD45neg, lineage− (Ter119, CD19, GR1, CD11c, and CD34), CD117neg, CD34neg, Tie2neg. Two stromal cell fractions were detected: CD31 +and CD31−. Galectin-1 expression was evaluated on CD31+ and CD31−stroma cell fractions. An eight color flow cytometric panel consisting of antibody directed to MHC II, CD11c, Gr-1, CD8a, B220, and CD11b was used to evaluate myeloid, lymphoid and plasmacytoid dendritic cell fractions. Results:Our data showed an increase in MZ B-cells (p<0.005) and a decrease in FO B cells (p<0.005) in the KO mice. When looking at the splenic stromal cells, we found an increase in the CD31+ fraction and a decrease in the CD31- fraction in KO mice compared to WT mice (p<0.005). We observed that the CD31 + stromal cell expressed high galectin-1 (GAL1) levels compared to CD31− stroma cells. Also there was an increased percentage of myeloid dendritic cells in KO compared to WT (p< 0.05). Conclusion:We have shown that absence of DLK-1 leads to alterations in splenic stromal populations and that these may play an important role in altered B cell populations and function observed in DLK-1-deficient mice. We are investigating whether the CD31+ GAL1 +stroma cell is a key stroma cell that plays a critical role in splenic B cell development and is responsible for the B-lineage differences seen in DLK-1-deficient mice. Our observation that there is an increase in the myeloid dendritic cell fraction may explain the exaggerated primary immune response seen in the KO mice. These data show that DLK-1-deficiency leads to several changes in the splenic cellular microenvironment and suggest that these changes contribute to alterations in B-cell development and function. Disclosures:No relevant conflicts of interest to declare.

Anti-EGFR/Radiation Therapy Enhanced Through Galectin-1 Suppression in NSCLC

Anti-EGFR/Radiation Therapy Enhanced Through Galectin-1 Suppression in NSCLC

A Genome-Wide Association Study of Circulating Galectin-3

Galectin-3 is a lectin involved in fibrosis, inflammation and proliferation. Increased circulating levels of galectin-3 have been associated with various diseases, including cancer, immunological disorders, and cardiovascular disease. To enhance our knowledge on galectin-3 biology we performed the first genome-wide association study (GWAS) using the Illumina HumanCytoSNP-12 array imputed with the HapMap 2 CEU panel on plasma galectin-3 levels in 3,776 subjects and follow-up genotyping in an additional 3,516 subjects. We identified 2 genome wide significant loci associated with plasma galectin-3 levels. One locus harbours the LGALS3 gene (rs2274273; P = 2.35×10−188) and the other locus the ABO gene (rs644234; P = 3.65×10−47). The variance explained by the LGALS3 locus was 25.6% and by the ABO locus 3.8% and jointly they explained 29.2%. Rs2274273 lies in high linkage disequilibrium with two non-synonymous SNPs (rs4644; r2 = 1.0, and rs4652; r2 = 0.91) and wet lab follow-up genotyping revealed that both are strongly associated with galectin-3 levels (rs4644; P = 4.97×10−465 and rs4652 P = 1.50×10−421) and were also associated with LGALS3 gene-expression. The origins of our associations should be further validated by means of functional experiments.

Galectin 3 complements BNP in risk stratification in acute heart failure

Background: Galectin 3 (G3) is a mediator of fibrosis and remodeling in heart failure.Methods: Patients diagnosed with and treated for Acute Heart Failure Syndromes were prospectively enrolled in the Decision Making in Acute Decompensated Heart Failure multicenter trial.Results: Patients with a higher G3 had a history of renal disease, a lower heart rate and acute kidney injury. They also tended to have a history of HF and 30-day adverse events compared with B-type natriuretic peptide.Conclusion: In Acute Heart Failure Syndromes, G3 levels do not provide prognostic value, but when used complementary to B-type natriuretic peptide, G3 is associated with renal dysfunction and may predict 30-day events.

The increased express of TIM-1, TIM-3 and other association genes in peripheral blood mononuclear cells from patients with Graves disease

Objective To detect the levels of the mRNA expression of TIM-3,TIM-1,T-bet,GATA-3,IFN-γ,IL-4 and Galectin-9 in the peripheral blood monocytes (PBMCs) of the patients with Graves disease(GD),and to explore their potential role in the pathogenesis of GD.Methods We used fluorescence quantitative real-time reverse transcription-polymerase chain reaction to measure the mRNA expression of TIM-3,TIM-1 and other associated genes in PBMCs of 70 patients with GD and 22 healthy controls.In addition,we analyzed the relationship of TIM-3,TIM-1 and other associated genes.Results The expression of TIM-3 and TIM-1 mRNA in the PBMCs from GD patients were abnormally higher,the GD patients with Graves' ophthalmopathy group had significantly higher level of TIM-3 mRNA expression than that of GD patients without Graves' ophthalmopathy group,but no statistically significant difference was found in the expression of TIM-1 mRNA.Untreated GD patients had significantly higher level of TIM-3 mRNA expression than that of GD patients in recurrence group,however the expression of TIM-1 mRAN was opposite.But no statistically significant difference was found in TIM-3 mRNA expression of recovery GD patient and healthy control group.Though the expression of TIM-1 mRNA was significantly decreased,it was still higher than that of the normal control group.Conclusion TIM-3 and TIM-1 may participate in the occurrence,development and turnover of GD.TIM-3 or TIM-1 may prove to be an important target for developing new drugs and treatments to GD. Key words: Graves disease; TIM-3; TIM-1; Th1/Th2