Research advances in the immunomodulatory mechanism of galectin-9 and its role in liver diseases / 临床肝胆病杂志

Galectin-9 （Gal-9） is a member of the galectin family that can specifically recognize and bind to galactosides. Recent studies have shown that Gal-9 is highly expressed in the liver and can help to maintain intrahepatic immune homeostasis and perform biological functions in various liver diseases. This article reviews the immunomodulatory functions of Gal-9 and its role in different liver diseases. Studies have shown that Gal-9 has important biological functions in different liver diseases through multiple pathways. Research on the specific immunomodulatory mechanisms and functions of Gal-9 may help to discover the therapeutic role of Gal-9 in liver diseases.

Targeting stroma and tumor, silencing galectin 1 treats orthotopic mouse hepatocellular carcinoma

This study examines inhibiting galectin 1 (Gal1) as a treatment option for hepatocellular carcinoma (HCC). Gal1 has immunosuppressive and cancer-promoting roles. Our data showed that Gal1 was highly expressed in human and mouse HCC. The levels of Gal1 positively correlated with the stages of human HCC and negatively with survival. The roles of Gal1 in HCC were studied using overexpression (OE) or silencing using Igals1 siRNA delivered by AAV9. Prior to HCC initiation induced by RAS and AKT mutations, lgals1-OE and silencing had opposite impacts on tumor load. The treatment effect of lgals1 siRNA was further demonstrated by intersecting HCC at different time points when the tumor load had already reached 9% or even 42% of the body weight. Comparing spatial transcriptomic profiles of Gal1 silenced and OE HCC, inhibiting matrix formation and recognition of foreign antigen in CD45+ cell-enriched areas located at tumor-margin likely contributed to the anti-HCC effects of Gal1 silencing. Within the tumors, silencing Gal1 inhibited translational initiation, elongation, and termination. Furthermore, Gal1 silencing increased immune cells as well as expanded cytotoxic T cells within the tumor, and the anti-HCC effect of lgals1 siRNA was CD8-dependent. Overall, Gal1 silencing has a promising potential for HCC treatment.

The immunohistochemical Galectin-3 expression in tumor and cancer-associated fibroblasts in invasive ductal carcinomas of breast and their relationship with clinicopathological parameters

Background: Galectin-3 has an important role in metastasis, therefore, Galectin-3-focused therapies have attracted attention for various cancers. Aim: We aimed to reveal the relationship between the expression of Galectin-3 within the tumor/cancer-associated fibroblasts (CAF) and clinicopathological parameters in patients with invasive ductal carcinomas. Materials and Methods: Hematoxylin and eosin-stained slides of breast excision materials diagnosed between 2010 and 2016 were re-examined retrospectively. Accordingly, 118 cases (luminal group = 58, Human epidermal growth factor receptor 2 (HER2) group = 27, and triple-negative breast carcinoma group [TNBC] =33 cases) were included. Galectin-3 levels were evaluated with a calculated H-score in tumor and semiquantitatively in CAFs. Statistical Analysis: Data was analyzed with t-tests and Chi-square tests. Kaplan–Meier and Log-rank tests were used for survival analysis. Results: The presence of Galectin-3 expression in CAFs but not in the tumor was associated with the greater number of axillary metastatic nodes and advanced pN stage. The loss of Galectin-3 expression in CAFs was more frequent in TNBC. There was no significant relationship between the expression level of Galectin-3 and survival status. However, in most of the cases with distant metastasis or patients who died, Galectin-3 was negative in the tumor, whereas it was positive in CAFs. Conclusions: The expression of Galectin-3 in tumors and CAFs may have a role in metastasis to axillary lymph nodes and distant sites. In terms of molecular subtype, TNBCs show a relationship with Galectin-3 negativity in CAFs.

The level of Tim-3+CD8+ T cells can serve as a potential marker for evaluating the severity of acute graft-versus-host disease after haplo-PBSCT

Early and accurate diagnosis of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation is crucial for the prognosis of patients. This study identified a potential biomarker for the severity of aGVHD after human leukocyte antigen (HLA)-haploidentical peripheral blood hematopoietic stem cell transplantation (haplo-PBSCT). We included 20 healthy subjects and 57 patients who underwent haplo-PBSCT. Of these patients, 22 developed aGVHD after haplo-PBSCT. The results showed that patients with aGVHD had significantly increased levels of Tim-3+/Perforin+/Granzyme B+CD8+ T cells, but significantly decreased Galectin-9. The differences in Galectin-9 and Tim-3+/Granzyme B+CD8+ T cells between grade I-II aGVHD and III-IV aGVHD were also significant. In vitro, the apoptosis of CD8+ T cells from aGVHD patients was significantly increased after Tim-3/Galectin-9 pathway activation, which decreased Granzyme B secretion. As revealed by univariate analysis, the level of Tim-3+CD8+ T cells was a risk factor for severe aGVHD. ROC analysis demonstrated that high levels of Tim-3+CD8+ T cells had a significant diagnostic value for severe aGVHD, with an area under the curve of 0.854 and cut-off value of 14.155%. In conclusion, the binding of Tim-3 with exogenous Galectin-9 can promote apoptosis of CD8+ T cells and affect the secretion of Granzyme B. Tim-3+CD8+ T cells have the potential to serve as immunological markers for assessing the severity of aGVHD after haplo-PBSCT and identifying patients at a higher risk for severe aGVHD.

Serum galectin-3 levels predict poor prognosis in sepsis and septic shock patients

SUMMARY OBJECTIVE: Sepsis and septic shock are clinical conditions with high mortality and an ever-increasing prevalence, and early diagnosis is of great importance in treating these diseases. Increase in serum Galectin-3 protein in septic patients is associated with increased inflammation, which in turn is associated with mortality. This study aimed to investigate the diagnostic importance of serum Galectin-3 levels and its relationship with in-hospital mortality in sepsis and septic shock patients. METHODS: This prospective cohort study included 44 sepsis and 44 septic shock patients. Sequential Organ Failure Assessment score and Acute Physiology and Chronic Health Evaluation 2 score were calculated. In addition, routine clinical and laboratory parameters along with serum Galectin-3 were evaluated. RESULTS: Serum Galectin-3 levels were significantly higher in the septic shock group [4.1 (0.1-10.2) vs. 6.0 (0.1-11.3) ng/mL, respectively; p=0.01]. Moreover, patients with a Galectin-3 level <6.94 ng/mL were associated with longer survival [31.4 vs. 23.1 days; hazards ratio, 1.85; 1.03-3.34, p=0.03]. More importantly, the need for mechanical ventilation, the duration of mechanical ventilation, and serum Galectin-3 levels were independent prognostic factors and predicted poor in-hospital survival in both sepsis and septic shock patients. CONCLUSION: These findings suggest that Galectin-3 levels are higher in septic shock patients and predict mortality. In addition, high serum Galectin-3 levels, together with mechanical ventilation requirement and mechanical ventilation duration, are closely associated with poor in-hospital survival. Therefore, Galectin-3 may be a valuable diagnostic and prognostic biomarker in these patients.

Establishment and evaluation of in vitro galectin-3 inhibitor screening model / 药学学报

Galectin-3 (Gal-3) belongs to the galectin family and is specific in binding β-galactoside. Through its C-terminal domain, Gal-3 binds to the galactoside group of the glycosylated insulin receptor (IR) and inhibits IR signaling pathway, which leads to the insulin resistance. Thus, Gal-3 is a potential therapeutic target for the treatment of insulin resistance and type 2 diabetes. Here we report a simple Gal-3 screening model based on the property that Gal-3 binds to the galactoside. We expressed and purified human Gal-3 in Escherichia coli (E.coli), and labeled it with fluorescein isothiocyanate (FITC) in vitro. After incubating FITC labeled Gal-3 (Gal-3-FITC) with PANC-1 cells, which express glycosylated membrane protein, PANC-1 cells started to show green fluorescent signal due to the Gal-3-FITC binding to the glycosylated membrane protein. Gal-3 inhibitor disrupts the binding of Gal-3-FITC and PANC1 cells, subsequently leads to the decrease of the fluorescent signal in PANC-1 cells. We can evaluate the inhibitory efficiency of Gal-3 inhibitors through measurement of the fluorescent signal. Further studies show this model is simple, stable, and repeatable with a Z' factor between 0.7 and 0.85. In sum, we have successfully established an in vitro high-throughput screening model for Gal-3 inhibitors.

Significance of Tim-3 and Its Ligand Galectin-9 in Th1/Th2 Imbalance in Patients with Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To investigate the significance of Tim-3 and Galectin-9 in Th1/Th2 imbalance in patients with multiple myeloma (MM).@*METHODS@#55 newly diagnosed MM patients and 20 healthy controls were included. Flow cytometry was used to detect the expression of Tim-3 on CD4+T cells, the proportion of Th1, Th2, Tim-3+Th1 and Tim-3+Th2 cells in peripheral blood. ELISA was used to detect the levels of cytokines IFN-γ and IL-4 in serum, and PCR was used to detect the level of Galectin-9 mRNA. Then the correlations between Galectin-9 mRNA expression and Th-cell subsets and related cytokine levels, as well as the relationship between Tim-3+Th1/Tim-3+Th2 ratio and corresponding clinical features were analyzed.@*RESULTS@#Compared with the control group, the expression of Tim-3 on CD4+T cells in peripheral blood of MM patients was significantly increased (P<0.05), the proportions of Tim-3+Th1 cells, Tim-3+Th2 cells and Tim-3+Th1/Tim-3+Th2 ratio in MM patients were also increased (P<0.05), while the proportion of Th1 cells and Th1/Th2 ratio in MM patients were significantly decreased (P<0.05). The level of cytokine IFN-γ and IFN-γ/IL-4 ratio in MM patients were significantly decreased (P<0.05), while the level of cytokine IL-4 was increased (P<0.05). The mRNA levels of Galectin-9 in MM patients were significantly increased (P<0.05). The levels of Galectin-9 mRNA were positively correlated with Tim-3+CD4+T cells (r=0.663), Tim-3+Th2 cells (r=0.492) and IL-4 (r=0.470), while negatively correlated with IFN-γ (r=-0.593). The ratios of Tim-3+Th1/Tim-3+Th2 in MM patients were positively correlated with ISS stage (r=0.511), osteolytic damage (r=0.556) and chromosome abnormality (r=0.632).@*CONCLUSION@#These results suggest that Tim-3 and Galectin-9 are involved in Th1/Th2 imbalance in MM patients, and the high ratio of Tim-3+Th1/Tim-3+Th2 is associated with poor clinical prognosis.

Increased tumor-associated mast cells facilitate thyroid cancer progression by inhibiting CD8+ T cell function through galectin-9

As an important component of solid tumors, mast cells show specific phenotypes in various tumor microenvironments. However, the precise mechanism of mast cell accumulation and the phenotypic features of thyroid cancer (TC) remain largely unknown. Here, we found that mast cells were obviously recruited to tumor tissue by TC-derived stem cell factor (SCF). With tumor progression, mast cell levels increased gradually. In addition, intratumoral mast cells expressed higher levels of the immunosuppressive molecule galectin-9, which effectively suppresses CD8+ T-cell antitumor immunity in vitro. Blocking galectin-9 on tumor-infiltrating mast cells reversed the immunosuppression of CD8+ T cells. In conclusion, our data elucidated novel protumorigenic and immunosuppressive roles of mast cells in TC. In addition, our results indicated that blocking mast cells may impede tumor progression and ameliorate the prognosis of TC patients.

Association of Galectin-3 with atrial fibrillation / 中国综合临床

Objective:To investigate the effect of galactose lectin 3 (Gal-3) on the pathogenesis of atrial fibrillation.Methods:This study adopts a case-control study method. 55 patients with non valvular atrial fibrillation (atrial fibrillation group) admitted to the First People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from February to July 2019 were selected, and another 55 healthy individuals who underwent physical examination at our hospital during the same period were selected as the control group. Compare the general data and levels of various laboratory indicators between two groups, including blood routine, fasting blood glucose, blood lipids, liver and kidney function, and plasma Gal-3. Analyze the influencing factors of atrial fibrillation and the predictive value of plasma Gal-3 levels for the onset of atrial fibrillation. The measurement data with normal distribution and the measurement data converted to normal distribution after taking natural logarithm are expressed in xˉ± s. The comparison between the two groups is performed by independent sample t test; The measurement data of non normal distribution is represented by [ M ( Q1, Q3)], and Wilcoxon signed rank sum test is used for inter group comparison; The counting data is represented by examples (%), and the comparison between groups is conducted using χ 2 test. The influencing factors of atrial fibrillation were analyzed using logistic regression analysis. Results:The age, NLR, and blood creatinine levels in the atrial fibrillation group were higher than those in the control group [(71.16±9.17) years vs (60.71±10.11) years, (2.32±0.85) vs (1.74±0.81), (74.18±21.61) μmol/L vs (64.69±18.30) μmol/L, t-values are 5.68, 3.66, 2.48, P-values are <0.001, <0.001, 0.015], total cholesterol, HDL-C, LDL-C Albumin and eGFR water were on average lower than those in the control group [(4.31±1.67) mmol/L vs (5.13±0.78) mmol/L, (0.96±0.21) mmol/L vs (1.21±0.32) mmol/L, (2.35±0.65) mmol/L vs (3.04±0.62) mmol/L, (39.58±3.83) g/L vs (44.66±5.61) g/L, (94.84±29.22) mL/(min·1.73 m 2) vs (111.77±21.51) mL/(min·1.73 m 2)] ,The t-values are 3.30, 4.87, 5.69, 5.54, 3.46, and the P-values are 0.001,<0.001,<0.001,<0.001, 0.001, respectively. The plasma Gal-3 levels in the atrial fibrillation group were higher than those in the control group [(12.79±4.24)] μg/L vs (7.31±2.28) μg/L], the difference was statistically significant ( t=8.43, P<0.001), and the plasma Gal-3 level in the persistent atrial fibrillation group was higher than that in the paroxysmal atrial fibrillation group [(14.03±3.95) μg/L vs (11.51±4.21) μg/L], the difference was statistically significant ( t=2.29, P=0.026). The results of multivariate logistic regression analysis showed that after excluding other factors, Gal-3 remained an independent influencing factor for atrial fibrillation (odds ratio=1.66, 95% confidence interval: 1.29-2.12, P<0.001). Conclusions:Plasma Gal-3 is an influencing factor for the onset of atrial fibrillation. After excluding other factors, Gal-3 remains an independent influencing factor for atrial fibrillation, with an increase of 1 μg/L in Gal-3 increases the risk of atrial fibrillation by 1.66 times.

Effect of modified citrus pectin on synovial fibroblasts / 国际生物医学工程杂志

Objective:To study the effects of modified citrus pectin (MCP) on the viability and gene expressions of synovial fibroblasts (SF) as well as SF treated by galectin-3 (Gal-3).Methods:Rabbit SF was isolated and cultured in vitro. Then SF was treated with different concentrations of MCP (0, 250, 500, and 750 mg/L). In addition, SF was further treated with the same different concentrations of MCP after treatment with 10 μg/ml Gal-3 for 24 h. The viability of SF was detected by CCK-8 on the first, third, and fifth day after treatment. The mRNA expression of transforming growth factor-β1 (TGF-β1), type I collagen (COL1A2), and Gal-3 in SF was detected by real-time quantitative PCR. The synthesis of type I collagen in SF was investigated by immunofluorescence staining. Results:MCP, especially at a concentration of 500 mg/L can inhibit the proliferation of SF significantly (all P < 0.05) on the first, third, and fifth day after treatment. Compared with the control group, MCP at different concentrations induced different gene expression profiles. In particular, MCP at high concentrations can upregulate the expression of TGF-β1, COL1A2 and Gal-3 in SF. However, MCP shows no significant effect on the synthesis of type I collagen in SF. MCP can down-regulate the expression of TGF-β1, COL1A2, and significantly reduce the synthesis of type I collagen in SF after Gal-3 treatment. Particularly, the effect of MCP at a concentration of 500 mg/L on inhibiting the expression of TGF-β1, COL1A2, and Gal-3 in SF is significant. Conclusions:MCP can inhibit the excessive proliferation of SF and regulate gene expression in SF.

Role of galectin-3 in the early brain injury of mice with subarachnoid hemorrhage is associated with the regulation of microglia polarization / 国际脑血管病杂志

Objective:To investigate the effect of galectin-3 (gal-3) on microglia polarization after subarachnoid hemorrhage (SAH).Methods:C57BL/6 male adult mice were used to induce SAH or sham operation models. Gal-3 siRNA or negative control siRNA was injected into the lateral ventricle 48 h before the model was induced. After 24 h of model preparation, the SAH score, neurological function score, brain water content, and Evans blue exudate were measured. Western blot analysis was used to detect the expressions of M1 phenotypic markers (inducible nitric oxide synthase [iNOS], CD11b, tumor necrosis factor [TNF]-α) and M2 phenotype markers (CD206, YM1/2, arginase-1 [Arg1]).Results:After using Gal-3 siRNA to inhibit Gal-3, the neurological function score significantly increased, while the SAH score, brain water content, and Evans blue exudate significantly decreased ( P<0.001). Western blot analysis showed that the expressions of M1 phenotypic markers (iNOS, CD11b and TNF-α) in microglia were significantly decreased after Gal-3 inhibition, while the expressions of M2 phenotypic markers (CD206, YM1/2 and Arg1) were significantly increased ( P<0.001). Conclusion:Inhibition of Gal-3 expression can alleviate the early brain injury after SAH, and its mechanism may be associated with regulating the polarization of microglia from M1 to M2 phenotype.

Galectin-3 and ischemic stroke / 国际脑血管病杂志

Ischemic stroke is a disease with high incidence, high disability and high mortality rates. As a key regulator of microglia activation and proliferation, galectin-3 may have dual effects on ischemic stroke. This article reviews the structure and function of galectin-3, as well as its roles in ischemic stroke.

Immunohistochemical Evaluation of Galectin?3 Expression in Oral Squamous Cell Carcinoma, Oral Leukoplakia and Normal Mucosa

Background: Galectin 3 (Gal?3) has diverse functions critical in cancer biology including cell proliferation, apoptosis, evasion of immune responses and angiogenesis. The expression of Gal?3 is heterogeneous in normal and neoplastic tissues. In oral squamous cell carcinoma (OSCC) and oral leukoplakia (OL), both increased and decreased expressions of Gal?3 were elicited in numerous studies. Aims: To evaluate, compare and correlate the immunohistochemical expression of Gal?3 in OSCC, OL and normal oral mucosa. Settings and Design: The study was conducted at the Department of Oral Pathology and Microbiology at PMS College of Dental Science and Research, Vattapara, Thiruvananthapuram. This is a retrospective analytical study. Methods and Material: Clinically diagnosed and histopathologically confirmed cases of OSCC (n = 21), OL (n = 21), and normal oral mucosa (n = 21) were included in the study. Paraffin?embedded tissues were subjected to immunohistochemical analysis for Gal?3 expression. Gal?3 staining expression, staining distribution and cellular localisation were evaluated. All sampled categories were compared using immunohistochemical scoring analysis such as the H?score, labelling index (LI), immunoreactive score (IRS) and staining intensity (SI). Statistical Analysis: The results were statistically analysed using multivariate analysis of variance (MANOVA) within and among the groups. Results and Conclusion: The statistical inferences obtained found that the H?score could be used as a guideline for better differentiation between the groups and among the groups. The P value obtained was < 0.0125 and was found to be significant. The observation in our study shows that the immunohistochemical expression of Gal?3 gradually decreased from normal oral mucosa to OL to OSCC.

Expression and significance of serum soluble T cell immunoglobulin-domain and mucin-domain protein-3 and galectin-9 in patients with early acute pancreatitis / 中华消化杂志

Objective:To investigate the expression and significance of serum soluble T cell immunoglobulin-domain and mucin-domain protein-3 (sTIM-3) and galectin-9 (Gal-9) in patients with early acute pancreatitis (AP), so as to provide theoretical and clinical evidence for the early prediction and diagnosis of AP.Methods:From 15 September 2020 to 23 July 2021, a total of 94 AP patients with a time from onset to admission ≤48 h who were admitted to Changzhou No.2 People′s Hospital, Nanjing Medical University were selected, including 42 cases of mild acute pancreatitis (MAP), 35 cases of moderately severe acute pancreatitis (MSAP) and 17 cases of severe acute pancreatitis (SAP). The basic clinical features of AP patients were collected. Acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ), modified computed tomography severity index (MCTSI) and bedside index for severity in acute pancreatitis (BISAP) scores were evaluated in all AP patients. The levels of serum interleukin (IL)-6, IL-10, Gal-9 and sTIM-3 were detected with enzyme linked immunosorbent assay. Kruskal-Wallis test and Mann-Whitney U test were used for statistical analysis. Spearman rank correlation test and Pearson correlation analysis were used to analyze the correlation of sTIM-3, Gal-9 with inflammatory indicators and AP related scoring systems. Receiver operating characteristic curve (ROC) was performed for efficiency analysis of the combination of sTIM-3 and Gal-9 in predicting the severity of AP patients. Results:Serum sTIM-3, Gal-9 and IL-6 levels of SAP patients were higher than those of MAP patients (2 085.00 ng/L (1 628.00 ng/L, 2 673.00 ng/L) vs. 746.10 ng/L (514.50 ng/L, 1 303.00 ng/L); 466.60 ng/L (375.90 ng/L, 629.30 ng/L) vs. 108.10 ng/L (90.29 ng/L, 138.90 ng/L); (323.60±62.93) ng/L vs. (42.90±28.82) ng/L), while IL-10 level was lower than that of MAP patients ((760.30±200.40) ng/L vs. (1 206.00±566.30) ng/L), and the differences were statistically significant ( Z=45.00 and <0.01, t=23.62 and 3.15; all P<0.01). The APACHE Ⅱ and BISAP scores of SAP patients were higher than those of MAP and MSAP patients (12.00(6.00, 16.50) vs. 3.00(2.00, 5.00) and 6.00(3.00, 8.00); 3.00(3.00, 4.00) vs.1.00(1.00, 1.00) and 2.00(2.00, 3.00)), and the MCTSI score was higher than that of MAP patients (4.00(3.00, 6.00) vs. 2.00(0.00, 2.00)), and the differences were statistically significant ( Z=644.50, 704.00, 474.50, 492.50 and 664.00, all P<0.001). Serum sTIM-3 and Gal-9 were positively correlated with the pro-inflammatory factor IL-6 ( r=0.552 and 0.297, P<0.001 and =0.004). Serum sTIM-3 was negatively correlated with the anti-inflammatory factor IL-10 ( r=-0.397, P<0.001). There was no correlation between Gal-9 and the anti-inflammatory factor IL-10 ( P>0.05). Serum sTIM-3 and Gal-9 were positively correlated with APACHE Ⅱ, MCTSI and BISAP scores ( r=0.210, 0.271 and 0.363, P=0.042, =0.008 and <0.001; r=0.390, 0.448 and 0.440, all P<0.001). The areas under ROC curves (95% confidence interval) of serum sTIM-3 and Gal-9 detected alone and in combination was 0.805 (0.716 to 0.895), 0.814 (0.725 to 0.903) and 0.856 (0.773 to 0.939), respectively, and the sensitivity was 69.2%, 67.3%, 75.0%, respectively, and the specificity was 83.3%, 97.6%, 97.6%, respectively. Conclusions:The serum levels of sTIM-3 and Gal-9 increased in patients with early AP and are correlated with the severity of AP. The combined detection of sTIM-3 and Gal-9 has high sensitivity in predicting early AP, and the two indicators may be the reliable predictors of early AP.

Expression of serum galectin-3 in elderly patients with atrial fibrillation and its impact on prognosis / 中华老年医学杂志

Objective:To investigate the expression of serum galectin-3 in elderly patients with or without atrial fibrillation and to explore its impact on the prognosis of patients with atrial fibrillation.Methods:In this retrospective study, 100 patients aged 60 years or older treated at the Department of Geriatric Cardiovascular Medicine, Second Xiangyang Hospital, Central South University between March 2018 and September 2018 were enrolled.Based on electrocardiogram and previous history of atrial fibrillation, 73 participants were assigned to the atrial fibrillation group and 27 patients with sinus rhythm and no history of atrial fibrillation during the same period served as the control group.Elisa kits were used to measure the expression of galectin-3 in both groups, and echocardiography was used to measure the size of each cardiac chamber in patients.The Mann-Whitney test was used to compare galectin-3 levels between the two groups, and binary logistic regression analysis was used to determine risk factors for atrial fibrillation in the elderly.Kaplan-Meier survival curves and Cox proportional risk regression were used to analyze survival and the relationship between galectin-3 and prognosis.Results:Serum galectin-3 levels of patients in the atrial fibrillation group were higher than in the control group[(395.13±113.24)ng/L vs.(328.53±89.11)ng/L, t=2.626, P<0.01]. The level of galectin 3 in participants aged ≥ 65 years(n=48)was higher than in those aged<65 years(n=52), (414.01±105.03)ng/L vs.(343.11±106.01)ng/L( t=2.626, P<0.01). The galectin-3 level had a positive correlation with age( r=0.40, P<0.01), duration of atrial fibrillation( r=0.224, P<0.05)and C-reactive protein( r=0.305, P<0.01), but no correlation with N-terminal pro-B-type natriuretic peptide, atrial or ventricular size and the score of CHA2DS2-VASc in patients with atrial fibrillation, .Galectin-3 was a risk factor in patients with atrial fibrillation( P<0.01). Galectin-3 levels did not affect survival(log-rank=0.990)or prognosis( P>0.05)in patients with atrial fibrillation. Conclusions:Galectin-3 levels in elderly atrial fibrillation patients are higher than in people without atrial fibrillation and are positively correlated with age, duration of atrial fibrillation, and C-reactive protein.Galectin-3 is a risk factor for atrial fibrillation in elderly patients.

Mechanism of tanshinone ⅡA inhibiting myocardial remodeling by Galectin-3 / 中华危重病急救医学

Objective:To explore the effect of tanshinone ⅡA on myocardial remodeling in ischemia/reperfusion (I/R)-induced heart failure of rodent model.Methods:① In vivo, 30 SD rats were randomly divided into sham operation, heart failure and tanshinone ⅡA treatment group, with 10 rats in each group. The I/R model was established by ligating the left coronary artery until ST segment elevation for 30 minutes, then the ligation was removed for 2 hours as reperfusion. In the sham operation group, the rat chest was opened without artery ligation. Three days after model establishment, tanshinone ⅡA (10 mg/kg) were given intraperitoneal injected in tanshinone ⅡA group for 9 weeks. In the other two groups, normal saline was administrated in the same way. The behavioral manifestations of the rats in each group were observed; hemodynamic indexes were evaluated; Masson staining was performed to observe the degree of myocardial fibrosis; enzyme linked immunosorbent assay (ELISA) was used to detect the content of Galectin-3 in myocardial tissue; quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect the expressions of collagenⅢ, collagenⅠ, matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase (TIMP-1). ② In vitro, rats primary cardiac fibroblasts were extracted and isolated, and divided into blank control group, angiotensinⅡ group (7-10 mmol/L angiotensinⅡ) and angiotensinⅡ+ tanshinoneⅡA group (7-10 mmol/L angiotensinⅡ+ 5-10 mmol/L tanshinone ⅡA). At 24 hours and 48 hours of culture, the cell proliferation in each group was detected by methyl thiazolyl tetrazolium (MTT); the expressions of collagenⅢ, collagenⅠ, MMP-2 and TIMP-1 were detected by qRT-PCR; the content of Galectin-3 in cardiac fibroblasts was detected by ELSIA. Results:① In vivo, the rats' activity status, hair conformity and food intake were ranked from good to bad in order of sham operation group, tanshinone ⅡA group and heart failure model group. Compared with the sham-operated group, the heart rate (HR) of the rats in the heart failure model group was significantly decreased and the heart function was significantly impaired. The mRNA and protein expression of collagenⅠ, collagenⅢ, TIMP-1 and Galectin-3 content were significantly increased, while the mRNA and protein expression of MMP-2 were significantly decreased. Compared with the heart failure model group, rats in the tanshinone ⅡA group showed significantly higher HR and improved cardiac function, significantly lower mRNA expression of collagenⅠ and collagenⅢ, significantly lower mRNA and protein expression of TIMP-1 and Galectin-3, and significantly higher mRNA and protein expression of MMP-2, and the most obvious changes were in the 9th weeks of modeling [collagenⅠ mRNA (2 -ΔΔCt): 4.70±1.19 vs. 10.21±1.62, collagenⅢ mRNA (2 -ΔΔCt): 3.03±0.46 vs. 13.84±1.93, TIMP-1 mRNA (2 -ΔΔCt): 1.90±0.19 vs. 4.55±0.43, TIMP-1/GAPDH: 0.33±0.04 vs. 0.67±0.05, Galectin-3 (ng/L): 489.93±79.30 vs. 821.72±94.09, MMP-2 mRNA (2 -ΔΔCt): 0.37±0.07 vs. 0.03±0.01, MMP-2/GAPDH: 0.69±0.09 vs. 0.21±0.04, all P < 0.05]. Masson staining showed that myocardial tissue fibrosis was obvious in the heart failure group, and the degree of fibrosis in the tanshinoneⅡA group was reduced. ② In vitro, compared with the blank control group, the proliferation rate, collagenⅠ, collagen Ⅲ and TIMP-1 expression and Galectin-3 content of myocardial fibroblasts were significantly increased, and MMP-2 expression was significantly decreased in the angiotensin group at 24 h and 48 h of culture. Compared with the angiotensin group, the proliferation rate of cardiac fibroblasts and the expression of collagenⅠ, collagen Ⅲ and TIMP-1 and the content of Galectin-3 were significantly decreased, and the expression of MMP-2 mRNA was significantly increased in the angiotensin + tanshinone ⅡA group, and the most significant changes were at 48 hours of culture [proliferation rate: (57.0±3.7)% vs. (67.0±2.4)%, collagenⅠmRNA (2 -ΔΔCt): 551.43±67.10 vs. 871.48±12.25, collagenⅢ mRNA (2 -ΔΔCt): 233.76±18.73 vs. 385.51±31.35, TIMP-1 mRNA (2 -ΔΔCt): 238.69±17.37 vs. 351.84±26.17, Galectin-3 (ng/L): 283.76±28.73 vs. 415.51±31.35, MMP-2 mRNA (2 -ΔΔCt): 108.54±12.10 vs. 51.47±6.25, all P < 0.05]. Conclusion:Tanshinone ⅡA can improve cardiac function, inhibit myocardial fibrosis and improve myocardial remodeling in rats with I/R-induced heart failure.

Diagnostic prediction formula for diabetic nephropathy based on serum TFF3, SFRP5, Gal-3 and NES-1 / 国际生物医学工程杂志

Objective:To investigate the expression and correlation of serum trefoil factor 3 (TFF3), serum secreted frizzled-related protein 5 (SFRP5), galectin-3 (Gal-3), and nesfatin-1 (NES-1) in patients with type 2 diabetes(T2DM), diabetic nephropathy(DN), chronic kidney disease (CKD), and healthy controls. To explore the relationship between the above factors and the diagnosis of DN and to establish a diagnostic formula for the diagnosis of DN combined with the above four factors.Methods:In each group 36 patients hospitalized in Tianjin Third Central Hospital from April 2017 to June 2019 were enrolled. 36 healthy volunteers were also chosen as the healthy control group. After 8 to 10 hours of fasting, the venous blood of the subjects in each group was centrifuged, the serum was collected for detection, the serum levels of TFF3, SFRP5, Gal-3, and NES-1 were compared, and the Pearson correlation analysis was performed. According to whether the diagnosis of DN was repeated, the subjects were divided into the DN group and the non-DN group (including a healthy control group, T2DM group, and CKD group). The four datasets were analyzed by binary logistic regression, and the diagnostic prediction model of DN was established, which was further verified by receiver operating characteristic (ROC).Results:The serum levels of TFF3, Gal-3 and NES-1 in DN groups were significantly higher than those in healthy control group, T2DM group and CKD group (all P<0.05), but the serum level of SFRP5 in DN group was significantly lower than that in healthy control group, T2DM group and CKD group (all P<0.05). The differences between the four groups in the four aforementioned indicators were all statistically significant (all P<0.001). The Pearson correlation analysis showed that there was a significant correlation between the above four indicators (all P<0.01). The area under the ROC curve of TFF3, SFRP5, Gal-3, and NES-1 was 0.849, 0.807, 0.882, and 0.841 respectively. The area under the curve diagnosed by the combination of four indicators (0.986) was significantly higher than that of a single indicator, and the difference was statistically significant ( Z=3.75, 4.08, 3.63, 4.06, all P<0.05). Conclusions:The joint prediction model based on serum TFF3, SFRP5, Gal-3, and NES-1 can effectively improve the diagnostic accuracy of DN and provide an important basis for clinical diagnosis of DN.

Expression and Significance of Galectin⁃3 in Colon Tissue and Serum in Ulcerative Colitis / 胃肠病学

Galectin⁃3 is an endogenous lectin with extensive immunomodulatory effects, and plays an important role in inflammatory response, autoimmunity and tumorigenesis. However, the expression of galectin⁃3 in ulcerative colitis (UC) and its relationship with disease activity of UC are unclear. Aims: To detect the expression of galectin⁃3 in colon tissue and serum in UC patients, and explore the relationship between galectin⁃3 and disease activity. Methods: Thirty⁃ three patients with UC diagnosed and treated from March 2019 to December 2019 at the Second Affiliated Hospital of Zhengzhou University were recruited, and 20 paracancerous normal tissue of colon cancer patients were served as controls. The expression of galectin ⁃ 3 in colon tissue was detected by immunohistochemistry SABC. Serum samples of 24 UC patients and 20 healthy controls were collected. Serum level of galectin⁃3 was detected by ELISA. Results: The positive expression rate of galectin⁃3 in colon tissue in UC patients was significantly lower than that in paracancerous normal tissue, and the difference was statistically significant (P<0.05). The positive expression rate in mild UC patients was higher than that in moderate to severe UC patients, and the difference was statistically significant (P<0.05). The positive expression rate in remission stage was higher than that in active stage, and the difference was statistically significant (P<0.05). Serum galectin⁃3 level in UC patients was higher than that in healthy control group, and the difference was statistically significant (P<0.05). Serum galectin ⁃ 3 level in moderate to severe UC patients was higher than that in mild UC group, and the difference was statistically significant (P<0.05). Serum galectin ⁃ 3 level in active UC patients was higher than that in remission UC patients, and the difference was statistically significant (P<0.05). Conclusions: In UC patients, the expression of galectin⁃3 in colon tissue and serum are dysregulated, and the expression of galectin⁃3 in colon tissue is decreased, especially in moderate to severe UC, while the serum galectin⁃3 level is opposite to the tissue expression.

Galectin-3 and fibrosis intensity in Chronic Chagas Cardiomyopathy: a systematic review

ABSTRACT Chronic Chagas Cardiomyopathy (CCC) is the most prevalent type of myocarditis and the main clinical form of the Chagas disease, which has peculiarities such as focal inflammation, structural derangement, hypertrophy, dilation, and intense reparative fibrosis. Many cellular compounds contribute to CCC development. Galectin-3 is a partaker in inflammation and contributes to myocardial fibrosis formation. Some studies showed the connection between Galectin-3 and fibrosis in Chagas disease but are still inconclusive on the guidance for the early implementation of pharmacological therapy. This systematic review evaluated Galectin-3 as a biomarker for fibrosis intensity in CCC. Two independent reviewers have searched five databases (PubMed, EMBASE, Cochrane Library, Scopus, and Lilacs), using the following search terms: galectin-3, biomarkers, fibrosis, Chagas cardiomyopathy, and Chagas disease. Overall, seven studies met the inclusion criteria and made up this review. There were four trials conducted through animal model experiments and three trials with humans. Experimental data in mice indicate an association between Galectin-3 expression and fibrosis in CCC (75% of studies). Data from human studies showed no direct connection between myocardial fibrosis and Galectin-3 expression (80% of studies). Thus, human findings do not provide significant evidence indicating that Galectin-3 is related to fibrosis formation in Chagas disease. Based on the analyzed studies, it is suggested that Galectin-3 might not be a good fibrosis marker in CCC.

Application of ultrasound quantitative technique combined with serum microRNA-599 and galectin-3 in cervical lymph node metastasis of papillary thyroid carcinoma / 中国医师进修杂志

Objective:To investigate the application of ultrasound thyroid imaging report and data system (TI-RADS) score, serum galectin-3, microRNA (miR) -599 in cervical lymph node metastasis of papillary thyroid carcinoma (PTC).Methods:A total of 98 patients with PTC admitted to China Resources Medical Huaibei Miners General Hospital from March 2019 to March 2021 were selected and divided into the metastasis group (48 cases) and the non-metastasis group (50 cases) according to the state of cervical lymph node metastasis dignosedby the pathological examination. The baseline data, ultrasound TI-RADS score, serum galectin-3, miR-599 were compared between the two groups. Multivariate Logistic regression analysis was used to analyze the related factors of cervical lymph node metastasis, receiver operating characteristic (ROC) curve and the area under curve (AUC) were used to analyze the value ofpredicting cervical lymph node metastasis.Results:The ultrasound TI-RADS scores and galectin-3 level in the metastasis group were higher than those in the non-metastasis group: (11.72 ± 2.85) scores vs. (8.15 ± 2.60) scores, (5.54 ± 1.76) μg/L vs. (4.02 ± 1.27) μg/L, the miR-599 level in the metastasis group was lower than that in the non-metastasis group: 0.25 ± 0.08 vs. 0.36 ± 0.10, there were statistical differences ( P<0.05). The results of multivariate Logistic regression analysis showed that the ultrasound TI-RADS score, serum galectin-3 and miR-599 were still associated with cervical lymph node metastasis in PTC patients after controlling the clinical stage ( P<0.05). The results of ROC curve analysis showed that the AUC for ultrasound TI-RADS score, serum galectin-3 combined with miR-599 in evaluating cervical lymph node metastasis was the largest (0.889). The metastasis rate of patients with high levels of ultrasound TI-RADS and serum galectin-3 were higher than those with low levels, and the metastasis rate of patients with high level of miR-599 was lower than that of patients with low level , there were statistical differences ( P<0.05). Conclusions:Ultrasound TI-RADS score, serumgalectin-3, miR-599 are related to cervical lymph node metastasis in PTC patients, and combined detection is expected to become a scheme for evaluating cervical lymph node metastasis.