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.

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.

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.

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.

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.

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.

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.

Preditores de Mortalidade Total e Eventos Arrítmicos Graves em Pacientes com Insuficiência Cardíaca Não Isquêmica: O Papel da Galectina-3 / Predictors of Total Mortality and Serious Arrhythmic Events in Non-Ischemic Heart Failure Patients: The Role of Galectin-3

Resumo Fundamento: A estratificação de risco continua sendo clinicamente desafiadora em pacientes com insuficiência cardíaca (IC) de etiologia não isquêmica. A galectina-3 é um marcador sérico de fibrose que pode ajudar no prognóstico. Objetivo: Determinar o papel da galectina-3 como preditora de eventos arrítmicos graves e mortalidade total. Métodos: Este é um estudo de coorte prospectivo que incluiu 148 pacientes com IC não isquêmica. Todos os pacientes foram submetidos a uma avaliação clínica e laboratorial abrangente para coleta de dados de referência, incluindo níveis de galectina-3 sérica. O desfecho primário foi a ocorrência de síncope arrítmica, intervenções apropriadas do cardioversor desfibrilador implantável, taquicardia ventricular sustentada ou morte súbita cardíaca. O desfecho secundário foi a morte por todas as causas. Para todos os testes estatísticos, considerou-se significativo o valor p<0,05 (bicaudal). Resultados: Em seguimento mediano de 941 dias, os desfechos primário e secundário ocorreram em 26 (17,5%) e 30 (20%) pacientes, respectivamente. A galectina-3 sérica>22,5 ng/mL (quartil mais alto) não foi preditora de eventos arrítmicos graves (HR: 1,98; p=0,152). Os preditores independentes do desfecho primário foram diâmetro diastólico final do ventrículo esquerdo (DDFVE)>73 mm (HR: 3,70; p=0,001), ventilação periódica durante o exercício (VPE) no teste de esforço cardiopulmonar (HR: 2,67; p=0,01) e taquicardia ventricular não sustentada (TVNS)>8 batimentos na monitorização por Holter (HR: 3,47; p=0,027). Os preditores de morte por todas as causas foram: galectina-3>22,5 ng/mL (HR: 3,69; p=0,001), DDFVE>73 mm (HR: 3,35; p=0,003), VPE (HR: 3,06; p=0,006) e TVNS>8 batimentos (HR: 3,95; p=0,007). A ausência de todos os preditores de risco foi associada a um valor preditivo negativo de 91,1% para o desfecho primário e 96,6% para a mortalidade total. Conclusões: Em pacientes com IC não isquêmica, níveis elevados de galectina-3 não foram preditores de eventos arrítmicos graves, mas foram associados à mortalidade total. A ausência de preditores de risco revelou um subgrupo prevalente de pacientes com IC com excelente prognóstico.

Abstract Background: Risk stratification remains clinically challenging in patients with heart failure (HF) of non-ischemic etiology. Galectin-3 is a serum marker of fibrosis that might help in prognostication. Objective: To determine the role of galectin-3 as a predictor of major arrhythmic events and overall mortality. Methods: We conducted a prospective cohort study that enrolled 148 non-ischemic HF patients. All patients underwent a comprehensive baseline clinical and laboratory assessment, including levels of serum galectin-3. The primary outcome was the occurrence of arrhythmic syncope, appropriate implantable cardioverter defibrillator therapy, sustained ventricular tachycardia, or sudden cardiac death. The secondary outcome was all-cause death. For all statistical tests, a two-tailed p-value<0.05 was considered significant. Results: In a median follow-up of 941 days, the primary and secondary outcomes occurred in 26 (17.5%) and 30 (20%) patients, respectively. Serum galectin-3>22.5 ng/mL (highest quartile) did not predict serious arrhythmic events (HR: 1.98, p=0.152). Independent predictors of the primary outcome were left ventricular end-diastolic diameter (LVEDD)>73mm (HR: 3.70, p=0.001), exercise periodic breathing (EPB) on cardiopulmonary exercise testing (HR: 2.67, p=0.01), and non-sustained ventricular tachycardia (NSVT)>8 beats on Holter monitoring (HR: 3.47, p=0.027). Predictors of all-cause death were galectin-3>22.5 ng/mL (HR: 3.69, p=0.001), LVEDD>73mm (HR: 3.35, p=0.003), EPB (HR: 3.06, p=0.006), and NSVT>8 beats (HR: 3.95, p=0.007). The absence of all risk predictors was associated with a 91.1% negative predictive value for the primary outcome and 96.6% for total mortality. Conclusions: In non-ischemic HF patients, elevated galectin-3 levels did not predict major arrhythmic events but were associated with total mortality. Absence of risk predictors revealed a prevalent subgroup of HF patients with an excellent prognosis.

Galectina-3 Associada a Formas Graves e Mortalidade em Longo Prazo em Pacientes com Doença de Chagas / Galectin-3 Associated with Severe Forms and Long-term Mortality in Patients with Chagas Disease

Resumo Fundamento As características histopatológicas da doença de Chagas (DCC) são: presença de miocardite, destruição das fibras cardíacas e fibrose miocárdica. A Galectina-3 (Gal-3) é um biomarcador envolvido no mecanismo de fibrose e inflamação que pode ser útil para a estratificação de indivíduos com DCC por risco. Objetivos Nosso objetivo foi avaliar se níveis elevados de Gal-3 estão associados a formas graves de cardiomiopatia chagásica (CC) e são preditivos de mortalidade. Métodos Estudamos doadores de sangue (DS) positivos para anti-T. cruzi: não-CC-DS (187 DS sem CC com eletrocardiograma [ECG] e fração de ejeção do ventrículo esquerdo [FEVE] normais); CC-Não-Dis-DS (46 DS com CC e apresentando ECG anormal, mas FEVE normal); e 153 controles negativos correspondentes. Esta amostra foi composta por 97 pacientes com CC grave (CC-Dis). Usamos as correlações de Kruskall-Wallis e Spearman para testar a hipótese de associações, assumindo um p bicaudal <0,05 como significativo. Resultados O nível de Gal-3 foi de 12,3 ng/mL para não-CC-DS, 12,0 ng/mL para CC-Não-Dis-DS, 13,8 ng/mL para controles e 15,4 ng/mL para CC-Dis. FEVE <50 foi associada a níveis mais elevados de Gal-3 (p=0,0001). Em nosso modelo de regressão linear ajustado, encontramos associação entre os níveis de Gal-3 e os parâmetros do ecocardiograma em indivíduos positivos para T. cruzi. Nos pacientes CC-Dis, encontramos uma associação significativa de níveis mais elevados de Gal-3 (≥15,3 ng/mL) e morte ou transplante cardíaco em acompanhamento de cinco anos (Hazard ratio - HR 3,11; IC95% 1,21- 8,04; p=0,019). Conclusões Em pacientes com CC, níveis mais elevados de Gal-3 estiveram significativamente associados a formas graves da doença e maior taxa de mortalidade em longo prazo, o que significa que pode ser um meio efetivo para identificar pacientes de alto risco. (Arq Bras Cardiol. 2021; 116(2):248-256)

Abstract Background The histopathological characteristics of Chagas disease (ChD) are: presence of myocarditis, destruction of heart fibers, and myocardial fibrosis. Galectin-3 (Gal-3) is a biomarker involved in the mechanism of fibrosis and inflammation that may be useful for risk stratification of individuals with ChD. Objectives We sought to evaluate whether high Gal-3 levels are associated with severe forms of Chagas cardiomyopathy (CC) and whether they are predictive of mortality. Methods We studied anti-T. cruzi positive blood donors (BD): Non-CC-BD (187 BD without CC with normal electrocardiogram [ECG] and left ventricular ejection fraction [LVEF]); CC-Non-Dys-BD (46 BD with CC with abnormal ECG but normal LVEF); and 153 matched serum-negative controls. This cohort was composed of 97 patients with severe CC (CC-Dys). We used Kruskall-Wallis and Spearman's correlation to test hypothesis of associations, assuming a two-tailed p<0.05 as significant. Results The Gal-3 level was 12.3 ng/mL for Non-CC-BD, 12.0 ng/mL for CC-Non-Dys-BD, 13.8 ng/mL for controls, and 15.4 ng/mL for CC-Dys. LVEF<50 was associated with higher Gal-3 levels (p=0.0001). In our linear regression adjusted model, we found association between Gal-3 levels and echocardiogram parameters in T. cruzi-seropositive subjects. In CC-Dys patients, we found a significant association of higher Gal-3 levels (≥15.3 ng/mL) and subsequent death or heart transplantation in a 5-year follow-up (Hazard ratio - HR 3.11; 95%CI 1.21-8.04; p=0.019). Conclusions In ChD patients, higher Gal-3 levels were significantly associated with severe forms of the disease and more long-term mortality, which means it may be a useful means to identify high-risk patients. (Arq Bras Cardiol. 2021; 116(2):248-256)

Evaluation of galectin-3 levels in patients with type 2 diabetes mellitus and chronic kidney disease / Avaliação dos níveis de galectina-3 em pacientes com diabetes mellitus tipo 2 e doença renal crônica

ABSTRACT INTRODUCTION: Type 2 diabetes mellitus (T2DM) is the most common manifestation of diabetes, accounting for about 90% of diagnosed cases. The causes of T2DM are not fully understood, but its pathogenesis is possibly associated with increased adiposity and a chronic low-grade inflammatory response. The glycoprotein galectin-3 (Gal-3) is known to play an important role in the modulation of blood glucose, adiposity, and inflammation. OBJECTIVES: The aim of this study was to evaluate Gal-3 levels in patients with T2DM and chronic kidney disease (CKD), in addition to relating them with complications and comorbidities present in these patients, comparing them to a control group. MATERIAL AND METHODS: Gal-3 was evaluated in 84 selected individuals, of which 42 had clinical and laboratory diagnosis of T2DM and CKD (treated at Santa Casa Hospital in Belo Horizonte, Minas Gerais, Brazil), and 42 individuals from the local community, with no history of diabetes (control group). RESULTS AND DISCURSION: Gal-3 levels were significantly higher (p = 0.012) in the T2DM group (15.17 ± 5.54 ng/ml) when compared to the control group (12.62 ± 3.2 ng/ml). There was a tendency for higher levels of Gal-3 in diabetic patients with hypertension (15.74 ± 5.61 ng/ml) when compared to patients without this complication (10.96 ± 2.49 ng/ml) (p = 0.069) CONCLUSION: The results suggest that Gal-3 may be involved in the pathophysiology of T2DM and still be a promising biomarker associated with hypertension in this group.

RESUMEN INTRODUCCIÓN: La diabetes mellitus tipo 2 (DM2) es la forma más común de la diabetes; representa alrededor del 90% de los casos diagnosticados. Todavía no se conocen por completo las causas de la DM2, pero posiblemente su etiopatogénesis se relaciona con el aumento de adiposidad y una respuesta inflamatoria crónica de bajo grado. Se sabe que la glicoproteína galectina 3 (Gal-3) juega un papel importante en la modulación de glucemia, adiposidad e inflamación. OBJETIVOS: Evaluar los niveles de Gal-3 en pacientes con DM2 y enfermedad renal crónica, además de relacionarlos con las otras complicaciones y comorbilidades presentes en eses individuos, comparándolos con un grupo control. MATERIAL Y MÉTODO: La Gal-3 fue evaluada en 84 pacientes elegidos; entre esos, 42 poseían el diagnóstico clínico y de laboratorio de DM2 y enfermedad renal crónica (atendidos en el Hospital Santa Casa de Belo Horizonte, Minas Gerais, Brasil) y 42 eran de la comunidad local, sin historial de diabetes (grupo control). RESULTADOS Y DISCUSIÓN: Los niveles de Gal-3 fueron más altos (p = 0,012) en el grupo con DM2 (15,17 ± 5,54 ng/ml) que en el grupo control (12,62 ± 3,2 ng/ml). Hubo tendencia de mayores niveles de Gal-3 en los pacientes diabéticos con hipertensión (15,74 ± 5,61 ng/ml) que en aquellos sin esa complicación (10,96 ± 2,49 ng/ml) (p = 0,069). CONCLUSIÓN: Los resultados obtenidos apuntan que la Gal-3 puede estar involucrada en la etiología de la DM2 y aún ser un biomarcador prometedor de hipertensión en ese grupo.

RESUMO INTRODUÇÃO: O diabetes mellitus tipo 2 (DM2) é a manifestação mais comum do diabetes; representa cerca de 90% dos casos diagnosticados. As causas do DM2 ainda não foram completamente estabelecidas, mas sua patogênese está, possivelmente, relacionada com o aumento da adiposidade e uma resposta inflamatória crônica de baixo grau. Sabe-se que a glicoproteína galectina-3 (Gal-3) possui papel importante na modulação de glicemia, adiposidade e inflamação. OBJETIVOS: Avaliar os níveis de Gal-3 em pacientes com DM2 e doença renal crônica, além de relacioná-los com as demais complicações e comorbidades presentes nesses indivíduos, comparando-os com um grupo-controle. MATERIAL E MÉTODOS:: A Gal-3 foi avaliada em 84 pacientes selecionados; destes, 42 possuíam o diagnóstico clínico e laboratorial de DM2 e doença renal crônica (atendidos no Hospital Santa Casa de Belo Horizonte, Minas Gerais, Brasil), e 42 eram da comunidade local, sem histórico de diabetes (grupo-controle). RESULTADOS E DISCUSSÃO: Os níveis de Gal-3 foram significativamente mais elevados (p = 0,012) no grupo com DM2 (15,17 ± 5,54 ng/ml) quando comparados com os níveis do grupo-controle (12,62 ± 3,2 ng/ml). Houve tendência em maiores níveis de Gal-3 nos pacientes diabéticos com hipertensão (15,74 ± 5,61 ng/ml) em comparação com os pacientes sem essa complicação (10,96 ± 2,49 ng/ml) (p = 0,069). CONCLUSÃO: Os resultados obtidos sugerem que a Gal-3 pode estar envolvida na fisiopatologia do DM2 e ainda ser um promissor biomarcador associado à hipertensão nesse grupo.

Analysis of the efficacy of torasemide combined with levocarnitine in the treatment of chronic heart failure / 中国临床药理学与治疗学

AIM: To explore the efficacy of torasemide combined with levocarnitine in the treatment of chronic heart failure (CHF). METHODS: From July 2018 to July 2020, 75 patients with CHF were recruited and randomly assigned into the control group (37 cases) and the study group (38 cases) according to the random number table method. The control and study groups were treated with levocarnitine and the combination of levocarnitine and torasemide, respectively. The clinical efficacy of the two groups was evaluated. The ventricular remodeling indexes and 6-minute walk test (6MWT) distance were compared between the two groups before and after treatment. The serum levels of serum galectin-3 (Gal-3), interleukin-33 (IL-33), hypersensitive C-reactive protein (hs-CRP), and the plasma concentrations of N terminal pro B type natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP) were determined. RESULTS: (1) After treatment, the total clinical effective rate of the study group (92.11%) was higher than that of the control group (72.97%) (P<0.05). (2) The diastolic interventricular septal thickness (IVST) and diastolic left ventricular posterior wall thickness (LVPWT) were decreased following the treatment in both groups (P<0.05), whereas the treatment led to the increases of the left ventricular mass index (LVMI) and left ventricular ejection fraction (LVEF) in both groups (P<0.05). Compared with those in the control group, IVST and LVPWT in the study group were lower (P<0.05), and LVMI and LVEF were higher (P<0.05). (3) The levels of serum Gal-3, IL-33 and hs-CRP in the two groups were decreased after treatment (P<0.05); compared with those in the control group, the levels of serum Gal-3, IL-33 and hs-CRP were reduced to a greater extent in the study group (P<0.05). (4) Compared with that before treatment, 6MWT distance in both groups increased after treatment (P<0.05); the improvement in the study group was more significant relative to those in the control group (P<0.05). (5) Compared with before treatment, the expression levels of plasma NT-proBNP and BNP in the two groups were decreased after treatment (P<0.05); the reduction of plasma NT-proBNP and BNP levels in the study group was greater than the control group (P<0.05). CONCLUSION: Torasemide combined with levocarnitine is more effective than levocarnitine monotherapy in the treatment of CHF and can significantly improve ventricular remodeling index and motor function, reduce serum inflammation, and enhance cardiac function with definite curative effect.