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.
Humans ; Cytokines/metabolism* ; Galectins/metabolism* ; Hepatitis A Virus Cellular Receptor 2/metabolism* ; Interleukin-4/metabolism* ; Ligands ; Multiple Myeloma/metabolism* ; RNA, Messenger/metabolism* ; Th1 Cells/metabolism* ; Th2 Cells/metabolism*

BACKGROUND: High on-clopidogrel platelet reactivity could be partially explained by loss-of-function alleles of CYP2C19, the enzyme that converts clopidogrel into its active form. Shexiang Tongxin Dropping Pill (STDP) is a traditional Chinese medicine to treat angina pectoris. STDP has been shown to improve blood flow in patients with slow coronary flow and attenuate atherosclerosis in apolipoprotein E-deficient mice. However, whether STDP can affect platelet function remains unknown. OBJECTIVE: The purpose of this study is to examine the potential effects of STDP on platelet function in patients undergoing percutaneous coronary intervention (PCI) for unstable angina. The interaction between the effects of STDP with polymorphisms of CYP2C19 was also investigated. DESIGN, PARTICIPANTS AND INTERVENTION: This was a single-center, randomized controlled trial in patients undergoing elective PCI for unstable angina. Eligible subjects were randomized to receive STDP (210 mg per day) plus dual antiplatelet therapy (DAPT) with clopidogrel and aspirin or DAPT alone. MAIN OUTCOME MEASURES: The primary outcome was platelet function, reflected by adenosine diphosphate (ADP)-induced platelet aggregation and platelet microparticles (PMPs). The secondary outcomes were major adverse cardiovascular events (MACEs) including recurrent ischemia or myocardial infarction, repeat PCI and cardiac death; blood biomarkers for myocardial injury including creatine kinase-MB isoenzyme (CK-MB) and high-sensitive troponin I (hsTnI); and biomarkers for inflammation including intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1) and galectin-3. RESULTS: A total of 118 subjects (mean age: [66.8 ± 8.9] years; male: 59.8%) were included into analysis: 58 in the control group and 60 in the STDP group. CYP2C19 genotype distribution was comparable between the 2 groups. In comparison to the control group, the STDP group had significantly lower CK-MB (P < 0.05) but similar hsTnI (P > 0.05) at 24 h after PCI, lower ICAM-1, VCAM-1, MCP-1 and galectin-3 at 3 months (all P < 0.05) but not at 7 days after PCI (P > 0.05). At 3 months, the STDP group had lower PMP number ([42.9 ± 37.3] vs. [67.8 ± 53.1] counts/μL in the control group, P = 0.05). Subgroup analysis showed that STDP increased percentage inhibition of ADP-induced platelet aggregation only in slow metabolizers (66.0% ± 20.8% in STDP group vs. 36.0% ± 28.1% in the control group, P < 0.05), but not in intermediate or fast metabolizers. The rate of MACEs during the 3-month follow-up did not differ between the two groups. CONCLUSION: STDP produced antiplatelet, anti-inflammatory and cardioprotective effects. Subgroup analysis indicated that STDP inhibited residual platelet reactivity in slow metabolizers only. TRIAL REGISTRATION This study was registered on www.chictr.org.cn: ChiCTR-IPR-16009785.
Adenosine Diphosphate ; Angina, Unstable/chemically induced* ; Animals ; Biomarkers ; Clopidogrel ; Cytochrome P-450 CYP2C19/genetics* ; Drugs, Chinese Herbal ; Galectin 3 ; Humans ; Intercellular Adhesion Molecule-1 ; Male ; Mice ; Percutaneous Coronary Intervention/adverse effects* ; Platelet Aggregation Inhibitors/adverse effects* ; Vascular Cell Adhesion Molecule-1/genetics*

OBJECTIVE: To investigate the regulatory role of α-1, 6-fucosyltransferase (FUT8) in TGF-β1-induced proliferation, migration and fibrosis of human embryonic lung fibroblasts (MRC-5 cells) and explore the underlying molecular mechanism. METHODS: C57/BL6 mice were randomized into 4 groups for treatment with saline (control group), bleomycin, bleomycin+sh-NC or bleomycin+sh-FUT8, and pulmonary fibrosis was observed using Masson staining.MRC-5 cells were transfected with si-NC, FUT8 siRNA (si-FUT8), or both si-FUT8 and a galectin-3(Gal-3) overexpression plasmid (pcDNA3.1-Gal) prior to TGF-β1 treatment, and the changes in cell proliferation and migration were assessed using CCK-8 assay, BrdU assay, and wound healing assay; the changes in the expression levels of α-SMA, collagen I (COLIA1) and extracellular matrix fibronectin (FN) were detected with real-time quantitative PCR (RT-qPCR) and Western blotting.The interaction of FUT8 and Gal-3 was tested using coimmunoprecipitation (Co-IP) assay, and the effect of FUT8 silencing on Gal-3 and FAK/Akt signaling pathways was analyzed. RESULTS: FUT8 knockdown significantly reduced bleomycin-induced extracellular collagen deposition in the lung tissues of the mice.Silencing FUT8 obviously inhibited cell proliferation (P < 0.05) and migration mediated by TGF-β1.FUT8 knockdown down-regulated the mRNA and protein levels of α-SMA, COLIA1 and FN (P < 0.05) in the cells.Coimmunoprecipitation analysis showed that FUT8 interacted with Gal-3.Silencing FUT8 significantly down-regulated Gal-3 expression and inhibited the activation of the FAK/Akt signaling pathway (P < 0.05).Overexpression of Gal-3 obviously reversed the effects of FUT8 silencing on cell proliferation, migration and fibrosis (P < 0.05). CONCLUSION FUT8 regulates TGF-β1-induced proliferation, migration and fibrosis of MRC-5 cells by modulating Gal-3 expression, in which the FAK/Akt pathway may play a role.
Animals ; Bleomycin/metabolism* ; Fibroblasts/metabolism* ; Fibrosis ; Fucosyltransferases/metabolism* ; Galectin 3/genetics* ; Humans ; Lung/metabolism* ; Mice ; Proto-Oncogene Proteins c-akt/metabolism* ; Transforming Growth Factor beta1/metabolism*

The incidence of hematological malignant tumor is increasing year by year, and seriously affecting the human health. In addition to the traditional radiation and chemotherapy, immunotherapy has achieved a certain effect in the treatment of blood tumor, but it is limited by exhaustion of CD8
CD8-Positive T-Lymphocytes ; Galectins ; Hematologic Neoplasms ; Hepatitis A Virus Cellular Receptor 2 ; Humans ; Immunotherapy

Objective: To evaluate possible effects of Gelctin-9 on acute graft versus host disease (aGVHD) development and clinical outcomes in patients before and afer allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Peripheral blood samples were obtained from 29 patients and 15 healthy volunteers with heparin anticoagulant tubes. Samples were analyzed using ELISA kits to measure the serum concentrations of Galectin-9. Results: Patients developing aGVHD had significantly lower level of Galectin-9 [ (7.96±1.18) μg/L] before allo-HSCT compared with those not developing aGVHD [ (12.37±0.97) μg/L, P<0.001]. And after allo-HSCT, the consentration of Galectin-9 increased markedly in patients developing aGVHD [ (17.78±1.78) μg/L] compared with those not developing aGVHD [ (9.45±0.80) μg/L, P<0.001]. Patients developing 3-4 grade aGVHD had significantly higher level of Galectin-9 [ (23.25±2.59) μg/L] compared with those developing 1-2 grade aGVHD [ (14.37±1.45) μg/L, P=0.008] and those without aGVHD [ (9.45±0.80) μg/L, P<0.001]. The patients with lower level of Galectin-9 after allo-HSCT (<13.61 μg/L) showed more favorable clinical outcomes compared with those with higher level of Galectin-9 (≥13.61 μg/L) . The 3-year overall survival rates were (100.00±6.05) % and (69.23±12.80) %, respectively (P=0.009) . The cumulative incidence of non-relapse mortality was significantly higher in high Galectin-9 group [ (23.08±11.69) %] in comparison with low Gaelctin-9 group [ (0.00±7.39) %] (P=0.023) . There was no significant difference between the two groups in terms of the cumulative incidence of relapse. The cumulative incidence of relapse at 3 years were (8.33±7.98) % and (12.50±8.27) % in high and low Galectin-9 groups, respectively (P=0.708) . Conclusions: The serum concentration of Galectin-9 at the time of engraftment after allo-HSCT may be used as a predictor for the development and severity of aGVHD. Galectin-9 might be considered as a potential new approach to regulate transplant rejection to achieve desirable survival.
Galectins ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Incidence ; Survival Rate ; Transplantation, Homologous

Galectin-4 (Gal-4) is a β-galactoside-binding protein mostly expressed in the gastrointestinal tract of animals. Although intensive functional studies have been done for other galectin isoforms, the immunoregulatory function of Gal-4 still remains ambiguous. Here, we demonstrated that Gal-4 could bind to CD14 on monocytes and induce their differentiation into macrophage-like cells through the MAPK signaling pathway. Gal-4 induced the phenotypic changes on monocytes by altering the expression of various surface molecules, and induced functional changes such as increased cytokine production and matrix metalloproteinase expression and reduced phagocytic capacity. Concomitant with these changes, Gal-4-treated monocytes became adherent and showed elongated morphology with higher expression of macrophage markers. Notably, we found that Gal-4 interacted with CD14 and activated the MAPK signaling cascade. Therefore, these findings suggest that Gal-4 may exert the immunoregulatory functions through the activation and differentiation of monocytes.
Animals ; Antigens, CD14 ; Cell Differentiation ; Galectin 4 ; Galectins ; Gastrointestinal Tract ; Macrophages ; Monocytes ; Protein Isoforms

OBJECTIVE: To study the correlation of galectin-3 level in bronchoalveolar lavage fluid (BALF) with Mycoplasma pneumoniae (MP) load and cellular immunity of neutrophils and macrophages in the airway in children with refractory MP pneumonia (RMPP). METHODS: A total of 64 children with RMPP who were hospitalized from January 2013 to January 2017 were enrolled. In addition to the conservative medical treatment, all the 64 children with RMPP were given bronchoalveolar lavage in the acute stage (5-7 days after admission) and 48 out of the 64 children were given bronchoalveolar lavage in the recovery stage (10-14 days after admission). Four milliliters of BALF of the affected lung lobe or segment were collected. ELISA was used to measure the level of galectin-3 in BALF supernatant. RT-PCR was used to measure MP load. Hematoxylin and eosin staining was used to measure the percentage of neutrophils and macrophages. Six children with bronchial foreign bodies were enrolled as the control group. RESULTS: The RMPP group had a significantly higher level of galectin-3 in BALF in both the acute and recovery stages than the control group (P<0.01), and the level of galectin-3 in the acute stage was significantly higher than in the recovery stage (P<0.01). The RMPP group had a significantly higher percentage of neutrophils in BALF in both the acute and recovery stages than the control group (P<0.01), and the percentage of neutrophils in the acute stage was significantly higher than in the recovery stage (P<0.01). The RMPP group had a significantly lower percentage of macrophages in BALF in both the acute and recovery stages than the control group (P<0.01), but there was no significant difference in the percentage of macrophages between the acute and recovery stages (P>0.05). The RMPP group had a significantly higher MP load in BALF in both the acute and recovery stages than the control group (P<0.01), and the MP load in the acute stage was significantly higher than in the recovery stage (P<0.01). In the children with RMPP, galectin-3 level in BALF in the acute stage was positively correlated with MP load and the percentage of neutrophils (r=0.789 and 0.726 respectively; P<0.01). CONCLUSIONS Galectin-3 is involved in the process of airway inflammation in children with RMPP, and the level of galectin-3 in BALF is positively correlated with MP load. RMPP is a cellular immune inflammatory lesion with the increase of neutrophils and the reduction in macrophages. Galectin-3 is closely associated with neutrophil chemotaxis and luminal infiltration in children with RMPP. MP load gradually decreases with the recovery from RMPP, but it is not completely eliminated by the immune system in the recovery stage. MP infection can increase the consumption of macrophages in children with RMPP.
Bronchoalveolar Lavage Fluid ; Child ; Galectin 3 ; Humans ; Immunity, Cellular ; Mycoplasma pneumoniae ; Pneumonia, Mycoplasma

BACKGROUND: The early identification of heart failure (HF) risk may favorably affect outcomes, and the combination of multiple biomarkers may provide a more comprehensive and valuable means for improving the risk of stratification. This study was conducted to assess the importance of individual cardiac biomarkers creatine kinase MB isoenzyme (CK-MB), B-type natriuretic peptide (BNP), galectin-3 (Gal-3) and soluble suppression of tumorigenicity-2 (sST2) for HF diagnosis, and the predictive performance of the combination of these four biomarkers was analyzed using random forest algorithms. METHODS: A total of 193 participants (80 patients with HF and 113 age- and gender-matched healthy controls) were included from June 2017 to December 2017. The correlation and regression analysis were conducted between cardiac biomarkers and echocardiographic parameters. The accuracy and importance of these predictor variables were assessed using random forest algorithms. RESULTS: Patients with HF exhibited significantly higher levels of CK-MB, BNP, Gal-3, and sST2. BNP exhibited a good independent predictive capacity for HF (AUC 0.956). However, CK-MB, sST2, and Gal-3 exhibited a modest diagnostic performance for HF, with an AUC of 0.709, 0.711, and 0.777, respectively. BNP was the most important variable, with a remarkably higher mean decrease accuracy and Gini. Furthermore, there was a general increase in predictive performance using the multi-marker model, and the sensitivity, specificity was 91.5% and 96.7%, respectively. CONCLUSION The random forest algorithm provides a robust method to assess the accuracy and importance of predictor variables. The combination of CK-MB, BNP, Gal-3, and sST2 achieves improvement in prediction accuracy for HF.
Adult ; Algorithms ; Biomarkers ; blood ; metabolism ; Creatine Kinase, MB Form ; blood ; metabolism ; Echocardiography ; Female ; Galectin 3 ; blood ; metabolism ; Heart Failure ; blood ; metabolism ; pathology ; Humans ; Male ; Middle Aged ; Natriuretic Peptide, Brain ; blood ; metabolism

PURPOSE: Chironomids (nonbiting midges) are widely and abundantly distributed near ponds, rivers, and artificially dammed pools used for irrigation. Chironomids contain allergens and cause airway allergy in humans. In this study, we aimed to examine the allergic potential of chironomids in inhabitants living near artificially dammed pools. METHODS: We examined immunoglobulin E (IgE) reactivity to chironomid extracts in the sera of residents living around installed dams and assessed the correlations of IgE responses between chironomids (Chironomus flaviplumus, Chironomus kiiensis, Cricotopus bicinctus) and house dust mites (Dermatophagoides farinae). In addition, we identified potential IgE binding proteins specific for adult C. bicinctus, a popular species in Korea. Specific IgE antibodies in sera collected from the participants against the extracts were tested using enzyme-linked immunosorbent assay (ELISA). RESULTS: The average IgE-positive rates were 10.4%, 8.1%, and 8.2% in C. bicinctus, C. flaviplumus, and C. kiiensis, respectively. The IgE-positive rate and IgE titer of C. bicinctus antigen were higher in residents living around installed dams than in those who lived other places (P = 0.013). Western blotting using sera having high IgE titers to C. bicinctus in ELISA showed the presence of a protein of approximately 42 kDa that was homologous to the actin protein isoform in C. bicinctus extracts as demonstrated using mass spectrometry. CONCLUSIONS: Our results showed that people living near installed dams were more sensitized to C. bicinctus and that the 42 kDa IgE-binding protein could be useful for further studies on chironomid allergic disease and clinical applications.
Actins ; Adult ; Allergens ; Antibodies ; Blotting, Western ; Chironomidae ; Enzyme-Linked Immunosorbent Assay ; Galectin 3 ; Humans ; Hypersensitivity ; Immunoglobulin E ; Immunoglobulins ; Korea ; Mass Spectrometry ; Ponds ; Pyroglyphidae ; Rivers

BACKGROUND: In this study, we investigate the expression of markers of angiogenesis and microvessel density (MVD) in cases of microcystic, elongated and fragmented (MELF) pattern, with its prognostic role in the survival of endometrioid endometrial adenocarcinomas (EA) patients. METHODS: In this study, 100 cases of EA, 49 cases with MELF pattern and 51 without, were immunohistochemically stained for galectin-1, vascular endothelial growth factor (VEGF), and MVD. Morphometry and statistical (univariate and multivariate) analyses were performed to assess overall survival (OS) and disease-free survival. RESULTS: The expression of VEGF (p<.001) and galectin-1 (p<.001), as well as MVD area (p<.001) and number of vessels/mm² (p<.050), were significantly higher in the +MELF pattern group compared to the –MELF group. A low negative correlation between MELF-pattern and the number of days of survival (p<.001, r=–0.47) was also found. A low positive correlation of MELF-pattern with galectin-1 expression (p<.001, r=0.39), area of vessels/mm² (p<.001, r=0.36), outcome of EA (p<.001, r=0.42) and VEGF expression (p<.001, r=0.39) suggests potential pathological relevance of these factors in the prognosis of EA. A univariate survival analysis indicated a role for all parameters of survival. Multivariate Cox proportional hazard regression analysis revealed that only area of vessels/mm² (hazard ratio [HR], 1.018; 95% confidence interval [CI], 1.002 to 1.033), galectin-1 (HR, 1.049; 95% CI, 1.025 to 1.074) and VEGF (HR, 1.049; 95% CI, 1.022 to 1.077) play key roles in OS. CONCLUSIONS: This study reports an increase in MVD, VEGF and galectin-1 expression in EA with MELF pattern and suggests that MELF pattern, along with the angiogenic profile, may be a prognostic factor in EA.
Adenocarcinoma ; Disease-Free Survival ; Galectin 1 ; Humans ; Microvessels ; Prognosis ; Vascular Endothelial Growth Factor A