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*

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

BACKGROUND: Mesenchymal stromal cells (MSCs) are multipotent stem cells that can differentiate into several cell types. In addition, many studies have shown that MSCs modulate the immune response. However, little information is currently available regarding the maintenance of immunomodulatory characteristics of MSCs through passages. Therefore, we investigated and compared cytokine and gene expression levels from adipose (AD) and bone marrow (BM)-derived MSCs relevant to immune modulation from early to late passages. METHODS: MSC immunophenotype, growth characteristics, cytokine expressions, and gene expressions were analyzed. RESULTS: AD-MSCs and BM-MSCs had similar cell morphologies and surface marker expressions from passage 4 to passage 10. Cytokines secreted by AD-MSCs and BM-MSCs were similar from early to late passages. AD-MSCs and BM-MSCs showed similar immunomodulatory properties in terms of cytokine secretion levels. However, the gene expressions of tumor necrosis factor-stimulated gene (TSG)-6 and human leukocyte antigen (HLA)-G were decreased and gene expressions of galectin-1 and -3 were increased in both AD- and BM-MSCs with repeated passages. CONCLUSION: Our study showed that the immunophenotype and expression of immunomodulation-related cytokines of AD-MSCs and BM-MSCs immunomodulation through the passages were not significantly different, even though the gene expressions of both MSCs were different.
Bone Marrow ; Cytokines* ; Galectin 1 ; Gene Expression ; Humans* ; Immunomodulation ; Leukocytes ; Mesenchymal Stromal Cells* ; Multipotent Stem Cells ; Necrosis

BACKGROUND: The decidua has been implicated in the “terminal pathway” of human term parturition, which is characterized by the activation of pro-inflammatory pathways in gestational tissues. However, the transcriptomic changes in the decidua leading to terminal pathway activation have not been systematically explored. This study aimed to compare the decidual expression of developmental signaling and inflammation-related genes before and after spontaneous term labor in order to reveal their involvement in this process. METHODS: Chorioamniotic membranes were obtained from normal pregnant women who delivered at term with spontaneous labor (TIL, n = 14) or without labor (TNL, n = 15). Decidual cells were isolated from snap-frozen chorioamniotic membranes with laser microdissection. The expression of 46 genes involved in decidual development, sex steroid and prostaglandin signaling, as well as pro- and anti-inflammatory pathways, was analyzed using high-throughput quantitative real-time polymerase chain reaction (qRT-PCR). Chorioamniotic membrane sections were immunostained and then semi-quantified for five proteins, and immunoassays for three chemokines were performed on maternal plasma samples. RESULTS: The genes with the highest expression in the decidua at term gestation included insulin-like growth factor-binding protein 1 (IGFBP1), galectin-1 (LGALS1), and progestogen-associated endometrial protein (PAEP); the expression of estrogen receptor 1 (ESR1), homeobox A11 (HOXA11), interleukin 1β (IL1B), IL8, progesterone receptor membrane component 2 (PGRMC2), and prostaglandin E synthase (PTGES) was higher in TIL than in TNL cases; the expression of chemokine C-C motif ligand 2 (CCL2), CCL5, LGALS1, LGALS3, and PAEP was lower in TIL than in TNL cases; immunostaining confirmed qRT-PCR data for IL-8, CCL2, galectin-1, galectin-3, and PAEP; and no correlations between the decidual gene expression and the maternal plasma protein concentrations of CCL2, CCL5, and IL-8 were found. CONCLUSIONS: Our data suggests that with the initiation of parturition, the decidual expression of anti-inflammatory mediators decreases, while the expression of pro-inflammatory mediators and steroid receptors increases. This shift may affect downstream signaling pathways that can lead to parturition.
Chemokines ; Cytokines ; Decidua ; Estrogen Receptor alpha ; Estrogens ; Female ; Galectin 1 ; Galectin 3 ; Galectins ; Gene Expression* ; Genes, Homeobox ; Humans ; Immunoassay ; Interleukin-8 ; Interleukins ; Leukocytes ; Membranes ; Microdissection ; Parturition* ; Plasma ; Pregnancy ; Pregnant Women ; Progesterone ; Real-Time Polymerase Chain Reaction ; Receptors, Progesterone ; Receptors, Steroid ; Sexual Development ; Transcriptome*

BACKGROUNDPelvic organ prolapse (POP) is a major health problem in adult women that involves many factors. No proteomic analysis has been conducted exclusively in POP patients. This study aimed to identify the differential expression of proteins that may be involved in POP by proteomic analysis.

METHODSSamples of the uterosacral ligament (USL) were collected from five POP patients and five non-POP patients matched according to age, parity, and menopausal status and analyzed using two-dimensional electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the mRNA expression of proteins that showed differential expression in the proteomic analyses.

RESULTSProteins differentially expressed between POP and non-POP patients were detected. Eight proteins that were down-regulated in the POP group were identified by MALDI-TOF-MS. These proteins included electron transfer flavoprotein, apolipoprotein A-I, actin, transgelin, cofilin-1, cyclophilin A, myosin, and galectin-1, and their expression was verified by qRT-PCR.

CONCLUSIONUsing comparative proteomics, we identified eight differentially expressed proteins (including four cytoskeleton proteins and three proteins related to apoptosis) in the USL that may be involved in apoptosis associated with the tissue effects in POP pathophysiology.

Actins ; metabolism ; Aged ; Apolipoprotein A-I ; metabolism ; Cyclophilin A ; metabolism ; Cytoskeleton ; metabolism ; Female ; Flavoproteins ; metabolism ; Galectin 1 ; metabolism ; Humans ; Ligaments ; metabolism ; Microfilament Proteins ; metabolism ; Middle Aged ; Muscle Proteins ; metabolism ; Myosins ; metabolism ; Pelvic Organ Prolapse ; metabolism ; Postmenopause ; metabolism ; Proteomics ; methods ; Reverse Transcriptase Polymerase Chain Reaction ; Sacrum ; metabolism ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Uterus ; metabolism

OBJECTIVETo study the expression and prognostic significance of galectin-1 and galectin-3 in different melanocytic lesions.

METHODSThe expression of galectin-1 and galectin-3 in 39 cases of benign nevus, 58 cases of primary cutaneous melanoma, 24 cases of primary mucosal melanoma, 69 cases of melanoma with lymph node metastasis and 8 cases of melanoma with distant metastasis were studied by immunohistochemistry and tissue microarray.

RESULTSThe expression of galectin-1 and galectin-3 was higher in benign nevi than in melanomas (P < 0.01). The nuclear expression of galectin-3 was higher in primary cutaneous melanomas than in primary mucosal melanomas or melanomas with metastases (P < 0.01, respectively). The expression correlated with age of patients (P < 0.05), necrosis (P < 0.05) and survival time (P < 0.01). Clark's level also correlated with survival time in patients with cutaneous melanomas (P = 0.037). TNM staging was the only independent prognostic factor for melanomas (P < 0.01).

CONCLUSIONSThe expression of galectin-1 and galectin-3 is decreased in melanomas. The decrease in nuclear expression of galectin-3 may represent a poor prognostic factor for melanomas. TNM staging is an independent prognostic factor which influences the survival time.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Female ; Galectin 1 ; metabolism ; Galectin 3 ; metabolism ; Humans ; Immunohistochemistry ; Liver Neoplasms ; secondary ; Lung Neoplasms ; secondary ; Lymphatic Metastasis ; Male ; Melanoma ; metabolism ; pathology ; secondary ; Middle Aged ; Nasal Mucosa ; metabolism ; Neoplasm Staging ; Nevus ; metabolism ; pathology ; Skin Neoplasms ; metabolism ; pathology ; Survival Rate ; Young Adult

BACKGROUND AND OBJECTIVES: Existing data on the spatiotemporal expression patterns of a variety of galectins in murine atherosclerosis are limited. We investigated the expression levels of galectins, and their in vivo spatiotemporal expression patterns and statin responsiveness in the inflamed atherosclerotic plaques of apolipoprotein E (apoE)-/- mice. MATERIALS AND METHODS: Galectins expression patterns in aortic atherosclerotic plaques and serum galectin-3 levels were investigated in 26-week-old apoE-/- (n=6) and C57BL/6 mice (n=9). To investigate the spatial and temporal patterns of galectin-1 and galectin-3 in plaques, high-cholesterol diet-fed 26-week-old (n=12) and 36-week-old apoE-/- mice (n=6) were sacrificed and their aortas were examined for galectins' expression using immunoblot analysis and immunohistochemical stain. 36-week-old apoE-/- mice were treated with atorvastatin (n=3, 0.57 mg/kg/day) for the evaluation of its effect on aortic galectins' expression. RESULTS: Immunoblot analyses showed that galectin-1 and galectin-3 were the predominant galectins expressed in murine atherosclerosis. The serum galectin-3 level was significantly higher in apoE-/- mice (p<0.001). While galectin-1 was weakly expressed in both intimal plaques and the media of atherosclerotic aortas, galectin-3 was heavily and exclusively accumulated in intimal plaques. Galectin-3 distribution was colocalized with plaque macrophages' distribution (r=0.66). As the degree of plaque extent and inflammation increased, the intraplaque galectin-3 expression levels proportionally elevated (p<0.01 vs. baseline), whereas galectin-1 expression had not elevated (p=0.14 vs. baseline). Atorvastatin treatment markedly reduced intraplaque galectin-3 and macrophage signals (p<0.001 vs. baseline), whereas it failed to reduce galectin-1 expression in the aortas. CONCLUSION: Galectin-3 is the predominant gal and is colocalized with macrophages within atherosclerotic plaques. Intraplaque galectin-3 expression reflects the degree of plaque inflammation.
Animals ; Aorta ; Apolipoproteins ; Atherosclerosis ; Galectin 1 ; Galectin 3 ; Galectins ; Heptanoic Acids ; Inflammation ; Macrophages ; Mice ; Plaque, Atherosclerotic ; Pyrroles ; Atorvastatin Calcium

OBJECTIVETo study the expression of galectin 3 (Gal-3) and CD82/KAI1 proteins in non-small cell lung cancer (NSCLC) and the correlation between their expression and clinical significance.

METHODSThe expression of Gal-3 and CD82/KAI1 proteins was detected by immunohistochemistry in 160 specimens of NSCLC and 20 specimens of normal lung tissue.

RESULTSThe positive rates of Gal-3 and CD82/KAI1 proteins in the NSCLC were 63.8% and 37.5%, respectively, the positive rates of Gal-3 and CD82/KAI1 proteins in the normal lung tissue were 25.0% and 95.0%, respectively, and there was a significant difference between the two groups (P < 0.01). The expression of Gal-3 and CD82/KAI1 proteins was significantly correlated with the grade of tumor, lymph node metastasis, and pathological-TNM stages (all P < 0.05). Spearman analysis showed that there was a negative correlation between expressions of Gal-3 and CD82/KAI1 in NSCLC (r = -0.732, P < 0.01). Overexpression of Gal-3 and low expression of CD82/KAI1 were related to poor prognosis: the survival rate was significantly lower in the positive Gal-3 group (survival time: 23.0 ± 17.5 months) than that in the negative group (survival time: 71.6 ± 21.6 months) (P < 0.01). The survival rates of the CD82/KAI1-positive group (survival time: 72.5 ± 19.5 months) and CD82/KAI1-negative group (survival time: 21.6 ± 16.1 months) were significantly different (P < 0.01). Multivariate analysis indicated that pTNM stage and positive expression of Gal-3 and CD82/KAI1 are independent prognostic factors of NSCLC (P < 0.01).

CONCLUSIONSThe expression of Gal-3 and CD82/KAI1 may be related to the initiation, development and metastasis of NSCLC. Combined detection of Gal-3 and CD82/KAI1 has an important role in predicting the progression and prognosis of NSCLC.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung ; metabolism ; pathology ; Female ; Galectin 3 ; metabolism ; Humans ; Kangai-1 Protein ; metabolism ; Lung Neoplasms ; metabolism ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Proportional Hazards Models ; Survival Rate

Although mounting evidence indicates the involvement of galectin-3 in cancer progression and metastasis, the underlying molecular mechanisms remain largely unknown. In this study, we investigated the effect and possible mechanism of galectin-3 on the migration and invasion of B16F10, a metastatic melanoma cell line, in which galectin-3 and matrix metalloproteinase-1 (MMP-1) were both found to be highly expressed. Knockdown of galectin-3 with specific siRNA reduced migration and invasion, which was associated with reduced expression of MMP-1. To further investigate the underlying mechanism, we examined the effect of galectin-3 knockdown on the activity of AP-1, a transcriptional factor regulating MMP-1 expression. We found that galectin-3 directly interacted with AP-1 and facilitated the binding of this complex to the MMP-1 promoter that drives MMP-1 transcription. Moreover, silencing of galectin-3 inhibited binding of fra-1 and c-Jun to promoter sites of MMP-1 gene. Consistent with these in vitro findings, our in vivo study demonstrated that galectin-3 shRNA treatment significantly reduced the total number of mouse lung metastatic nodules. Taken together, galectin-3 facilitates cell migration and invasion in melanoma in vitro and can induce metastasis in vivo, in part through, regulating the transcription activity of AP-1 and thereby up-regulating MMP-1 expression.
Animals ; Binding Sites/genetics ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Galectin 3/genetics/*metabolism ; JNK Mitogen-Activated Protein Kinases/metabolism ; Lung Neoplasms/drug therapy/genetics/*secondary ; Matrix Metalloproteinase 1/*genetics/*metabolism ; Melanoma, Experimental/*metabolism/*pathology/secondary ; Mice ; Mice, Inbred C57BL ; NIH 3T3 Cells ; Neoplasm Metastasis ; Promoter Regions, Genetic ; Proto-Oncogene Proteins c-fos/metabolism ; RNA Interference ; RNA, Small Interfering ; Transcription Factor AP-1/*genetics/metabolism ; Transcription, Genetic ; Transcriptional Activation

OBJECTIVES: There is a classical distinction based on clinical criteria between acquired and congenital cholesteatomas. To determine if these two types of lesions show different immunohistochemical features, we have studied the expression patterns of three distinctive galectins (animal lectins implied especially in cellular proliferation and apoptosis) in both types of cholesteatomas and compared it to their expression patterns in external auditory canal skin. METHODS: Our study is based on nine acquired and eight congenital cholesteatomas, obtained from children during ear surgery. Six specimens of normal adult auditory meatal skin served as control. Specimens were analyzed by immunohistochemistry using monoclonal antibodies with galectin-1 and galectin-3, and a polyclonal antibody with galectin-7. RESULTS: We did not observe any differences in the galectin distribution pattern between congenital and acquired pediatric cholesteatomas. Compared to the control group, cholesteatomas present some particular features. There was no expression of galectin-1 and a lower expression of galectin-3 in the epithelium. Furthermore, we observed a preferentially nuclear distribution of galectin-7 in cholesteatomas, whereas it is essentially cytoplasmic in the control group. CONCLUSION: The data reported in this study suggest, on the basis of a lesser marked galectin-3 in cholesteatomas epithelium compared with an external auditory canal skin, that an immature keratinocytes population is at the origin of these lesions and that galectin-3 and galectin-7 play a part in the capacity as apoptosis modulators. Our study does not establish a difference in the galectin expressions of congenital and acquired cholesteatomas, but it constitutes however an additional argument in favor of the "undifferentiated" origin of keratinocytes in cholesteatomas.
Adult ; Antibodies, Monoclonal ; Apoptosis ; Cell Proliferation ; Child ; Cholesteatoma ; Cholesteatoma, Middle Ear ; Cytoplasm ; Ear ; Ear Canal ; Epithelium ; Galectin 1 ; Galectin 3 ; Galectins ; Humans ; Immunohistochemistry ; Keratinocytes ; Lectins ; Skin