Purification and Biochemical Characterization of Novel Galectin from the Black Poplar Medicinal Mushroom Cyclocybe cylindracea (Agaricomycetes) Strain MEST42 from Algeria.

In the present study, a new galectin designated Cyclocybe cylindracea lectin (CCL) was extracted from the fruiting bodies of the wild black popular mushroom C. cylindracea grown in Algeria. The protein was isolated using sepharose 4B as affinity chromatography matrix, and galactose as elutant. The purified galectin was composed of two subunits of 17.873 kDa each, with a total molecular mass of 35.6 kDa. Its agglutinant activity was impeded by galactose and its derivatives, as well as melibiose. Lactose showed the highest affinity, with a minimal inhibitory concentration of 0.0781 mM. CCL was sensitive to extreme pH conditions, and its binding function decreased when incubated with 10 mM EDTA, and it could be restored by metallic cations such as Ca2+, Mg2+, and Zn2+. CCL agglutinated human red blood cells, without any discernible specificity. Circular dichroism spectra demonstrated that its secondary structure contained ß-sheet as dominant fold. In addition, bioinformatics investigation on their peptide fingerprint obtained after MALDI-TOF/TOF ionization using mascot software confirmed that CCL was not like any previous purified lectin from mushroom: instead, it possessed an amino acid composition with high similarity to that of the putative urea carboxylase of Emericella nidulans (strain FGSC A4/ATCC 38163/CBS 112.46/NRRL 194/M139) with 44% of similarity score.

Retrospective Clinical Observation of Correlation between Galectin-3 and Early Herpes Zoster Neuralgia and Post-herpetic Neuralgia.

Background: Herpes Zoster Neuralgia (HZN) and Post-Herpetic Neuralgia (PHN) are neuropathic pain conditions following Varicella Zoster Virus infection. PHN primarily affects individuals aged 60 and above and the pervasive and severe neuropathic pain in PHN leads to significant emotional and psychological distress in approximately 80%-90% of patients, precipitating a decline in their overall quality of life and that of their families. Galectin-3, a pro-inflammatory factor, is implicated in inflammatory responses, potentially influencing neuronal damage and pain signal transmission. Objective: This study aims to evaluate the clinical relevance of serum Galectin-3 in HZN and PHN patients, alongside other contributing factors. Methods: We retrospectively analyzed data collected from 40 HZN patients, 40 non-HZN patients, and 20 healthy controls in our hospital between 2015 and 2017. Variables included demographic data, clinical characteristics, and inflammatory markers. Statistical analyses comprised t-tests, ANOVA, chi-square tests, and multivariate logistic regression. A Receiver Operating Characteristic (ROC) curve was constructed to evaluate Galectin-3's predictive value for PHN. Results: PHN patients showed significantly higher ages, NRS scores, and prevalence of shingles in the head and neck region compared to Non-PHN and Non-HZN groups (P < .05). Elevated levels of IL-6 (66.33±8.93 pg/mL) and Galectin-3 (2.44±0.29 ng/mL) were observed in HZN patients. Galectin-3 emerged as a significant risk factor for PHN development (P < .05), while other factors such as age, shingles location, IL-6, and T lymphocyte subsets did not show a significant impact. Conclusion: Galectin-3 may serve as a predictive biomarker for PHN development, offering insights into its pathophysiology and potential therapeutic targets. Patients with elevated Galectin-3 levels might benefit from specific targeted therapies or interventions aimed at reducing Galectin-3 levels and mitigating its effects.

The regulation of tolerogenic dendritic cells by a Chinese herb formula improves abortion prone in mice.

BACKGROUND: Abortion prone (AP) is a common clinical event. The underlying mechanism remains unclear. Traditional Chinese formulas are known to be efficient in the management of abortion. The purpose of this study is to observe the effects of Anzitiaochongtang (AZT), a traditional formulation of Chinese medicine, on improving AP in mice by regulating immune tolerance. METHODS: An established abortion model (CBA/J×DBA/2) was employed. AZT was prepared and administered to mice in a manner consistent with clinical practice. Tolerogenic dendritic cells (tDC) and type 1 regulatory T cells (Tr1 cell) in mice were analyzed by immunological approaches to be used as representative immune tolerant parameters. RESULTS: An AP model was established with CBA/J × DBA/2 mice. The expression of IL-10 in tDC and Tr1 cell frequency in the mouse decidua tissues were lower in the AP group than that in the normal pregnancy (NP) group. Administration of AZT up regulated the expression of IL-10 in tDCs and Tr1 cell generation in the decidua tissues, and improved the pregnancy and tissue structure in AP mice. The main mechanism by which AZT improves pregnancy in AP mice is that AZT enhanced the expression of galectin-9 in the epithelial cells of decidua tissues. Galectin 9 activates TIM3 on DCs to promote the IL-10 expression. The DCs induced more Tr1 cells in the decidua tissues. CONCLUSIONS: Dysfunctional tDCs were detected in the AP decidua tissues. Administration of AZT improved pregnancy in AP mice by regulating tDC function and generation of Tr1 cells in the maternal-fetal interface.

O-GlcNAc-Mediated Regulation of Galectin Expression and Secretion in Human Promyelocytic HL-60 Cells Undergoing Neutrophilic Differentiation.

In this study, we have tested the hypothesis that the expression and secretion of galectins are driven through mechanisms globally impacted by homeostatic regulation involving the post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc). We showed that neutrophilic differentiation of HL-60 cells induced by all-trans retinoic acid (ATRA) and 6-diazo-5-oxo-L-norleucine (DON) was associated with a significant drop of cellular O-GlcNAc levels in serum-contained and serum-free cell culture media. Galectin gene and protein expression profiles in HL-60 cells were specifically modified by ATRA and by inhibitors of O-GlcNAc cycle enzymes, however overall trends for each drug were similar between cells growing in the presence or absence of serum except for LGALS9 and LGALS12. The secretion of four galectins (-1, -3, -9, and -10) by HL-60 cells in a serum-free medium was stimulated by O-GlcNAc-reducing ATRA and DON while O-GlcNAc-elevating thiamet G (O-GlcNAcase inhibitor) failed to change the basal levels of extracellular galectins. Taken together, these results demonstrate that O-GlcNAc homeostasis is essential not only for regulation of galectin expression in cells but also for the secretion of multiple members of this protein family, which can be an important novel aspect of unconventional secretion mechanisms.

Design, Synthesis, and Anticancer Activity of a Selenium-Containing Galectin-3 and Galectin-9N Inhibitor.

Galectins are soluble ß-D-galactoside-binding proteins whose implication in cancer progression and disease outcome makes them prominent targets for therapeutic intervention. In this frame, the development of small inhibitors that block selectively the activity of galectins represents an important strategy for cancer therapy which is, however, still relatively underdeveloped. To this end, we designed here a rationally and efficiently novel diglycosylated compound, characterized by a selenoglycoside bond and the presence of a lipophilic benzyl group at both saccharide residues. The relatively high binding affinity of the new compound to the carbohydrate recognition domain of two galectins, galectin 3 and galectin 9, its good antiproliferative and anti-migration activity towards melanoma cells, as well as its anti-angiogenesis properties, pave the way for its further development as an anticancer agent.

The Complex Biological Effects of Pectin: Galectin-3 Targeting as Potential Human Health Improvement?

Galectin-3 is the only chimeric representative of the galectin family. Although galectin-3 has ubiquitous regulatory and physiological effects, there is a great number of pathological environments where galectin-3 cooperatively participates. Pectin is composed of different chemical structures, such as homogalacturonans, rhamnogalacturonans, and side chains. The study of pectin's major structural aspects is fundamental to predicting the impact of pectin on human health, especially regarding distinct molecular modulation. One of the explored pectin's biological activities is the possible galectin-3 protein regulation. The present review focuses on revealing the structure/function relationship of pectins, their fragments, and their biological effects. The discussion highlighted by this review shows different effects described within in vitro and in vivo experimental models, with interesting and sometimes contradictory results, especially regarding galectin-3 interaction. The review demonstrates that pectins are promissory food-derived molecules for different bioactive functions. However, galectin-3 inhibition by pectin had been stated in literature before, although it is not a fully understood, experimentally convincing, and commonly agreed issue. It is demonstrated that more studies focusing on structural analysis and its relation to the observed beneficial effects, as well as substantial propositions of cause and effect alongside robust data, are needed for different pectin molecules' interactions with galectin-3.

Recent perspective on cow's milk allergy and dairy nutrition.

Cow's milk is a highly nutritious biological fluid that provides nourishment and immunity to infants when breastfeeding declines. However, some infants, children, and adults are allergic to cow's milk because milk contains potential allergens in the form of proteins. Casein and whey proteins and their coagulated sub-fractions in the milk such as αS1-casein, αS2-casein, ß-casein, κ-casein and α-lactalbumin, ß-lactoglobulin, bovine serum albumin, immunoglobulins, lactoferrin, respectively are the major etiological determinant of cow's milk allergy (CMA). Moreover, milk processing techniques such as homogenization and pasteurization alter the milk fat and whey protein's molecular structure and serve them as allergens to the immune system of allergic individuals. Strict exclusion of nutrient-rich milk and other dairy products from diet puts children with CMA at higher nutritional risk. Thus, regular nutritional monitoring, the inclusion of protein and mineral-rich supplements as a substitute for cow's milk, management of animal genetics (sheep, goats, buffaloes, camel, mare, donkey, yak), and milk processing to produce non-allergenic milk by inactivating allergic proteins for designer nutrition is essentially required. This review paper details the prevalence, molecular profiling of milk allergens (proteins), body immune response against CMA, consequences of milk processing, treatment, and novel role of galectins as potentially allergy suppressors.

A translational study of Galectin-3 as an early biomarker and potential therapeutic target for ischemic-reperfusion induced acute kidney injury.

PURPOSE: We evaluated Galectin-3 (Gal-3) as a potential early biomarker of acute kidney disease (AKI), and the effect of Gal-3 inhibition by modified citrus pectin (P-MCP) on renal ischemia/reperfusion (I/R) induced AKI. METHODS: Among fifty-two post-cardiac surgery patients, serum and urine Gal-3 levels were examined on intensive care unit (ICU) admission. In a rat renal I/R injury model, Gal-3 levels, renal function, and histopathology were evaluated in rats pretreated with P-MCP for one week (n = 16) compared to controls (n = 16). RESULTS: Among post-cardiac surgery patients, median serum and urine Gal-3 levels on ICU admission were higher in patients who developed AKI than those who did not (AKI vs non-AKI serum: 18.37 vs. 8.08 ng/ml, p < 0.001; AKI vs non-AKI urine:13.27 vs. 6.27 ng/ml, p < 0.001). Serum and urine Gal-3 levels were reliable biomarkers for detecting AKI (AUC: 0.88 and 0.87). In the rat renal I/R injury model, I/R caused an increase of Gal-3 at 0.5 h after reperfusion (p < 0.05). Gal-3 inhibition by P-MCP significantly decreased Gal-3 release and expression (p < 0.05), reduced interleukin (IL-6) release (p < 0.05), decreased renal dysfunction, and reduced renal tubular injury. CONCLUSIONS: Gal-3 is a potential early biomarker in the diagnosis of AKI. Inhibition of Gal-3 may provide therapeutic utility in the treatment of I/R-induced AKI.

Enhancing clinical and immunological effects of anti-PD-1 with belapectin, a galectin-3 inhibitor.

BACKGROUND: PD-1/PD-L1 engagement and overexpression of galectin-3 (Gal-3) are critical mechanisms of tumor-induced immune suppression that contribute to immunotherapy resistance. We hypothesized that Gal-3 blockade with belapectin (GR-MD-02) plus anti-PD-1 (pembrolizumab) would enhance tumor response in patients with metastatic melanoma (MM) and head and neck squamous cell carcinoma (HNSCC). METHODS: We performed a phase I dose escalation study of belapectin+pembrolizumab in patients with advanced MM or HNSCC (NCT02575404). Belapectin was administered at 2, 4, or 8 mg/kg IV 60 min before pembrolizumab (200 mg IV every 3 weeks for five cycles). Responding patients continued pembrolizumab monotherapy for up to 17 cycles. Main eligibility requirements were a functional Eastern Cooperative Oncology Group status of 0-2, measurable or assessable disease, and no active autoimmune disease. Prior T-cell checkpoint antibody therapy was permitted. RESULTS: Objective response was observed in 50% of MM (7/14) and and 33% of HNSCC (2/6) patients. Belapectin+pembrolizumab was associated with fewer immune-mediated adverse events than anticipated with pembrolizumab monotherapy. There were no dose-limiting toxicities for belapectin within the dose range investigated. Significantly increased effector memory T-cell activation and reduced monocytic myeloid-derived suppressor cells (M-MDSCs) were observed in responders compared with non-responders. Increased baseline expression of Gal-3+ tumor cells and PD-1+CD8+ T cells in the periphery correlated with response as did higher serum trough levels of pembrolizumab. CONCLUSIONS: Belapectin+pembrolizumab therapy has activity in MM and HNSCC. Increased Gal-3 expression, expansion of effector memory T cells, and decreased M-MDSCs correlated with clinical response. Further investigation is planned.

Review of galectin-3 inhibitors in the treatment of nonalcoholic steatohepatitis.

INTRODUCTION: Galectin-3 (Gal-3) is a ß-galactoside binding protein associated with many disease pathologies, including chronic inflammation and fibrogenesis. It has been implicated in the disease severity of NASH, although its precise role is unknown. Inhibition of Gal-3 has shown to improve and prevent fibrosis progression and has now reached phase III clinical trial in NASH patients. AREAS COVERED: This discusses the role of Gal-3 in NASH. It brings together the current findings of Gal-3 in NASH and hepatic fibrosis by analyzing recent data from animal model studies and clinical trials. EXPERT OPINION: Gal-3 inhibitors, in particular, Belapectin (GR-MD-02), have shown promising results for NASH with advanced fibrosis. In a phase 2 trial, Belapectin did not meet the primary endpoint. However, a sub-analysis of Belapectin among a separate group of patients without esophageal varices showed 2 mg/kg of GR-MD-02 reduced HVPG and the development of new varices. A subsequent study is under way, aiming to replicate the positive findings in phase 2 and demonstrate greater efficacy. If Belapectin is shown to be effective, it will be coupled with other drugs that target steatohepatitis to maximize efficacy and disease reversal.

Ultrafiltration isolation, structures and anti-tumor potentials of two arabinose- and galactose-rich pectins from leaves of Aralia elata.

Two novel arabinose- and galactose-rich pectic polysaccharides, AELP-B5 (Mw, 4.25 × 104 g/mol) and B6 (Mw, 1.56 × 104 g/mol), were rapidly obtained from the leaves of Aralia elata (Miq.) Seem. with anion resin and sequenced ultrafiltration membrane columns. The structural backbone and branched chains of AELP-B5 and B6 were preliminarily elucidated by mild acid hydrolysis with HILIC-ESI--MS/MS. The planar structures and spatial configurations were further identified using UPLC-QDa and GC-MS for compositions, Smith degradation and methylation analysis, FT-IR, NMR (1H/13C, DEPT, HSQC, HMBC, COSY, NOESY and TOCSY) and SEC-MALLS-RID. (1) AELP-B5 possessed →4GalA1→ as smooth regions (HG) and a repeating disaccharide moiety of →4GalA1→2Rha1→ as hairy regions (RG-I) with a 1:5 molar ratio, whereas AELP-B6 had a distinguishing 1:1 molar ratio between the HG and RG-I; (2) complex side chains were constituted of T-α-Araf, 1,3-α-Araf, 1,5-α-Araf, T-ß-Galp, 1,3-ß-Galp, 1,4-ß-Galp, 1,6-ß-Galp, 1,3,4-ß-Galp and 1,3,4,6-ß-Galp connected at C-4 of the rhamnosyl units in RG-I of AELP-B5 and B6; and (3) both possessed highly branched and compact coil conformations. The CCK-8 assay illustrated that AELP-B6 possessed higher cytotoxicity against HepG2 and HT-29 than that of AELP-B5. Surface plasmon resonance showed the binding affinity of AELP-B6 to galectin-3 (6.488 × 10-5 M) was about 10 times stronger than that of AELP-B5 (4.588 × 10-4 M). The above findings provide a molecular structure and bioactivity basis for future potential applications of AELP in the food and medical industries.

Cowpea polyphenol extract regulates galectin gene expression in bovine blood.

Galectins (GAL) are animal lectins that play important roles in the immune response through regulation of homeostasis and immune function. Bioactive polyphenols are able to bind and regulate galectins in inflammatory diseases. Cowpea is a nutritious and polyphenol-rich legume used as feed. The objective of the study was to evaluate the effect of cowpea polyphenol extract (CPE) on galectin gene transcription and translation in bovine peripheral blood. Blood from lactating cows (n = 10) were treated with CPE (10 µg/mL) or LPS (0.1 µg/mL), and control, to measure mRNA levels of bovine LGALS1, LGALS3, LGALS9, and some innate immune response genes. Secretion of GAL-1, GAL-3 and GAL-9 in plasma were measured using ELISAs. The mRNA expression of LGALS1, LGALS3 and LGALS9 decreased post CPE exposure. CPE decreased plasma GAL-1, but had no effect on GAL-3 and GAL-9. In addition, CPE decreased expression of TNFA, COX2 and upregulated TLR2, IL10 and IL4. LPS stimulation upregulated galectin genes expression and secretion. Overall, cowpea polyphenols modulated galectin expression, particularly GAL 1 in blood. The results provide a springboard for further studies on the use of polyphenol extracts from cowpea enriched feed supplements to target specific galectin genes for improved health and production in dairy cows.

Galectin-Glycan Interactions: Guidelines for Monitoring by 77 Se NMR Spectroscopy, and Solvent (H2 O/D2 O) Impact on Binding.

Functional pairing between cellular glycoconjugates and tissue lectins like galectins has wide (patho)physiological significance. Their study is facilitated by nonhydrolysable derivatives of the natural O-glycans, such as S- and Se-glycosides. The latter enable extensive analyses by specific 77 Se NMR spectroscopy, but still remain underexplored. By using the example of selenodigalactoside (SeDG) and the human galectin-1 and -3, we have evaluated diverse 77 Se NMR detection methods and propose selective 1 H,77 Se heteronuclear Hartmann-Hahn transfer for efficient use in competitive NMR screening against a selenoglycoside spy ligand. By fluorescence anisotropy, circular dichroism, and isothermal titration calorimetry (ITC), we show that the affinity and thermodynamics of SeDG binding by galectins are similar to thiodigalactoside (TDG) and N-acetyllactosamine (LacNAc), confirming that Se substitution has no major impact. ITC data in D2 O versus H2 O are similar for TDG and LacNAc binding by both galectins, but a solvent effect, indicating solvent rearrangement at the binding site, is hinted at for SeDG and clearly observed for LacNAc dimers with extended chain length.

The acid and neutral fractions of pectins isolated from ripe and overripe papayas differentially affect galectin-3 inhibition and colon cancer cell growth.

The water-soluble fractions of pectin extracted from the pulp of ripe papayas have already been found to exert positive effects on cancer cell cultures. However, the mechanisms that lead to these beneficial effects and the pectin characteristics that exert these effects are still not well understood. Characteristics such as molecular size, monosaccharide composition and structural conformation are known as polysaccharide factors that can cause alterations in cellular response. During fruit ripening, a major polysaccharide solubilization, depolymerization, and chemical modification occur. The aims of this work are to fractionate the pectin extracted from the pulp of papayas at two stages of ripening (fourth and ninth day after harvesting) into uronic and neutral fractions and to test them for the inhibition of human recombinant galectin-3 and the inhibition of colon cancer cell growth. The structures of the fractions were chemically characterized, and the uronic fraction extracted from the fourth day after harvesting presented the best biological effects across different concentrations in both galectin-3 inhibition and viability assays. The results obtained may help to establish a relationship between the chemical structures of papaya pectins and the positive in vitro biological effects, such as inhibiting cancer cell growth.

Galectin-9 Induced by Dietary Prebiotics Regulates Immunomodulation to Reduce Atopic Dermatitis Symptoms in 1-Chloro-2,4-Dinitrobenzene (DNCB)-Treated NC/Nga Mice.

Atopic dermatitis (AD) is a skin disorder that causes chronic itch. We investigated the inhibitory effects of a mixture of prebiotic short-chain galacto-oligosaccharides and long-chain fructooligosaccharides (scGOS/lcFOS), inulin, or ß-glucan on AD development in 1-chloro-2,4- dinitrobenzene (DNCB)-treated NC/Nga mice. Mice were randomly assigned to six groups: untreated mice, AD control, positive control (DNCB-treated NC/Nga mice fed a dietary supplement of Zyrtec), and DNCB-treated NC/Nga mice fed a dietary supplement of prebiotics such as scGOS/lcFOS (T1), inulin (T2), or ß-glucan (T3). The prebiotic treatment groups (T1, T2, and T3) showed suppression of AD symptoms, Th2 cell differentiation, and AD-like skin lesions induced by DNCB. In addition, prebiotic treatment also reduced the number of microorganisms such as Firmicutes, which is associated with AD symptoms, and increased the levels of Bacteroidetes and Ruminococcaceae, which are associated with alleviation of AD symptoms. Our findings demonstrate the inhibitory effects of prebiotics on AD development by improving the Th1/Th2 cytokine balance and beneficial symbiotic microorganisms in in vitro and in vivo models.

Structure-activity relationship of Citrus segment membrane RG-I pectin against Galectin-3: The galactan is not the only important factor.

Rhamnogalacturonan I (RG-I) pectin are regarded as strong galectin-3 (Gal-3) antagonist because of galactan sidechains. The present study focused on discussing the effects of more structural regions in pectin on the anti-Gal-3 activity. The water-soluble pectin (WSP) recovered from citrus canning processing water was categorized as RG-I pectin. The controlled enzymatic hydrolysis was employed to sequentially remove the α-1,5-arabinan, homogalaturonan and ß-1,4-galactan in WSP. The Gal-3-binding affinity KD (kd/ka) of WSP and debranched pectins were calculated to be 0.32 µM, 0.48 µM, 0.56 µM and 1.93 µM. Moreover, based on the more sensitive cell line (MCF-7) model, the IC30 value of WSP was lower than these of modified pectins, indicating decreased anti-Gal-3 activity. Our results suggested that the total amount of neutral sugar sidechains, the length of arabinan and cooperation between HG and RG-I played important roles in the anti-Gal-3 activity of WSP, not the Gal/Ara ratio or RG-I/HG ratio. These results provided a new insight into structure-activity relationship of citrus segment membrane RG-I as a galectin-3 antagonist and a new functional food.

Structural analyses of the HG-type pectin from notopterygium incisum and its effects on galectins.

In the manuscript, water-soluble polysaccharides WPNI was extracted from notopterygium incisum roots and separated into two homogeneous fractions WPNI-A-a and WPNI-A-b. WPNI-A-a was an arabinogalactan (AG). WPNI-A-b belonged to HG type pectin. The structure of WPNI-A-b was analyzed by FT-IR, NMR, enzymatic hydrolysis (Endo-PG) and UPLC-FLD-MSn. WPNI-A-b was dominated by HG domain, covalently linked with AG and RG-II domains. Oligogalacturonides produced by Endo-PG from HG domain were non-, mono-, di- or tri-methyl esterified with degree of polymerization (DP) from 1 to 6. The distribution of methyl-ester groups was in a block-wise manner. The interaction of WPNI-A-b and its enzymatic hydrolysis products with galectin-1, galectin-3, galectin-7 and galectin-8 showed that AG domain exhibited stronger binding avidity to galectins than RG-II and HG domain, while oligogalacturonides showed no binding activities to galectins. The results would be useful for the application of the pectin from notopterygium incisum.

Plant-derived saccharides and their inhibitory potential on metastasis associated cellular processes of pancreatic ductal adenocarcinoma cells.

This study intends to investigate the inhibitory potential of different plant derived saccharides on cell migration and adhesion of pancreatic ductal adenocarcinoma (PDAC) cells to microvascular liver endothelium, particularly considering the role of transmembranous galectin-3. PDAC cell lines PancTu1 and Panc1 were characterized by considerable (transmembranous) galectin-3 (Gal3) expression. SiRNA mediated Gal3 knockdown as well as treatment with differentially processed pectins and arabinogalactan-proteins (AGPs) did not impact on cell migration of either PDAC cell line. In contrast, Gal3 knockdown reduced adhesion of PDAC cells to the liver endothelial cell line TMNK-1 being more pronounced in Panc1 cells. Similarly, plant derived substances did not impact cell adhesion of PancTu1 cells while partially hydrolyzed citrus pectin (MCP), pectinase-treated MCP (MCPPec) and partially hydrolized AGP (AGPTFA) clearly diminished adhesive properties of Panc1 cells. MCPPec or AGPTFA could not further intensify the adhesion reducing effect of galectin-3 knockdown, indicating that these plant derived polysaccharides are able to inhibit PDAC cell adhesion to liver endothelial cells in a galectin-3 dependent manner. Overall, these data suggest an inhibitory potential of plant derived processed saccharides which have undergone chemical modification in impairing PDAC cell adhesion to liver endothelium.

Imaging, biomarker and invasive assessment of diffuse left ventricular myocardial fibrosis in atrial fibrillation.

BACKGROUND: Using cardiovascular magnetic resonance imaging (CMR), it is possible to detect diffuse fibrosis of the left ventricle (LV) in patients with atrial fibrillation (AF), which may be independently associated with recurrence of AF after ablation. By conducting CMR, clinical, electrophysiology and biomarker assessment we planned to investigate LV myocardial fibrosis in patients undergoing AF ablation. METHODS: LV fibrosis was assessed by T1 mapping in 31 patients undergoing percutaneous ablation for AF. Galectin-3, coronary sinus type I collagen C terminal telopeptide (ICTP), and type III procollagen N terminal peptide were measured with ELISA. Comparison was made between groups above and below the median for LV extracellular volume fraction (ECV), followed by regression analysis. RESULTS: On linear regression analysis LV ECV had significant associations with invasive left atrial pressure (Beta 0.49, P = 0.008) and coronary sinus ICTP (Beta 0.75, P < 0.001), which remained significant on multivariable regression. CONCLUSION: LV fibrosis in patients with AF is associated with left atrial pressure and invasively measured levels of ICTP turnover biomarker.

Oral Administration of Fucoidan Can Exert Anti-Allergic Activity after Allergen Sensitization by Enhancement of Galectin-9 Secretion in Blood.

A previous study revealed that fucoidan inhibited mast cell degranulation through the upregulation of galectin-9 in blood. The purpose of this study is to elucidate its mechanism using ovalbumin (OVA) induced anaphylaxis model mice (BALB/c, Female, 5-week-old) and mast cell line (RBL-2H3 cells). Oral administration of fucoidan after sensitization with OVA/Al(OH)3 inhibited reduction of rectal temperature induced by activation of mast cells. Fucoidan increased galectin-9 mRNA expression only in colonic epithelial cells. These results suggested that fucoidan could suppress the allergic symptoms in sensitized mice by inducing galectin-9 production from colonic epithelial cells. In addition, to check the influence of galectin 9 on the degranulation of mast cells, RBL-2H3 cell lines were treated directly with recombinant galectin-9. As expected, galectin-9 inhibited degranulation of RBL-2H3 cells pre-bound with IgE. Moreover, the residual amounts of IgE on RBL-2H3 cells were decreased by an addition of galectin-9. It was demonstrated that galectin-9 could remove IgE even if IgE was already bound to mast cells and suppress the mast cells degranulation induced by antigen. This study shows that fucoidan might become an effective therapeutic agent for patients already developed type I allergic diseases.