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13 pages, 1549 KiB

Open AccessFeature PaperArticle

Extensive Tandem Duplication Events Drive the Expansion of the C1q-Domain-Containing Gene Family in Bivalves

by Marco Gerdol, Samuele Greco and Alberto Pallavicini

Mar. Drugs 2019, 17(10), 583; https://doi.org/10.3390/md17100583 - 14 Oct 2019

Cited by 28 | Viewed by 3678

Abstract

C1q-domain-containing (C1qDC) proteins are rapidly emerging as key players in the innate immune response of bivalve mollusks. Growing experimental evidence suggests that these highly abundant secretory proteins are involved in the recognition of microbe-associated molecular patterns, serving as lectin-like molecules in the bivalve [...] Read more.

C1q-domain-containing (C1qDC) proteins are rapidly emerging as key players in the innate immune response of bivalve mollusks. Growing experimental evidence suggests that these highly abundant secretory proteins are involved in the recognition of microbe-associated molecular patterns, serving as lectin-like molecules in the bivalve proto-complement system. While a large amount of functional data concerning the binding specificity of the globular head C1q domain and on the regulation of these molecules in response to infection are quickly accumulating, the genetic mechanisms that have led to the extraordinary lineage-specific expansion of the C1qDC gene family in bivalves are still largely unknown. The analysis of the chromosome-scale genome assembly of the Eastern oyster Crassostrea virginica revealed that the 476 oyster C1qDC genes, far from being uniformly distributed along the genome, are located in large clusters of tandemly duplicated paralogs, mostly found on chromosomes 7 and 8. Our observations point out that the evolutionary process behind the development of a large arsenal of C1qDC lectin-like molecules in marine bivalves is still ongoing and likely based on an unequal crossing over. Full article

(This article belongs to the Special Issue Marine Glycobiology, Glycomics and Lectins)

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14 pages, 807 KiB

Open AccessFeature PaperArticle

Effects of Crude Fucus distichus Subspecies evanescens Fucoidan Extract on Retinal Pigment Epithelium Cells―Implications for Use in Age-Related Macular Degeneration

by Kevin Rohwer, Sandesh Neupane, Kaya Saskia Bittkau, Mayra Galarza Pérez, Philipp Dörschmann, Johann Roider, Susanne Alban and Alexa Klettner

Mar. Drugs 2019, 17(9), 538; https://doi.org/10.3390/md17090538 - 16 Sep 2019

Cited by 18 | Viewed by 3588

Abstract

Fucoidan extracts may have beneficial effects in age-related macular degeneration (AMD). Over-the-counter fucoidan preparations are generally undefined, crude extracts. In this study, we investigated the effect of a crude fucoidan extract from Fucus distichus subspecies evanescens (Fe) on the retinal pigment epithelium (RPE). [...] Read more.

Fucoidan extracts may have beneficial effects in age-related macular degeneration (AMD). Over-the-counter fucoidan preparations are generally undefined, crude extracts. In this study, we investigated the effect of a crude fucoidan extract from Fucus distichus subspecies evanescens (Fe) on the retinal pigment epithelium (RPE). Fe extract was investigated for chemical composition and molar mass. It was tested in primary RPE and RPE cell line ARPE19. Oxidative stress was induced with tert-butyl hydroperoxide, cell viability evaluated with MTT assay, VEGF secretion assessed in ELISA. Phagocytosis was evaluated in a fluorescence microscopic assay. Wound healing ability was tested in a scratch assay. Additionally, the inhibition of elastase and complement system by Fe extract was studied. The Fe extract contained about 61.9% fucose and high amounts of uronic acids (26.2%). The sulfate content was not as high as expected (6.9%). It was not toxic and not protective against oxidative stress. However, Fe extract was able to reduce VEGF secretion in ARPE19. Phagocytosis was also reduced. Concerning wound healing, a delay could be observed in higher concentrations. While some beneficial effects could be found, it seems to interfere with RPE function, which may reduce its beneficial effects in AMD treatment. Full article

(This article belongs to the Special Issue Marine Glycobiology, Glycomics and Lectins)

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16 pages, 5018 KiB

Open AccessArticle

Epigenetic Modification and Differentiation Induction of Malignant Glioma Cells by Oligo-Fucoidan

by Chien-Huang Liao, I-Chun Lai, Hui-Ching Kuo, Shuang-En Chuang, Hsin-Lun Lee, Jacqueline Whang-Peng, Chih-Jung Yao and Gi-Ming Lai

Mar. Drugs 2019, 17(9), 525; https://doi.org/10.3390/md17090525 - 8 Sep 2019

Cited by 17 | Viewed by 5293

Abstract

Malignant glioma (MG) is a poor prognostic brain tumor with inevitable recurrence after multimodality treatment. Searching for more effective treatment is urgently needed. Differentiation induction via epigenetic modification has been proposed as a potential anticancer strategy. Natural products are known as fruitful sources [...] Read more.

Malignant glioma (MG) is a poor prognostic brain tumor with inevitable recurrence after multimodality treatment. Searching for more effective treatment is urgently needed. Differentiation induction via epigenetic modification has been proposed as a potential anticancer strategy. Natural products are known as fruitful sources of epigenetic modifiers with wide safety margins. We thus explored the effects of oligo-fucoidan (OF) from brown seaweed on this notion in MG cells including Grade III U87MG cells and Grade IV glioblastoma multiforme (GBM)8401 cells and compared to the immortalized astrocyte SVGp12 cells. The results showed that OF markedly suppress the proliferation of MG cells and only slightly affected that of SVGp12 cells. OF inhibited the protein expressions of DNA methyltransferases 1, 3A and 3B (DNMT1, 3A and 3B) accompanied with obvious mRNA induction of differentiation markers (MBP, OLIG2, S100β, GFAP, NeuN and MAP2) both in U87MG and GBM8401 cells. Accordingly, the methylation of p21, a DNMT3B target gene, was decreased by OF. In combination with the clinical DNMT inhibitor decitabine, OF could synergize the growth inhibition and MBP induction in U87MG cells. Appropriated clinical trials are warranted to evaluate this potential complementary approach for MG therapy after confirmation of the effects in vivo. Full article

(This article belongs to the Special Issue Marine Glycobiology, Glycomics and Lectins)

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14 pages, 2685 KiB

Open AccessArticle

MytiLec-1 Shows Glycan-Dependent Toxicity against Brine Shrimp Artemia and Induces Apoptotic Death of Ehrlich Ascites Carcinoma Cells In Vivo

by Imtiaj Hasan, A.K.M. Asaduzzaman, Rubaiya Rafique Swarna, Yuki Fujii, Yasuhiro Ozeki, Md. Belal Uddin and Syed Rashel Kabir

Mar. Drugs 2019, 17(9), 502; https://doi.org/10.3390/md17090502 - 28 Aug 2019

Cited by 11 | Viewed by 4375

Abstract

MytiLec-1, a 17 kDa lectin with β-trefoil folding that was isolated from the Mediterranean mussel (Mytilus galloprovincialis) bound to the disaccharide melibiose, Galα(1,6) Glc, and the trisaccharide globotriose, Galα(1,4) Galβ(1,4) Glc. Toxicity of the lectin was found to be low with [...] Read more.

MytiLec-1, a 17 kDa lectin with β-trefoil folding that was isolated from the Mediterranean mussel (Mytilus galloprovincialis) bound to the disaccharide melibiose, Galα(1,6) Glc, and the trisaccharide globotriose, Galα(1,4) Galβ(1,4) Glc. Toxicity of the lectin was found to be low with an LC₅₀ value of 384.53 μg/mL, determined using the Artemia nauplii lethality assay. A fluorescence assay was carried out to evaluate the glycan-dependent binding of MytiLec-1 to Artemia nauplii. The lectin strongly agglutinated Ehrlich ascites carcinoma (EAC) cells cultured in vivo in Swiss albino mice. When injected intraperitoneally to the mice at doses of 1.0 mg/kg/day and 2.0 mg/kg/day for five consecutive days, MytiLec-1 inhibited 27.62% and 48.57% of cancer cell growth, respectively. Antiproliferative activity of the lectin against U937 and HeLa cells was studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in vitro in RPMI-1640 medium. MytiLec-1 internalized into U937 cells and 50 μg/mL of the lectin inhibited their growth of to 62.70% whereas 53.59% cell growth inhibition was observed against EAC cells when incubated for 24 h. Cell morphological study and expression of apoptosis-related genes (p53, Bax, Bcl-X, and NF-κB) showed that the lectin possibly triggered apoptosis in these cells. Full article

(This article belongs to the Special Issue Marine Glycobiology, Glycomics and Lectins)

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24 pages, 3385 KiB

Open AccessArticle

The Sialic Acid-Dependent Nematocyst Discharge Process in Relation to Its Physical-Chemical Properties Is a Role Model for Nanomedical Diagnostic and Therapeutic Tools

by Ruiyan Zhang, Li Jin, Ning Zhang, Athanasios K. Petridis, Thomas Eckert, Georgios Scheiner-Bobis, Martin Bergmann, Axel Scheidig, Roland Schauer, Mingdi Yan, Samurdhi A. Wijesundera, Bengt Nordén, Barun K. Chatterjee and Hans-Christian Siebert

Mar. Drugs 2019, 17(8), 469; https://doi.org/10.3390/md17080469 - 12 Aug 2019

Cited by 11 | Viewed by 4925

Abstract

Formulas derived from theoretical physics provide important insights about the nematocyst discharge process of Cnidaria (Hydra, jellyfishes, box-jellyfishes and sea-anemones). Our model description of the fastest process in living nature raises and answers questions related to the material properties of the cell- and [...] Read more.

Formulas derived from theoretical physics provide important insights about the nematocyst discharge process of Cnidaria (Hydra, jellyfishes, box-jellyfishes and sea-anemones). Our model description of the fastest process in living nature raises and answers questions related to the material properties of the cell- and tubule-walls of nematocysts including their polysialic acid (polySia) dependent target function. Since a number of tumor-cells, especially brain-tumor cells such as neuroblastoma tissues carry the polysaccharide chain polySia in similar concentration as fish eggs or fish skin, it makes sense to use these findings for new diagnostic and therapeutic approaches in the field of nanomedicine. Therefore, the nematocyst discharge process can be considered as a bionic blue-print for future nanomedical devices in cancer diagnostics and therapies. This approach is promising because the physical background of this process can be described in a sufficient way with formulas presented here. Additionally, we discuss biophysical and biochemical experiments which will allow us to define proper boundary conditions in order to support our theoretical model approach. PolySia glycans occur in a similar density on malignant tumor cells than on the cell surfaces of Cnidarian predators and preys. The knowledge of the polySia-dependent initiation of the nematocyst discharge process in an intact nematocyte is an essential prerequisite regarding the further development of target-directed nanomedical devices for diagnostic and therapeutic purposes. The theoretical description as well as the computationally and experimentally derived results about the biophysical and biochemical parameters can contribute to a proper design of anti-tumor drug ejecting vessels which use a stylet-tubule system. Especially, the role of nematogalectins is of interest because these bridging proteins contribute as well as special collagen fibers to the elastic band properties. The basic concepts of the nematocyst discharge process inside the tubule cell walls of nematocysts were studied in jellyfishes and in Hydra which are ideal model organisms. Hydra has already been chosen by Alan Turing in order to figure out how the chemical basis of morphogenesis can be described in a fundamental way. This encouraged us to discuss the action of nematocysts in relation to morphological aspects and material requirements. Using these insights, it is now possible to discuss natural and artificial nematocyst-like vessels with optimized properties for a diagnostic and therapeutic use, e.g., in neurooncology. We show here that crucial physical parameters such as pressure thresholds and elasticity properties during the nematocyst discharge process can be described in a consistent and satisfactory way with an impact on the construction of new nanomedical devices. Full article

(This article belongs to the Special Issue Marine Glycobiology, Glycomics and Lectins)

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20 pages, 3622 KiB

Open AccessFeature PaperArticle

A Glycosaminoglycan Extract from Portunus pelagicus Inhibits BACE1, the β Secretase Implicated in Alzheimer’s Disease

by Courtney J. Mycroft-West, Lynsay C. Cooper, Anthony J. Devlin, Patricia Procter, Scott E. Guimond, Marco Guerrini, David G. Fernig, Marcelo A. Lima, Edwin A. Yates and Mark A. Skidmore

Mar. Drugs 2019, 17(5), 293; https://doi.org/10.3390/md17050293 - 16 May 2019

Cited by 10 | Viewed by 4567

Abstract

Therapeutic options for Alzheimer’s disease, the most common form of dementia, are currently restricted to palliative treatments. The glycosaminoglycan heparin, widely used as a clinical anticoagulant, has previously been shown to inhibit the Alzheimer’s disease-relevant β-secretase 1 (BACE1). Despite this, the deployment of [...] Read more.

Therapeutic options for Alzheimer’s disease, the most common form of dementia, are currently restricted to palliative treatments. The glycosaminoglycan heparin, widely used as a clinical anticoagulant, has previously been shown to inhibit the Alzheimer’s disease-relevant β-secretase 1 (BACE1). Despite this, the deployment of pharmaceutical heparin for the treatment of Alzheimer’s disease is largely precluded by its potent anticoagulant activity. Furthermore, ongoing concerns regarding the use of mammalian-sourced heparins, primarily due to prion diseases and religious beliefs hinder the deployment of alternative heparin-based therapeutics. A marine-derived, heparan sulphate-containing glycosaminoglycan extract, isolated from the crab Portunus pelagicus, was identified to inhibit human BACE1 with comparable bioactivity to that of mammalian heparin (IC₅₀ = 1.85 μg mL⁻¹ (R² = 0.94) and 2.43 μg mL⁻¹ (R² = 0.93), respectively), while possessing highly attenuated anticoagulant activities. The results from several structural techniques suggest that the interactions between BACE1 and the extract from P. pelagicus are complex and distinct from those of heparin. Full article

(This article belongs to the Special Issue Marine Glycobiology, Glycomics and Lectins)

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15 pages, 2959 KiB

Open AccessArticle

Physicochemical Characteristics and Anticoagulant Activities of the Polysaccharides from Sea Cucumber Pattalus mollis

by Wenqi Zheng, Lutan Zhou, Lisha Lin, Ying Cai, Huifang Sun, Longyan Zhao, Na Gao, Ronghua Yin and Jinhua Zhao

Mar. Drugs 2019, 17(4), 198; https://doi.org/10.3390/md17040198 - 29 Mar 2019

Cited by 38 | Viewed by 7248

Abstract

Sulfated polysaccharides from sea cucumbers possess distinct chemical structure and various biological activities. Herein, three types of polysaccharides were isolated and purified from Pattalus mollis, and their structures and bioactivities were analyzed. The fucosylated glycosaminoglycan (PmFG) had a CS-like backbone composed of [...] Read more.

Sulfated polysaccharides from sea cucumbers possess distinct chemical structure and various biological activities. Herein, three types of polysaccharides were isolated and purified from Pattalus mollis, and their structures and bioactivities were analyzed. The fucosylated glycosaminoglycan (PmFG) had a CS-like backbone composed of the repeating units of {-4-d-GlcA-β-1,3-d-GalNAc_4S6S-β-1-}, and branches of a sulfated α-l-Fuc (including Fuc_2S4S, Fuc_3S4S and Fuc_4S with a molar ratio of 2:2.5:1) linked to O-3 of each d-GlcA. The fucan sulfate (PmFS) had a backbone consisting of a repetitively linked unit {-4-l-Fuc_2S-α-1-}, and interestingly, every trisaccharide unit in its backbone was branched with a sulfated α-l-Fuc (Fuc_4S or Fuc_3S with a molar ratio of 4:1). Apart from the sulfated polysaccharides, two neutral glycans (PmNG-1 & -2) differing in molecular weight were also obtained and their structures were similar to animal glycogen. Anticoagulant assays indicated that PmFG and PmFS possessed strong APTT prolonging and intrinsic factor Xase inhibition activities, and the sulfated α-l-Fuc branches might contribute to the anticoagulant and anti-FXase activities of both PmFG and PmFS. Full article

(This article belongs to the Special Issue Marine Glycobiology, Glycomics and Lectins)

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12 pages, 3352 KiB

Open AccessArticle

Heterologous Expression of a Thermostable β-1,3-Galactosidase and Its Potential in Synthesis of Galactooligosaccharides

by Haitao Ding, Lili Zhou, Qian Zeng, Yong Yu and Bo Chen

Mar. Drugs 2018, 16(11), 415; https://doi.org/10.3390/md16110415 - 30 Oct 2018

Cited by 12 | Viewed by 3351

Abstract

A thermostable β-1,3-galactosidase from Marinomonas sp. BSi20414 was successfully heterologously expressed in Escherichia coli BL21 (DE3), with optimum over-expression conditions as follows: the recombinant cells were induced by adding 0.1 mM of IPTG to the medium when the OD₆₀₀ of the culture [...] Read more.

A thermostable β-1,3-galactosidase from Marinomonas sp. BSi20414 was successfully heterologously expressed in Escherichia coli BL21 (DE3), with optimum over-expression conditions as follows: the recombinant cells were induced by adding 0.1 mM of IPTG to the medium when the OD₆₀₀ of the culture reached between 0.6 and 0.9, followed by 22 h incubation at 20 °C. The recombinant enzyme β-1,3-galactosidase (rMaBGA) was further purified to electrophoretic purity by immobilized metal affinity chromatography and size exclusion chromatography. The specific activity of the purified enzyme was 126.4 U mg⁻¹ at 37 °C using ONPG (o-nitrophenyl-β-galactoside) as a substrate. The optimum temperature and pH of rMaBGA were determined as 60 °C and 6.0, respectively, resembling with its wild-type counterpart, wild type (wt)MaBGA. However, rMaBGA and wtMaBGA displayed different thermal stability and steady-state kinetics, although they share identical primary structures. It is postulated that the stability of the enzyme was altered by heterologous expression with the absence of post-translational modifications such as glycosylation, as well as the steady-state kinetics. To evaluate the potential of the enzyme in synthesis of galactooligosaccharides (GOS), the purified recombinant enzyme was employed to catalyze the transgalactosylation reaction at the lab scale. One of the transgalactosylation products was resolved as 3′-galactosyl-lactose, which had been proven to be a better bifidogenic effector than GOS with β-1,4 linkage and β-1,6 linkages. The results indicated that the recombinant enzyme would be a promising alternative for biosynthesis of GOS mainly with β-1,3 linkage. Full article

(This article belongs to the Special Issue Marine Glycobiology, Glycomics and Lectins)

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10 pages, 1921 KiB

Open AccessArticle

Tachypleus tridentatus Lectin Enhances Oncolytic Vaccinia Virus Replication to Suppress In Vivo Hepatocellular Carcinoma Growth

by Gongchu Li, Jianhong Cheng, Shengsheng Mei, Tao Wu and Ting Ye

Mar. Drugs 2018, 16(6), 200; https://doi.org/10.3390/md16060200 - 7 Jun 2018

Cited by 16 | Viewed by 3996

Abstract

Lectins play diverse roles in physiological processes as biological recognition molecules. In this report, a gene encoding Tachypleus tridentatus Lectin (TTL) was inserted into an oncolytic vaccinia virus (oncoVV) vector to form oncoVV-TTL, which showed significant antitumor activity in a hepatocellular carcinoma mouse [...] Read more.

Lectins play diverse roles in physiological processes as biological recognition molecules. In this report, a gene encoding Tachypleus tridentatus Lectin (TTL) was inserted into an oncolytic vaccinia virus (oncoVV) vector to form oncoVV-TTL, which showed significant antitumor activity in a hepatocellular carcinoma mouse model. Furthermore, TTL enhanced oncoVV replication through suppressing antiviral factors expression such as interferon-inducible protein 16 (IFI16), mitochondrial antiviral signaling protein (MAVS) and interferon-beta (IFN-β). Further investigations revealed that oncoVV-TTL replication was highly dependent on ERK activity. This study might provide insights into a novel way of the utilization of TTL in oncolytic viral therapies. Full article

(This article belongs to the Special Issue Marine Glycobiology, Glycomics and Lectins)

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10 pages, 1560 KiB

Open AccessArticle

Haliotis discus discus Sialic Acid-Binding Lectin Reduces the Oncolytic Vaccinia Virus Induced Toxicity in a Glioblastoma Mouse Model

by Gongchu Li, Shengsheng Mei, Jianhong Cheng, Tao Wu and Jingjing Luo

Mar. Drugs 2018, 16(5), 141; https://doi.org/10.3390/md16050141 - 26 Apr 2018

Cited by 4 | Viewed by 3948

Abstract

Although oncolytic viruses provide attractive vehicles for cancer treatment, their adverse effects are largely ignored. In this work, rat C6 glioblastoma cells were subcutaneously xenografted into mice, and a thymidine kinase-deficient oncolytic vaccinia virus (oncoVV) induced severe toxicity in this model. However, oncoVV-HddSBL, [...] Read more.

Although oncolytic viruses provide attractive vehicles for cancer treatment, their adverse effects are largely ignored. In this work, rat C6 glioblastoma cells were subcutaneously xenografted into mice, and a thymidine kinase-deficient oncolytic vaccinia virus (oncoVV) induced severe toxicity in this model. However, oncoVV-HddSBL, in which a gene encoding Haliotis discus discus sialic acid-binding lectin (HddSBL) was inserted into oncoVV, significantly prolonged the survival of mice as compared to the control virus. HddSBL reduced the tumor secreted serum rat IL-2 level upregulated by oncoVV, promoted viral replication, as well as inhibited the expression of antiviral factors in C6 glioblastoma cell line. Furthermore, HddSBL downregulated the expression levels of histone H3 and H4, and upregulated histone H3R8 and H4R3 asymmetric dimethylation, confirming the effect of HddSBL on chromatin structure suggested by the transcriptome data. Our results might provide insights into the utilization of HddSBL in counteracting the adverse effects of oncolytic vaccinia virus. Full article

(This article belongs to the Special Issue Marine Glycobiology, Glycomics and Lectins)

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Review

Jump to: Research

15 pages, 980 KiB

Open AccessReview

Therapeutic Effects of Fucoidan: A Review on Recent Studies

by Sibusiso Luthuli, Siya Wu, Yang Cheng, Xiaoli Zheng, Mingjiang Wu and Haibin Tong

Mar. Drugs 2019, 17(9), 487; https://doi.org/10.3390/md17090487 - 21 Aug 2019

Cited by 231 | Viewed by 19464

Abstract

Fucoidan is a polysaccharide largely made up of l-fucose and sulfate groups. Fucoidan is favorable worldwide, especially amongst the food and pharmaceutical industry as a consequence of its promising therapeutic effects. Its applaudable biological functions are ascribed to its unique biological structure. [...] Read more.

Fucoidan is a polysaccharide largely made up of l-fucose and sulfate groups. Fucoidan is favorable worldwide, especially amongst the food and pharmaceutical industry as a consequence of its promising therapeutic effects. Its applaudable biological functions are ascribed to its unique biological structure. Classical bioactivities associated with fucoidan include anti-oxidant, anti-tumor, anti-coagulant, anti-thrombotic, immunoregulatory, anti-viral and anti-inflammatory effects. More recently, a variety of in vitro and in vivo studies have been carried out to further highlight its therapeutic potentials. This review focuses on the progress towards understanding fucoidan and its biological activities, which may be beneficial as a future therapy. Hence, we have summarized in vitro and in vivo studies that were done within the current decade. We expect this review and a variety of others can contribute as a theoretical basis for understanding and inspire further product development of fucoidan. Full article

(This article belongs to the Special Issue Marine Glycobiology, Glycomics and Lectins)

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