scholarly journals Immunoadjuvant Activity of Fucoidans from the Brown Alga Fucus evanescens

Marine Drugs ◽  
2020 ◽  
Vol 18 (3) ◽  
pp. 155 ◽  
Author(s):  
Tatyana A. Kuznetsova ◽  
Tatyana P. Smolina ◽  
Ilona D. Makarenkova ◽  
Lydmila A. Ivanushko ◽  
Elena V. Persiyanova ◽  
...  
Keyword(s):  
Enzymatic Hydrolysis ◽  
Brown Alga ◽  
Structural Characteristics ◽  
Therapeutic Vaccines ◽  
Fucus Evanescens ◽  
Structural Modifications ◽  
Adjuvant Effects ◽  
Antigen Presenting

The study presents the results of a comparative evaluation of the effect of structural modifications of fucoidans from the brown alga Fucus evanescens (native, highly purified product of fucoidan enzymatic hydrolysis, a new regular 1→3;1→4-α-L-fucan, sulphated mainly at C2 and acetylated at C4 of the fucose residue) on the effector functions of innate and adaptive immunity cells in vitro and in vivo. Using flow cytometry, we found that all examined fucoidans induce the maturation of dendritic cells, enhance the ability of neutrophils to migrate and adhere, activate monocytes and enhance their antigen-presenting functions, and increase the cytotoxic potential of natural killers. Fucoidans increase the production of hepatitis B virus (HBs) specific IgG and cytokine Th1 (IFN-γ, TNF-α) and Th2 (IL-4) profiles in vivo. The data obtained suggest that in vitro and in vivo adjuvant effects of the products of fucoidan enzymatic hydrolysis with regular structural characteristics are comparable to those of the native fucoidan. Based on these data, the products of fucoidan enzymatic hydrolysis can be considered as an effective and safe candidate adjuvant to improve the efficacy of prophylactic and therapeutic vaccines.

scholarly journals The Natural Compound Hydrophobic Usnic Acid and Hydrophilic Potassium Usnate Derivative: Applications and Comparisons

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5995
Author(s):  
Hallysson Douglas Andrade de Araújo ◽  
Hianna Arely Milca Fagundes Silva ◽  
José Guedes da Silva Júnior ◽  
Mônica Camelo Pessoa de Azevedo Albuquerque ◽  
Luana Cassandra Breitenbach Barroso Coelho ◽  
...  
Keyword(s):  
Biological Activities ◽  
Structural Characteristics ◽  
Usnic Acid ◽  
Raw Material ◽  
Structural Modifications ◽  
Hydrophobic Molecule ◽  
Antiparasitic Agents ◽  
Toxic Molecule

Usnic acid is the best-studied lichen metabolite, presenting several biological activities, such as antibacterial, immunostimulating, antiviral, antifungal, anti-inflammatory, and antiparasitic agents; despite these relevant properties, it is a hydrophobic and toxic molecule. In this context, scientific research has driven the development of innovative alternatives, considering usnic acid as a source of raw material in obtaining new molecules, allowing structural modifications (syntheses) from it. The purpose is to optimize biological activities and toxicity, with less concentration and/or response time. This work presents a literature review with an analogy of the hydrophobic molecule of usnic acid with its hydrophilic derivative of potassium usnate, emphasizing the elucidation and structural characteristics, biological activities, and toxicological aspects of both molecules, and the advantages of using the promising derivative hydrophilic in different in vitro and in vivo assays when compared to usnic acid.

scholarly journals Evaluation of adjuvant effects of fucoidane from brown seaweed Fucus evanescens and its structural analogues for the strengthening vaccines effectiveness

2017 ◽  
Vol 63 (6) ◽  
pp. 553-558 ◽  
Author(s):  
T.A. Kuznetsova ◽  
L.A. Ivanushko ◽  
E.V. Persiyanova ◽  
A.L. Shutikova ◽  
S.P. Ermakova ◽  
...  
Keyword(s):  
Brown Seaweed ◽  
Sulfated Polysaccharides ◽  
Vaccine Adjuvants ◽  
Adjuvant Effect ◽  
Fucus Evanescens ◽  
Structural Modifications ◽  
B Virus ◽  
Hbs Ag ◽  
Adjuvant Effects

The use of sulfated polysaccharides from brown seaweed Fucus evanescens as adjuvants (native fucoidan in combination with polyphenols, fucoidan without polyphenols, a product of enzymatic hydrolysis of fucoidan) stimulated the formation of specific antibodies to the surface antigen of the hepatitis B virus (HBs-AG). Immunization of mice with vaccine compositions containing HBs-AG and fucoidan samples resulted in increasing the serum level of the pro-inflammatory (TNF-a, IFN-g, IL-2) cytokines. Increased production of these cytokines was detected in the culture of splenocytes additionally stimulated in vitro by fucoidans or phytohemagglutinin. The adjuvant effect of fucoidan and its structural modifications was comparable to that of the traditional licensed adjuvant aluminum hydroxide. The obtained results indicate a promising use of sulfated polysaccharides from F. evanescens as vaccine adjuvants.

Use of light microscopy in the qualitative and quantitative study of liquid crystalline order

1992 ◽  
Vol 50 (1) ◽  
pp. 264-265
Author(s):  
Christopher Viney
Keyword(s):  
Light Microscopy ◽  
Liquid Crystalline ◽  
Structural Characteristics ◽  
Molecular Order ◽  
Liquid Crystalline Phases ◽  
Convenient Technique ◽  
Liquid Crystalline Materials ◽  
Transparent Windows

Light microscopy is a convenient technique for characterizing molecular order in fluid liquid crystalline materials. Microstructures can usually be observed under the actual conditions that promote the formation of liquid crystalline phases, whether or not a solvent is required, and at temperatures that can range from the boiling point of nitrogen to 600°C. It is relatively easy to produce specimens that are sufficiently thin and flat, simply by confining a droplet between glass cover slides. Specimens do not need to be conducting, and they do not have to be maintained in a vacuum. Drybox or other controlled environmental conditions can be maintained in a sealed chamber equipped with transparent windows; some heating/ freezing stages can be used for this purpose. It is relatively easy to construct a modified stage so that the generation and relaxation of global molecular order can be observed while specimens are being sheared, simulating flow conditions that exist during processing. Also, light only rarely affects the chemical composition or molecular weight distribution of the sample. Because little or no processing is required after collecting the sample, one can be confident that biologically derived materials will reveal many of their in vivo structural characteristics, even though microscopy is performed in vitro.

scholarly journals Recent Developments in Inonotus obliquus (Chaga mushroom) Polysaccharides: Isolation, Structural Characteristics, Biological Activities and Application

Polymers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1441
Author(s):  
Yangpeng Lu ◽  
Yanan Jia ◽  
Zihan Xue ◽  
Nannan Li ◽  
Junyu Liu ◽  
...  
Keyword(s):  
Biological Activities ◽  
Structural Characteristics ◽  
Potential Candidate ◽  
Health Food ◽  
Inonotus Obliquus ◽  
Recent Developments ◽  
Inonotus Obliquus Polysaccharide ◽  
Future Work

Inonotus obliquus (Chaga mushroom) is a kind of medicine and health food widely used by folk in China, Russia, Korea, and some occidental countries. Among the extracts from Inonotus obliquus, Inonotus obliquus polysaccharide (IOPS) is supposed to be one of the major bioactive components in Inonotus obliquus, which possesses antitumor, antioxidant, anti-virus, hypoglycemic, and hypolipidemic activities. In this review, the current advancements on extraction, purification, structural characteristics, and biological activities of IOPS were summarized. This review can provide significant insight into the IOPS bioactivities as their in vitro and in vivo data were summarized, and some possible mechanisms were listed. Furthermore, applications of IOPS were reviewed and discussed; IOPS might be a potential candidate for the treatment of cancers and type 2 diabetes. Besides, new perspectives for the future work of IOPS were also proposed.

scholarly journals DNAM-1 promotes activation of cytotoxic lymphocytes by nonprofessional antigen-presenting cells and tumors

2008 ◽  
Vol 205 (13) ◽  
pp. 2965-2973 ◽  
Author(s):  
Susan Gilfillan ◽  
Christopher J. Chan ◽  
Marina Cella ◽  
Nicole M. Haynes ◽  
Aaron S. Rapaport ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Nk Cells ◽  
Adhesion Molecules ◽  
Cd8 T Cells ◽  
Nk Cell ◽  
Cd8 T Cell ◽  
Antigen Presenting

Natural killer (NK) cells and CD8 T cells require adhesion molecules for migration, activation, expansion, differentiation, and effector functions. DNAX accessory molecule 1 (DNAM-1), an adhesion molecule belonging to the immunoglobulin superfamily, promotes many of these functions in vitro. However, because NK cells and CD8 T cells express multiple adhesion molecules, it is unclear whether DNAM-1 has a unique function or is effectively redundant in vivo. To address this question, we generated mice lacking DNAM-1 and evaluated DNAM-1–deficient CD8 T cell and NK cell function in vitro and in vivo. Our results demonstrate that CD8 T cells require DNAM-1 for co-stimulation when recognizing antigen presented by nonprofessional antigen-presenting cells; in contrast, DNAM-1 is dispensable when dendritic cells present the antigen. Similarly, NK cells require DNAM-1 for the elimination of tumor cells that are comparatively resistant to NK cell–mediated cytotoxicity caused by the paucity of other NK cell–activating ligands. We conclude that DNAM-1 serves to extend the range of target cells that can activate CD8 T cell and NK cells and, hence, may be essential for immunosurveillance against tumors and/or viruses that evade recognition by other activating or accessory molecules.

scholarly journals The State of the Art and Prospects for Osteoimmunomodulatory Biomaterials

Materials ◽  
2021 ◽  
Vol 14 (6) ◽  
pp. 1357
Author(s):  
Andreea-Mariana Negrescu ◽  
Anisoara Cimpean
Keyword(s):  
Foreign Bodies ◽  
Structural Characteristics ◽  
Critical Role ◽  
Fibrous Tissue ◽  
Bioactive Molecules ◽  
New Bone Formation ◽  
Recent Developments

The critical role of the immune system in host defense against foreign bodies and pathogens has been long recognized. With the introduction of a new field of research called osteoimmunology, the crosstalk between the immune and bone-forming cells has been studied more thoroughly, leading to the conclusion that the two systems are intimately connected through various cytokines, signaling molecules, transcription factors and receptors. The host immune reaction triggered by biomaterial implantation determines the in vivo fate of the implant, either in new bone formation or in fibrous tissue encapsulation. The traditional biomaterial design consisted in fabricating inert biomaterials capable of stimulating osteogenesis; however, inconsistencies between the in vitro and in vivo results were reported. This led to a shift in the development of biomaterials towards implants with osteoimmunomodulatory properties. By endowing the orthopedic biomaterials with favorable osteoimmunomodulatory properties, a desired immune response can be triggered in order to obtain a proper bone regeneration process. In this context, various approaches, such as the modification of chemical/structural characteristics or the incorporation of bioactive molecules, have been employed in order to modulate the crosstalk with the immune cells. The current review provides an overview of recent developments in such applied strategies.

scholarly journals Transplantation-Induced Ischemia-Reperfusion Injury Modulates Antigen Presentation by Donor Renal CD11c+F4/80+ Macrophages through IL-1R8 Regulation

2020 ◽  
Vol 31 (3) ◽  
pp. 517-531 ◽  
Author(s):  
Sistiana Aiello ◽  
Manuel Alfredo Podestà ◽  
Pamela Y. Rodriguez-Ordonez ◽  
Francesca Pezzuto ◽  
Nadia Azzollini ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Antigen Presentation ◽  
Kidney Transplant ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cold Ischemia ◽  
Reversible Ischemia ◽  
Antigen Presenting

BackgroundIn donor kidneys subjected to ischemia-reperfusion injury during kidney transplant, phagocytes coexpressing the F4/80 and CD11c molecules mediate proinflammatory responses and trigger adaptive immunity in transplantation through antigen presentation. After injury, however, resident renal macrophages coexpressing these surface markers acquire a proreparative phenotype, which is pivotal in controlling inflammation and fibrosis. No data are currently available regarding the effects of transplant-induced ischemia-reperfusion injury on the ability of donor-derived resident renal macrophages to act as professional antigen-presenting cells.MethodsWe evaluated the phenotype and function of intragraft CD11c+F4/80+ renal macrophages after cold ischemia. We also assessed the modifications of donor renal macrophages after reversible ischemia-reperfusion injury in a mouse model of congeneic renal transplantation. To investigate the role played by IL-1R8, we conducted in vitro and in vivo studies comparing cells and grafts from wild-type and IL-R8–deficient donors.ResultsCold ischemia and reversible ischemia-reperfusion injury dampened antigen presentation by renal macrophages, skewed their polarization toward the M2 phenotype, and increased surface expression of IL-1R8, diminishing activation mediated by toll-like receptor 4. Ischemic IL-1R8–deficient donor renal macrophages acquired an M1 phenotype, effectively induced IFNγ and IL-17 responses, and failed to orchestrate tissue repair, resulting in severe graft fibrosis and aberrant humoral immune responses.ConclusionsIL-1R8 is a key regulator of donor renal macrophage functions after ischemia-reperfusion injury, crucial to guiding the phenotype and antigen-presenting role of these cells. It may therefore represent an intriguing pathway to explore with respect to modulating responses against autoantigens and alloantigens after kidney transplant.

scholarly journals An integrated approach to unravel a crucial structural property required for the function of the insect steroidogenic Halloween protein Noppera-bo

2020 ◽  
Vol 295 (20) ◽  
pp. 7154-7167 ◽  
Author(s):  
Kotaro Koiwai ◽  
Kazue Inaba ◽  
Kana Morohashi ◽  
Sora Enya ◽  
Reina Arai ◽  
...  
Keyword(s):  
Structural Characteristics ◽  
Integrated Approach ◽  
Binding Pocket ◽  
Loss Of Function ◽  
Tertiary Structures ◽  
Ecdysteroid Biosynthesis ◽  
17Β Estradiol ◽  
Unique Amino Acid

Ecdysteroids are the principal steroid hormones essential for insect development and physiology. In the last 18 years, several enzymes responsible for ecdysteroid biosynthesis encoded by Halloween genes were identified and genetically and biochemically characterized. However, the tertiary structures of these proteins have not yet been characterized. Here, we report the results of an integrated series of in silico, in vitro, and in vivo analyses of the Halloween GST protein Noppera-bo (Nobo). We determined crystal structures of Drosophila melanogaster Nobo (DmNobo) complexed with GSH and 17β-estradiol, a DmNobo inhibitor. 17β-Estradiol almost fully occupied the putative ligand-binding pocket and a prominent hydrogen bond formed between 17β-estradiol and Asp-113 of DmNobo. We found that Asp-113 is essential for 17β-estradiol–mediated inhibition of DmNobo enzymatic activity, as 17β-estradiol did not inhibit and physically interacted less with the D113A DmNobo variant. Asp-113 is highly conserved among Nobo proteins, but not among other GSTs, implying that this residue is important for endogenous Nobo function. Indeed, a homozygous nobo allele with the D113A substitution exhibited embryonic lethality and an undifferentiated cuticle structure, a phenocopy of complete loss-of-function nobo homozygotes. These results suggest that the nobo family of GST proteins has acquired a unique amino acid residue that appears to be essential for binding an endogenous sterol substrate to regulate ecdysteroid biosynthesis. To the best of our knowledge, ours is the first study describing the structural characteristics of insect steroidogenic Halloween proteins. Our findings provide insights relevant for applied entomology to develop insecticides that specifically inhibit ecdysteroid biosynthesis.

scholarly journals Development of Stable Chimeric IL-15 for Trans-Presentation by the Antigen Presenting Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Manoj Patidar ◽  
Naveen Yadav ◽  
Sarat K. Dalai
Keyword(s):  
T Cells ◽  
T Cell ◽  
Half Life ◽  
Therapeutic Potential ◽  
Chimeric Protein ◽  
Antigen Presenting Cells ◽  
T Cell Response ◽  
Antigen Presenting

IL-15 is one of the important biologics considered for vaccine adjuvant and treatment of cancer. However, a short half-life and poor bioavailability limit its therapeutic potential. Herein, we have structured IL-15 into a chimeric protein to improve its half-life enabling greater bioavailability for longer periods. We have covalently linked IL-15 with IgG2 base to make the IL-15 a stable chimeric protein, which also increased its serum half-life by 40 fold. The dimeric structure of this kind of IgG based biologics has greater stability, resistance to proteolytic cleavage, and less frequent dosing schedule with minimum dosage for achieving the desired response compared to that of their monomeric forms. The structured chimeric IL-15 naturally forms a dimer, and retains its affinity for binding to its receptor, IL-15Rβ. Moreover, with the focused action of the structured chimeric IL-15, antigen-presenting cells (APC) would transpresent chimeric IL-15 along with antigen to the T cell, that will help the generation of quantitatively and qualitatively better antigen-specific memory T cells. In vitro and in vivo studies demonstrate the biological activity of chimeric IL-15 with respect to its ability to induce IL-15 signaling and modulating CD8+ T cell response in favor of memory generation. Thus, a longer half-life, dimeric nature, and anticipated focused transpresentation by APCs to the T cells will make chimeric IL-15 a super-agonist for memory CD8+ T cell responses.

scholarly journals Drug reformulation for a neglected disease. The NANOHAT project to develop a safer more effective sleeping sickness drug

2021 ◽  
Vol 15 (4) ◽  
pp. e0009276
Author(s):  
Lisa Sanderson ◽  
Marcelo da Silva ◽  
Gayathri N. Sekhar ◽  
Rachel C. Brown ◽  
Hollie Burrell-Saward ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Structural Characteristics ◽  
Research Programme ◽  
Inhibitory Effect ◽  
Sleeping Sickness ◽  
Tsetse Fly ◽  
Neglected Diseases ◽  
Target Candidate Profile

Background Human African trypanosomiasis (HAT or sleeping sickness) is caused by the parasite Trypanosoma brucei sspp. The disease has two stages, a haemolymphatic stage after the bite of an infected tsetse fly, followed by a central nervous system stage where the parasite penetrates the brain, causing death if untreated. Treatment is stage-specific, due to the blood-brain barrier, with less toxic drugs such as pentamidine used to treat stage 1. The objective of our research programme was to develop an intravenous formulation of pentamidine which increases CNS exposure by some 10–100 fold, leading to efficacy against a model of stage 2 HAT. This target candidate profile is in line with drugs for neglected diseases inititative recommendations. Methodology To do this, we evaluated the physicochemical and structural characteristics of formulations of pentamidine with Pluronic micelles (triblock-copolymers of polyethylene-oxide and polypropylene oxide), selected candidates for efficacy and toxicity evaluation in vitro, quantified pentamidine CNS delivery of a sub-set of formulations in vitro and in vivo, and progressed one pentamidine-Pluronic formulation for further evaluation using an in vivo single dose brain penetration study. Principal Findings Screening pentamidine against 40 CNS targets did not reveal any major neurotoxicity concerns, however, pentamidine had a high affinity for the imidazoline2 receptor. The reduction in insulin secretion in MIN6 β-cells by pentamidine may be secondary to pentamidine-mediated activation of β-cell imidazoline receptors and impairment of cell viability. Pluronic F68 (0.01%w/v)-pentamidine formulation had a similar inhibitory effect on insulin secretion as pentamidine alone and an additive trypanocidal effect in vitro. However, all Pluronics tested (P85, P105 and F68) did not significantly enhance brain exposure of pentamidine. Significance These results are relevant to further developing block-copolymers as nanocarriers, improving BBB drug penetration and understanding the side effects of pentamidine.

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