Heparinoid Complex-Based Heparin-Binding Cytokines and Cell Delivery Carriers

Nakamura, Shingo; Sato, Yoko; Takayama, T.; Fukuda, Koichi; Fujita, Masanori; Murakami, Kaoru; Yokoe, Hidetaka

doi:10.3390/molecules24244630

Cited by 8 publications

(9 citation statements)

References 190 publications

(274 reference statements)

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“…This is a novel achievement that is different from the results of our previous work. The resulting complexes are generally referred to as "polyelectrolyte complexes (PECs)" [16,35,36], with both positive and negative surface charges. Accordingly, LHPPs appear to have similar surface conditions.…”

Section: Discussionmentioning

confidence: 99%

Development of Novel Heparin/Protamine Nanoparticles Useful for Delivery of Exogenous Proteins In Vitro and In Vivo

Nakamura

Ando

2020

Nanomaterials

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We previously reported that heparin/protamine particles (LHPPs) produced as nanoparticles through simple mixing of raw materials exhibit sustained protein release and can be retained in cells. In the present study, we modified LHPPs without employing any organic synthetic approach. The resulting LHPPs were re-named as improved LHPPs (i-LHPPs) and have the ability to retain cell-penetrating peptides (GRKKRRQRRRPPQ) based on electrostatic interactions. We examined whether i-LHPPs can introduce exogenous proteins (i.e., lacZ protein encoding bacterial β-galactosidase) into cultured cells in vitro, or into murine hepatocytes in vivo through intravenous injection to anesthetized mice. We found an accumulation of the transferred protein in both in vitro cultured cells and in vivo hepatocytes. To the best of our knowledge, reports of successful in vivo delivery to hepatocytes are rare. The i-LHPP-based protein delivery technique will be useful for in vivo functional genetic modification of mouse hepatocytes using Cas9 protein-mediated genome editing targeting specific genes, leading to the creation of hepatic disease animal models for research that aims to treat liver diseases.

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Section: Discussionmentioning

confidence: 99%

Development of Novel Heparin/Protamine Nanoparticles Useful for Delivery of Exogenous Proteins In Vitro and In Vivo

Nakamura

Ando

2020

Nanomaterials

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“…Несмотря на довольно быструю элиминацию высокомолекулярного гепарина из циркулирующей крови, достаточная длительность действия этого полиэлектролита обусловлена его способностью образовывать комплексные структуры с сигнальными молекулами [4,14]. Можно предположить, что высокомолекулярный гепарин, обладающий возможностью проходить через гематоэнцефалический барьер и воздействовать на нейромедиаторные процессы в мозге, способствовал перестройке нарушенных регуляторных механизмов гипоталамо-гипофизарно-адреналовой системы, что создало условия восстановления уровня кортикостерона [14,15].…”

Section: механизмы действия эндои экзогенного гепаринаunclassified

“…Защитные свойства ТК во многом связаны с уникальными свойствами гепарина -гликозаминогликана, присущего только ТК, который характеризуется сильно выраженной способностью об разовывать комплексные соединения со многими биологически активными веществами, в том числе с токсическими агентами, обезвреживая их. В биологическом контексте действие гепарина тесно связано с защитными реакциями при повреждении тканей и проникновении экзогенных патогенных возбудителей [4][5][6]. ТК считаются основным, если не единственным источником гепарина в организме животных и человека [7,8].…”

Section: Introductionunclassified

Mast Cells Heparin — New Information on the Old Component (Review)

Kondashevskaya

Владиславовна²

2021

Annals RAMS

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Mast cells (MC) are widely distributed throughout the body of animals and humans, mainly in barrier tissues. This review provides new information on the hematopoietic origin of MCs from early erythromyeloid progenitors (EMPs), late EMPs, and definitive hematopoietic stem cells. As well as information on the maturation of MSs and heparin synthesis already in the embryonic period. Many physiological functions of MCs are determined by the properties of heparin, which forms the basis of the matrix of granules, since the heparin molecule is a strong polyanion, capable to forming complexes with many biologically active substances and regulating their properties. In a new hypothesis about the participation of MCs in pathological processes, it is assumed that this is due to the depletion of the heparin pool. In such cases, injections of exogenous heparin can help replenish MCs heparin stores. As a result of the restoration of the physiological functions of MCs and the action of exogenous heparin, the pathological process will be converted into an adaptive one. In clinical practice, unfractionated heparin (UFH) obtained from natural sources and low molecular weight heparin (LMWH) obtained by the biochemical route are used. Most often, UFH and LMWH are used in the clinic only as anticoagulants. The worldwide spread of a disease named COVID-19 in 2020 showed that UFH and LMWH are multifunctional drugs that have saved many people. The pandemic caused by COVID-19 has been an unprecedented social and health emergency worldwide. Depression, anxiety and post-traumatic stress disorder (PTSD) have been reported in populations of many countries. This review provides new information on experimental studies on the successful treatment of pathology with low doses of UFH in modeling PTSD in animals. Consequently, heparin can be considered as a promising multifunctional drug for effective pharmacological correction of comorbid diseases under the influence of extreme factors.

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“…Moreover, derivatives of heparin have been proposed. Heparinoids constituted of heparan, dermatan, and chondroitin sulphate, are found in plants and animals, and are also of synthetic origin [ 70 ]. In the production of low molecular weight heparin, two waste heparinoids are obtained: Danaparoid and Sulodexide.…”

Section: Covid-19 Immunothrombosis and Endotheliopathymentioning

confidence: 99%

Immunothrombotic dysregulation in chagas disease and COVID-19: a comparative study of anticoagulation

et al. 2021

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Chagas and COVID-19 are diseases caused by Trypanosoma cruzi and SARS-CoV-2, respectively. These diseases present very different etiological agents despite showing similarities such as susceptibility/risk factors, pathogen-associated molecular patterns (PAMPs), recognition of glycosaminoglycans, inflammation, vascular leakage hypercoagulability, microthrombosis, and endotheliopathy; all of which suggest, in part, treatments with similar principles. Here, both diseases are compared, focusing mainly on the characteristics related to dysregulated immunothrombosis. Given the in-depth investigation of molecules and mechanisms related to microthrombosis in COVID-19, it is necessary to reconsider a prompt treatment of Chagas disease with oral anticoagulants.

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Heparinoid Complex-Based Heparin-Binding Cytokines and Cell Delivery Carriers

Cited by 8 publications

References 190 publications

Development of Novel Heparin/Protamine Nanoparticles Useful for Delivery of Exogenous Proteins In Vitro and In Vivo

Development of Novel Heparin/Protamine Nanoparticles Useful for Delivery of Exogenous Proteins In Vitro and In Vivo

Mast Cells Heparin — New Information on the Old Component (Review)

Immunothrombotic dysregulation in chagas disease and COVID-19: a comparative study of anticoagulation

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