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Lysosomal storage diseases.

Lysosomes are cytoplasmic organelles that contain a variety of different hydrolases. A genetic deficiency in the enzymatic activity of one of these hydrolases will lead to the accumulation of the material meant for lysosomal degradation. Examples include glycogen in the case of Pompe disease, glycosaminoglycans in the case of the mucopolysaccharidoses, glycoproteins in the cases of the oligosaccharidoses, and sphingolipids in the cases of Niemann-Pick disease types A and B, Gaucher disease, Tay-Sachs disease, Krabbe disease, and metachromatic leukodystrophy. Sometimes, the lysosomal storage ca

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… Unesterified cholesterol, sphingomyelin, phospholipids, and glycolipids are stored in excess in the liver and spleen, while only glycolipids are elevated in the brain. Marked storage can be seen as early as in a 20-week fetus [ 63 ]. … Consistent with the myelin loss, the white matter is evenly depleted of all lipids, particularly glycolipids. The ratio of galactocerebroside to sulfatide is abnormally high. …

Mechanistic elucidation of the therapeutic effects of Fushen Xiezhuo formula on chronic kidney disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Fushen Xiezhuo Formula (FSXZF) is a classical traditional Chinese medicine (TCM) prescription used to invigorate the spleen and reinforce the kidney, as well as to activate blood circulation and eliminate turbidity. Clinical practice has demonstrated its beneficial effects in chronic kidney disease (CKD). However, the specific bioactive constituents and molecular mechanisms responsible for its renoprotective actions remain insufficiently defined. OBJECTIVE: The active chemical components and therapeutic mechanisms of FSXZF in an adenine-induced rat model of CKD

Sophorolipids as anticancer agents: progress and challenges.

Sophorolipids (SLs) are considered effective biosurfactant for cancer treatment, which can efficiently inhibit the viability of various cancer types including breast, lung, liver, cervical and colon cancers. Their mechanism of action targets apoptosis and operates at the level of caspase enzymes, upregulation and downregulation of the B-cell lymphoma (Bcl)-family proteins, and changes in mitochondrial membrane permeability. The binding of SLs to the cancer cell receptors modulates the expression of Bax, APAF1, Bcl-2 and Bcl-x, and triggers the release of cytochrome c into the cytosol which fur

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… Phase behaviour, functionality, and physicochemical characteristics of glycolipid surfactants of microbial origin. Front Bioeng Biotechnol. 2022;10: 816613. 10.3389/fbioe.2022.816613. 24. Dabaghi S, Ataei SA, Taheri A. … Amino acid conjugated sophorolipids: a new family of biologically active functionalized glycolipids. Bioconjug Chem. 2006;17(6):1523–9. 10.1021/bc060094n. 36. Borsanyiova M, Patil A, Mukherji R, Prabhune A, Bopegamage S. …

Targeting Tumor Glycans for Cancer Therapy: Successes, Limitations, and Perspectives.

Aberrant glycosylation is a hallmark of cancer and can lead to changes that influence tumor behavior. Glycans can serve as a source of novel clinical biomarker developments, providing a set of specific targets for therapeutic intervention. Different mechanisms of aberrant glycosylation lead to the formation of tumor-associated carbohydrate antigens (TACAs) suitable for selective cancer-targeting therapy. The best characterized TACAs are truncated O-glycans (Tn, TF, and sialyl-Tn antigens), gangliosides (GD2, GD3, GM2, GM3, fucosyl-GM1), globo-serie glycans (Globo-H, SSEA-3, SSEA-4), Lewis anti

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… Aberrant glycosylation in cancer may occur in both glycoproteins and glycolipids. … Following these results, N-propionylated PSA was incorporated into a pentavalent vaccine that included four other glycolipids overexpressed in small cell lung cancer ( NCT01349647 ). 6. …

α2-3-sialylated Гликосфинголипиды при нейроинфламмации, иммунитете и запрограммированной смерти клеток: механистические доказательства и регулирование в зависимости от контекста: всеобъемлющий обзор.

α2-3-sialylated glycosphingolids (α2)3-GSLs) являются основными составляющими нейронных мембран и липидных плотов, где они формируют сепарацию рецепторов, комплекс сигналов и связь с клетками. Однако их биологическое воздействие варьируется в зависимости от молекулярного подтипа, типа клеток, стадии заболевания, концентрации и местной микроокружающей среды. В настоящем обзоре обобщены данные о перепончатых изменениях в α2-3-GSL профили и их связи с нейроинфламмацией, иммунной реакцией, протеостазом и запрограммированной клеточной смертностью через болезнь Паркинсона, болезнь Альцгеймера, болез

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… N-glycolylneuraminic acid (Neu5Gc) in bovine-derived glycolipids is also immunogenic, although its actual contribution to GBS initiation remains unclear ( 28 , 135 ). … Evidence for glycolipid antibodies in AIDP is comparatively limited, with positivity rates for conventional single-glycolipid antibodies below 15% ( 153 ). …

Carbohydrate Targets for CAR T Cells in Solid Childhood Cancers.

Application of the CAR targeting strategy in solid tumors is challenged by the need for adequate target antigens. As a consequence of their tissue origin, embryonal cancers can aberrantly express membrane-anchored gangliosides. These are carbohydrate molecules consisting of a glycosphingolipid linked to sialic acids residues. The best-known example is the abundant expression of ganglioside GD2 on the cell surface of neuroblastomas which derive from GD2-positive neuroectoderm. Gangliosides are involved in various cellular functions, including signal transduction, cell proliferation, differentia

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… Glycolipid targets: gangliosides Gangliosides were among the first antigens exploited as tumor targets for CARs. Gangliosides are complex mammalian glycolipids. They are expressed in all vertebrates and are identical in humans and in mice and other non-human species. … Carbohydrate modifications of cell surface proteins Besides membrane glycolipids, aberrant glycosylation of cell surface proteins in cancers leads to expression of distinct glycoproteins which could allow for selective CAR targeting. …

Beyond αβ T cells: NK, iNKT, and γδT cell biology in leukemic patients and potential for off-the-shelf adoptive cell therapies for AML.

Acute myeloid leukemia (AML) remains an elusive disease to treat, let alone cure, even after highly intensive therapies such as stem cell transplants. Adoptive cell therapeutic strategies based on conventional alpha beta (αβ)T cells are an active area of research in myeloid neoplasms given their remarkable success in other hematologic malignancies, particularly B-cell-derived acute lymphoid leukemia, myeloma, and lymphomas. Several limitations have hindered clinical application of adoptive cell therapies in AML including lack of leukemia-specific antigens, on-target-off-leukemic toxicity, immu

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… diverse peptides presented by MHC | NA | alpha-GalCer, other endogenous and foreign glycolipids | Limited subset HLA restriction | Yes. … These iNKT cells are highly reactive to the marine-sponge derived glycolipid α-GalCer when presented by CD1d. …

Ganglioside therapy in cancer molecular insights and therapeutic opportunities.

Gangliosides, a class of glycosphingolipids located on the plasma membrane of nearly all cells, play a crucial role in cell signaling and lipid raft dynamics. Their expression is notably high during embryonic development, markedly reduced in most adult tissues, but significantly elevated in various tumor tissues. This distinct expression pattern highlights gangliosides as promising therapeutic targets due to their roles in tumor progression, metastasis, and therapeutic resistance. Targeted ganglioside therapies, particularly monoclonal antibodies against GD2, have already demonstrated clinical

Gaucher disease: clinical profile and therapeutic developments.

Gaucher disease is a rare inborn error of glycosphingolipid metabolism due to deficiency of lysosomal acid β-glucocerebrosidase; the condition has totemic significance for the development of orphan drugs. A designer therapy, which harnesses the mannose receptor to complement the functional defect in macrophages, ameliorates the principal clinical manifestations in hematopoietic bone marrow and viscera. While several aspects of Gaucher disease (particularly those affecting the skeleton and brain) are refractory to treatment, enzyme (replacement) therapy has become a pharmaceutical blockbuster.

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… The innovation of substrate depletion therapy with biosynthetic inhibitors of the principal glycolipids, which accumulate in macrophages, provides an attractive scientific and pharmaceutical alternative. … Platt FM Neises GR Dwek RA Butters T N-butyldeoxnojirimycin is a novel inhibitor of glycolipid biosynthesis J Biol Chem 1994 269 11 8362 8365 8132559 52. …

Algae-Derived Bioactive Compounds as Platforms for Translational Biotechnology and Health Applications.

Marine macroalgae, microalgae, and associated microorganisms are increasingly recognised as valuable sources of bioactive compounds with applications across biotechnology and health. The environmental and ecological conditions they inhabit shape their metabolite diversity, leading to the production of high-value compounds such as sulphated polysaccharides, lipids, pigments, phenolics, and peptides. These compounds exhibit conserved biological activities that underpin potent antioxidant, anti-inflammatory, cytotoxic, and pro-regenerative effects with strong potential for translation. Although e

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… Collectively, these glycolipid and glycoprotein glycoconjugates contribute to macroalgae’s growing value as a source of functional biomolecules with applications in nutrition, therapeutics, and biomaterial development. 3.2.2. … Lipid-derived compounds, including sterols, glycolipids, and polyunsaturated fatty acids, also contribute to anti-inflammatory and antioxidant effects through the modulation of NF-κB, MAPK, and Nrf2 pathways. …

Therapeutic Antibodies in Cancer Treatment in the UK.

The growing understanding of the molecular mechanisms of carcinogenesis accelerated the development of monoclonal therapeutic antibodies to specifically target multiple cancer pathways. Recombinant protein therapeutics now constitute a large proportion of yearly approved medicines. Oncology, autoimmune diseases and to a smaller degree the prophylaxis of organ transplant rejection are their main application areas. As of the date of this review, 37 monoclonal antibody products are approved for use in cancer treatments in the United Kingdom. Currently, the antibody therapeutics market is dominate

Effect of PLA2G6 and SMPD1 Variants on the Lipid Metabolism in the Cerebrospinal Fluid of Patients with Parkinson's Disease: A Non-targeted Lipidomics Study.

IntroductionSleep patterns are more frequently interrupted in patients with Parkinson's disease (PD), and it is still unclear whether genetic factors are involved in PD-related sleep disorders. In this study, we hypothesize that PD-associated genetic risk affects lipid metabolism, which in turn contributes to different types of sleep disorders.MethodsWe used a non-targeted lipidomics to explore the lipid composition of cerebrospinal fluid (CSF) exosomes derived from patients with PD carrying phospholipase A2 Group VI (PLA2G6) and sphingomyelin phosphodiesterase 1 (SMPD1) mutations.ResultsPLA2G

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… High-resolution mass spectrometry showed no significant differences in glycosphingolipids, sterol lipids, lysophospholipids, and glycolipids between different SMPD1 genotypes. … Cell type-specific lipid storage changes in Parkinson's disease patient brains are recapitulated by experimental glycolipid disturbance. Proc Natl Acad Sci USA. 2020;117:27646–27654. doi: 10.1073/pnas.2003021117. 6. Shao Y, Li T, Liu Z, Wang X, Xu X, Li S, Xu G, Le W. …

Протеолипид Протеин-1 и его периферальная изоформа DM20 у пациентов с аутоиммунными расстройствами CNS.

: Антитела для протеолипидного белка-1 (PLP1-IgG), крупного центрального миелина, также выраженного в периферической нервной системе (PNS) в качестве изоформы DM20, ранее были идентифицированы главным образом у пациентов с множественным склерозом (MS), с неясными клиническими последствиями. Однако большинство исследований основывалось на неконформационных иммуномассах и охватывало лишь небольшое число пациентов с аутоиммунными расстройствами демиелионации (АДД), не относящимися к ПС CNS. Мы стремились изучить конформацию PLP1-IgG во всем спектре ОДЗ.МЕТОДЫ: Мы разработали новый анализ на основ

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… cell substrates for CBA, might account for differences in our results. 11 - 15 In a recent study, recombinant mAbs from CSF clonally expanded B cells of patients with MS were shown to bind on a specific conformational CBA, which combines PLP1 expression with increased coexpression of cholesterol and glycolipids … Second, the definition of atypical MS is arbitrary, although supported by literature data. 17 Third, PLP1-IgG conformational binding might depend on complex PLP1 epitopes that need the coexpression of cholesterol and glycolipids on CBA, 15 but we did not directly address this issue nor compared our …

Role of Ceramide from Glycosphingolipids and Its Metabolites in Immunological and Inflammatory Responses in Humans.

Glycosphingolipids (GSLs) are composed of hydrophobic ceramide and hydrophilic sugar chains. GSLs cluster to form membrane microdomains (lipid rafts) on plasma membranes, along with several kinds of transducer molecules, including Src family kinases and small G proteins. However, GSL-mediated biological functions remain unclear. Lactosylceramide (LacCer, CDw17) is highly expressed on the plasma membranes of human phagocytes and mediates several immunological and inflammatory reactions, including phagocytosis, chemotaxis, and superoxide generation. LacCer forms membrane microdomains with the Sr

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… Animal glycolipids as attachment sites for microbes Chemistry and Physics of Lipids 1986 42 1–3 153 172 10.1016/0009-3084(86)90050-2 2-s2.0-0023050967 2435422 28 Mañes S. del Real G. Martínez-A C. … Organization and functions of glycolipid-enriched microdomains in phagocytes Biochimica et Biophysica Acta 2015 1851 1 90 97 10.1016/j.bbalip.2014.06.009 2-s2.0-84911905744 24968752 91 Yuki N. …

Harnessing the Potential of Enzymes as Inhaled Therapeutics in Respiratory Tract Diseases: A Review of the Literature.

Respiratory tract diseases (RTDs) are a global cause of mortality and affect patient well-being and quality of life. Specifically, there is a high unmet need concerning respiratory tract infections (RTIs) due to limitations of vaccines and increased antibiotic resistance. Enzyme therapeutics, and in particular plant-based enzymes, represent an underutilised resource in drug development warranting further attention. This literature review aims to summarise the current state of enzyme therapeutics in medical applications, with a focus on their potential to improve outcomes in RTDs, including RTI

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… Fludase, DAS181); Remin Hospital of Wuhan University; Ansun Biopharma | In development for: severe COVID-19 (Phase N/A, NCT04324489 ) lower tract parainfluenza infection (Phase 3, NCT03808922 ) non-IFV rhinovirus infections (Phase 2, NCT04298060 ) | Catalyses sialic acid cleavage from glycoproteins and glycolipids … DAS181 is a host-directed enzyme-based drug with sialidase activity derived from bacteria, which catalyses sialic acid cleavage from glycoproteins and glycolipids in the lung epithelium thereby interfering with the life cycle of certain viruses [ 104 ]. …

Case Report: Case of subacute combiled deгенерация спинного мозга в связи с хроническим атрофическим гастритом, макроцитической анемией и положительными антисульфатидом IgM и IgG антителами.

Антисульфатидные антитела являются автоантиорганизмами, связанными с различными неврологическими расстройствами. Они были выявлены в нескольких условиях, включая синдром Гильен-Барре, множественный склероз и хронический подстрекательский демиелинизирующий полинропат. Субакустическое комбинированное дегенерирование спинного мозга вызвано главным образом дефицитом витамина В12. Хроническая атрофическая гастритис — сложное состояние, характеризующееся атрофацией и воспалением желудочно-кишечной слизи. На сегодняшний день не было зарегистрировано ни одного случая, когда пациенты с субакутальным ко

Совершенствование иммунотерапии клеток ИНКТ путем интеграции оптимизированных эндодоменов ЦАР и участников ИНКТ.

Клетки ИНКТ становятся весьма перспективной платформой иммунотерапии для лечения рака. Чтобы максимально увеличить антираковую активность CAR-INKT против рака крови, мы изучили оптимальные конструкции CAR и их комбинацию с новыми специфичными участниками INKT. Мы находим, что среди пяти различных эндодомен ЦАР, подкрепляемых возросшей вспыльчивостью и перекрестным разговором между Plexin D1 на CAR-INKT и Semaphorin 4 A на клетках миэломы, BCMA CD28z CAR-INKT проявляет наибольшую активность против миэломы. В частности, CD28z CAR-INKT опережает их коллег CAR-T. В целях расширения потенциала CAR-

Targeting the P-selectin/PSGL-1 pathway: discovery of disease-modifying therapeutics for disorders of thromboinflammation.

P-selectin is a membrane glycoprotein and a member of the selectin family of cell adhesion molecules. It is prestored in α-granules of platelets and Weibel-Palade bodies of endothelial cells and is rapidly expressed on their surfaces upon activation during the course of an inflammatory response. Although a critical component of the innate immune system, the interaction of P-selectin with its cognate ligand, P-selectin glycoprotein ligand 1 (PSGL-1) may mediate maladaptive events central to the pathophysiology of venous thromboembolism, cardiovascular disease, stroke, metabolic syndrome, and si

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… with decreased leukocyte adhesion to endothelial cells, and diminished pulmonary inflammation. 85 Polysaccharides derived from Sanguisorba officinalis , a plant in the Rosaceae family used as an herbal remedy, have also been reported to block interactions between P-selectin and PSGL-1. 86 Synthetic glycolipids … and glycopeptides Nippon Organon introduced OJ-R9188, a glycolipid mimetic consisting of a fucose and furanose glycan linked to a dipeptide and diacyl group. …

Крупная долгосрочная база данных о пациентах, страдающих болезнью Гаучера, свидетельствует о возросшем риске лимфомы и миэломы, но не твердых опухолей.

БОЛЬШЕЕ: Болезнь Гаучера (ГД) во многом связана с риском заболевания раком, причем в литературе содержатся противоречивые сообщения. Понимание истинной проблемы рака имеет решающее значение для ухода за пациентами и генетического консультирования. AIM: Определение общего и специфического риска заболевания раком в большой, одноцентровой группе GD three десятилетиями. МЕТОДЫ: Это ретроспективное когортное исследование, проведенное в национальном справочном центре. Медицинские записи 709 Пожилые пациенты из числа гинекологов >20 В Медицинском центре им. Шаара Зедека был проведен обзор. Раковые ди

Recommendations for the management of the haematological and onco-haematological aspects of Gaucher disease.

Current knowledge of the haematological and onco-haematological complications of type 1 Gaucher disease has been reviewed with the aim of identifying best clinical practice for treatment and disease management. It was concluded that: (i) Awareness of typical patterns of cytopenia can help clinicians distinguish haematological co-morbidities. (ii) Red blood cell studies and complete iron metabolism evaluation at baseline are recommended. (iii) Haemoglobin levels defining anaemia should be raised and used in Gaucher disease treatment and monitoring. (iv) Surgeons should be aware of potential ble

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… Gaucher disease and other haematological malignancies While the link between Gaucher disease and haematological malignancies other than multiple myeloma is less well-defined, it has been suggested that chronic stimulation of the immune system by stored glycolipids in Gaucher cells results in lymphoproliferation … Immune system dysfunction resulting from glycolipid storage may also influence the development of solid tumours through reduced immune surveillance due to fewer dendritic cells ( Micheva et al , 2006 ), reduced NK cell production ( Burstein et al , 1987 ), compromised T-cell proliferation and IgM secretion …