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Altered human gut dendritic cell properties in ulcerative colitis are reversed by Lactobacillus plantarum extracellular encrypted peptide STp.

SCOPE: The human/microbiota cross-talk is partially mediated by bacteria-derived peptides like Serine-Threonine peptide (STp), which is resistant to gut proteolysis, is found in the human healthy colon and induces regulatory properties on gut dendritic cells (DCs); here we characterized human gut DC in ulcerative colitis (UC) patients and studied the effect of STp on their properties. METHODS AND RESULTS: Human colonic DC from healthy controls and UC patients were isolated, conditioned for 24 h +/- STp and characterized by flow cytometry, immunohistochemistry, and electron microscopy. Express

[Research on ameliorating pulmonary fibrosis in silicosis mice of Cordyceps cicadae polysaccharides].

Objective: A mouse silicosis model was constructed by injecting silicon dioxide (SiO(2)) particles into the trachea to explore the effect an … e determined by Western blot. Results: The total sugar content of the CCP was 86.78%, composed of D-mannose, D-rhamnose, D-glucose and D-galactose, with a molar ratio of 12.71∶1.53∶1.00∶12.64. The infrared spectrum indicated the characteristic groups of its polysaccharides. Compared with the control group, the body weight of mice in the model group was de …

[Effects of Toxoplasma gondii type I/II rhoptry protein 16 on the polarization and inflammatory response of mouse alveolar macrophages].

OBJECTIVE: To investigate the effects of Toxoplasma gondii type I and II rhoptry protein 16 (ROP16) on the polarization and inflammatory res … RT-qPCR) assays. The expression of ROP16, inducible nitric oxide synthase (iNOS), arginase (Arg)-1, mannose receptor (CD206), cluster of differentiation 86 (CD86), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), caspase-1, apoptosis-associated speck-like protein containing a CARD (ASC), and interleukin (IL)-1β proteins was determine …

Levels of Complement Components in Children With Acute COVID-19 or Multisystem Inflammatory Syndrome.

IMPORTANCE: Multisystem inflammatory syndrome in children (MIS-C) is a severe and unrestrained inflammatory response with multiorgan involve … C3 (318.2 [70.7] ng/mL vs 237.7 [61.8] ng/mL), C5a (2614 [336.2] ng/mL vs 1826 [541.0] ng/mL), and mannose-binding lectin (79.4 [12.4] ng/mL vs 69.6 [14.7] ng/mL) in comparison to children with acute COVID-19. Levels of some of these analytes at admission (ie, pretreatment) were more elevated in children with MIS-C who needed pediatric intensive care uni …

Safety and efficacy of avalglucosidase alfa versus alglucosidase alfa in patients with late-onset Pompe disease (COMET): a phase 3, randomised, multicentre trial.

BACKGROUND: Pompe disease is a rare, progressive neuromuscular disorder caused by deficiency of acid α-glucosidase (GAA) and accumulation of lysosomal glycogen. We assessed the safety and efficacy of avalglucosidase alfa, a recombinant human GAA enzyme replacement therapy specifically designed for enhanced mannose-6-phosphate-receptor targeting and enzyme uptake aimed at increased glycogen clearance, compared with the current approved standard of care, alglucosidase alfa, in patients with late-onset Pompe disease. METHODS: We did a randomised, double-blind, phase 3 trial at 55 sites in 20 cou…

Recruitment of dendritic cells in oral lichen planus.

Using immunohistochemistry the presence of different dendritic cell (DC) subsets was analysed in 16 biopsies from patients with oral lichen planus (OLP). A significant increase of CD1a+/Langerin+ Langerhans cells, DC-SIGN+ DC and CD123+/BDCA2+ plasmacytoid DCs (PDCs) was found in the epithelium and in the stroma of OLP biopsies compared to normal oral mucosa. A proportion of DCs were mature DC-LAMP+ and expressed S100 or CD11c, typically found in the interdigitating DCs of nodal T-cell areas. Double staining revealed that mature DCs co-expressed CCR7, thus indicating the development of a nodal

Imiglucerase in the treatment of Gaucher disease: a history and perspective.

The scientific and therapeutic development of imiglucerase (Cerezyme(®)) by the Genzyme Corporation is a paradigm case for a critical examination of current trends in biotechnology. In this article the authors argue that contemporary interest in treatments for rare diseases by major pharmaceutical companies stems in large part from an exception among rarities: the astonishing commercial success of Cerezyme. The fortunes of the Genzyme Corporation, latterly acquired by global giant Sanofi SA, were founded on the evolution of a blockbuster therapy for a single but, as it turns out, propitious ul

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… The uptake into all liver cell types was inhibited by mannose-containing glycoproteins, even though the enzyme was unmodified and hepatocytes were not believed to express receptors for uptake of mannose-terminated glycoproteins. … Moreover, large mannosylated structures with a mean number of mannose residues exceeding the mean of 14 per molecule reported in imiglucerase had increased affinity for the mannose-binding lectin in serum – a humoral component of the innate immune system. …

Identification of six hub genes and analysis of their correlation with drug sensitivity in acute myeloid leukemia through bioinformatics.

BackgroundAcute myeloid leukemia (AML) is a common hematopoietic malignancy and have unsatisfactory prognosis. Our study aimed to identify hub genes in AML and explore potential biomarkers through integrated bioinformatics.MethodsMicroarray datasets were analyzed to screen the differentially expressed genes (DEGs). Functional enrichment analysis was performed, and protein-protein interaction (PPI) network was generated by the STRING (11.0) database and Cytoscape (3.7.2) software. Hub genes were screened and verified through GEPIA2 and GEO microarray database. Sensitivity of AML cell lines with

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… FLT3 , FMS-related tyrosine kinase 3; PF4 , platelet factor 4; CD163 , the macrophage scavenger receptor; MRC1 , mannose receptor C-type 1; CSF2RB , colony stimulating factor 2 receptor subunit beta; PPBP , pro-platelet basic protein; AML, acute myeloid leukemia. … MRC1 (mannose receptor C-type 1, CD206, located in 10p12.33), a member of the C-type lectin receptor family, encodes the human mannose receptor (MR). It is involved in several biological processes, including cell-cell recognition, serum glycoprotein turnover, and neutralization of pathogens. …

[Pathological changes and macrophage polarization in the liver and spleen of mice infected with Angiostrongylus cantonensis].

OBJECTIVE: To investigate the temporal changes in pathological damage and macrophage polarization in liver and spleen tissues of mice infect … umor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and M2 markers, including arginase 1 (Arg1), mannose receptor C-type 1 (Mrc1) and chitinase-like protein 3 (Chil3) was quantified in mouse liver and spleen tissues using real-time quantitative PCR (RT-qPCR) assay. RESULTS: Proliferative lesions of the hepatocyte were observed in mouse liver tissues a …

Novel Treatment Paradigms: Primary IgA Nephropathy.

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Approximately 30% to 45% of patients progress to kidney failure (KF) within 20 to 25 years of diagnosis, and there has long been a lack of effective treatments. The therapeutic landscape in IgAN is rapidly evolving, driven in large part by the acceptance of the surrogate clinical trial end point of proteinuria reduction by regulatory authorities for the accelerated approval of new therapies. Two drugs, targeted release formulation (TRF)-budesonide (nefecon) and sparsentan, have recently been approved under this sch

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… The lectin pathway (blue) is activated by mannose moieties commonly found on microbial surfaces, but also on Gd-IgA1, which bind mannose binding lectin to activate MASP1 and MASP2. MASP2 activation mirrors that of C1s, eventually leading to the formation of a C3 convertase. … Gd-IgA1, galactose deficient-IgA1; IgAN, IgA nephropathy; MASP1, mannose-binding lectin serine protease 1; MASP2, mannose-binding lectin serine protease 2. …

Biomarkers in the diagnosis of lysosomal storage disorders: proteins, lipids, and inhibodies.

A biomarker is an analyte indicating the presence of a biological process linked to the clinical manifestations and outcome of a particular disease. In the case of lysosomal storage disorders (LSDs), primary and secondary accumulating metabolites or proteins specifically secreted by storage cells are good candidates for biomarkers. Clinical applications of biomarkers are found in improved diagnosis, monitoring disease progression, and assessing therapeutic correction. These are illustrated by reviewing the discovery and use of biomarkers for Gaucher disease and Fabry disease. In addition, rece

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… This concept, named enzyme replacement therapy (ERT), is based on the principle that lysosomal proteins can reach the subcellular lysosomes via endocytosis mediated by lectins on the plasma membrane, such as the mannose 6-phosphate receptor and the mannose receptor. … The first enzyme preparation used to treat non-neuronopathic type 1 Gaucher disease consisted of placenta-derived glucocerebrosidase with modified, mannose-terminated glycans, allowing more selective uptake by tissue macrophages that are the prominent storage cells in Gaucher disease (Barton et al. 1991 …

Raised Serum Levels of Syndecan-1 (CD138), in a Case of Acute Idiopathic Systemic Capillary Leak Syndrome (SCLS) (Clarkson's Disease).

BACKGROUND Systemic capillary leak syndrome (SCLS) (Clarkson's disease) is a rare disorder of unknown etiology, characterized by transient episodes of hypotension, and the microvascular leak of fluids into the peripheral tissues, resulting in edema. Between 80-90% of patients with SCLS have a concomitant monoclonal gammopathy. Although translational in vitro studies have implicated vascular endothelial barrier dysfunction in the etiology of SCLS, the etiology and disease associations in clinical cases remain unknown. CASE REPORT We report a case of SCLS in a 49-year-old woman who initially pre

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… More extensive complement analysis performed one year later revealed lack of mannose-binding lectin (MBL), as shown in Table 2 . … Mannose-binding lectin (MBL) was low or undetectable in our patient. MBL adheres to mannose on the surface of many pathogens forming the complex, MBL-associated serine protease (MASP). …

Associations of Ficolins With Hematological Malignancies in Patients Receiving High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantations.

A prospective study of 312 patients [194 with multiple myeloma (MM) and 118 with lymphomas (LYMPH)] receiving high-dose chemotherapy and autologous hematopoietic stem cell transplantation (auto-HSCT) was conducted. Ficolins are innate immune defense factors, able to distinguish between "self" "abnormal self," and "non-self" and contribute to the elimination of the last two by direct opsonization and/or initiation of complement activation via the lectin pathway. Concentrations of ficolin-1, ficolin-2, and ficolin-3 in serially taken serum samples were determined as were the polymorphisms of the

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… The former is directly involved in recognition of pathogen/danger-associated molecular patterns, while the latter enables complexing with mannose-binding lectin-associated serine proteases (MASP). … The latter (involving mannose-binding lectin, MBL) is of particular importance in patients treated with hematopoietic stem cell transplantation (HSCT) ( 25 ). …

"Complimenting the Complement": Mechanistic Insights and Opportunities for Therapeutics in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and a leading cause of death in the US and worldwide. HCC remains a global health problem and is highly aggressive with unfavorable prognosis. Even with surgical interventions and newer medical treatment regimens, patients with HCC have poor survival rates. These limited therapeutic strategies and mechanistic understandings of HCC immunopathogenesis urgently warrant non-palliative treatment measures. Irrespective of the multitude etiologies, the liver microenvironment in HCC is intricately associated with chronic

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… Mannose Binding Lectin (MBL) Mannose-binding lectin is an important component involved in the lectin pathway of complement activation ( 235 ). … Mannose-Binding Lectin (MBL)-Associated Serine Protease-2 (MASP-2) The MBL-associated protease MASP-2 predominantly promotes activation of the lectin complement pathway. …

Immunohistochemical detection of sepsis-induced lung injury in human autopsy material.

This review addresses our present-day knowledge on the role of different cellular adhesion molecules, cytokines and glycoproteins for the de … d subepithelial seromucous glands of the bronchi. Apart from differences in binding sites for alpha-mannose, N-acetyl-neuraminic acid and alpha-(2-6)-galactose (as detected by different expression for ConA, MAA and SNA), the main finding is that no binding sites for alpha-N-acetyl-galactosamine (as investigated by MPA immunoreactivity) can be detected on …

Pertussis in high-risk groups: an overview of the past quarter-century.

Infectious diseases can impact chronic medical conditions. However, it is currently not clear how pertussis correlates with preexisting or underlying disorders. We reviewed literature from the last 25 years to describe the burden and impact of pertussis infection in specific risk groups in individuals aged ≥11 years. Our literature search returned 543 hits, of which 18 were eligible for this review. Adolescents and adults with underlying conditions, such as asthma, chronic obstructive pulmonary disease (COPD), or obesity are potentially at increased risk of pertussis infection. Immunodeficienc

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… Mannose-binding lectin (MBL) deficiency; [accessed 2019. July 16]. http://www.piduk.org/static/media/up/MBLdeficiency.pdf . 63. Dhainaut J-F, Claessens Y-E, Janes J, Nelson DR. Underlying disorders and their impact on the host response to infection. … Mannose-binding lectin (MBL) deficiency; [accessed 2019. July 16]. http://www.piduk.org/static/media/up/MBLdeficiency.pdf . Supplementary Materials Supplemental Material Click here for additional data file. …

Navigating hepatotoxicity of antibody-drug conjugates: from mechanistic insights to clinical and postmarketing evidence.

Antibody-drug conjugates (ADCs) are rapidly developing targeted cancer therapeutic agents that combine specific monoclonal antibodies with cytotoxic agents. Currently, 17 ADCs are approved for the global market for treating hematological and solid tumors with more than 100 ADCs are in phase III clinical trials. ADC-induced hepatotoxicity is a significant concern with unclear mechanisms, and the incidence of hepatic adverse events (AEs) varies across different ADCs. Most hepatic AEs are moderate; however, some ADCs can cause life threatening or fatal AEs. The management of hepatic AEs is limite

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… ADC, antibody drug-conjugate; DNA, deoxyribonucleic acid; TME, tumor microenvironment; FcγRs, Fc gamma receptors; MRs, mannose receptors; CKAP5, cytoskeleton-associated protein 5. Diagram illustrating the mechanism of antibody-drug conjugates (ADCs). … Mannose receptor and its putative ligands in normal murine lymphoid and nonlymphoid organs: in situ expression of mannose receptor by selected macrophages, endothelial cells, perivascular microglia, and mesangial cells, but not dendritic cells. J. Exp. …

Novel diagnostic options for endometriosis - Based on the glycome and microbiome.

BackgroundEndometriosis is a chronic gynaecological disease whose aetiology is still unknown. Despite its prevalence among women of reproductive age, the pathology of the disease has not yet been elucidated and only symptomatic treatment is available. Endometriosis has high latency and diagnostic methods are both limited and invasive.Aim of reviewThe aim of this review is to summarise minimally invasive or non-invasive diagnostic methods for endometriosis and their diagnostic efficiencies. Furthermore, we discuss the identification and diagnostic potential of novel disease biomarkers of microb

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… Serum mannose levels have been studied in women with polycystic ovary syndrome (PCOS) and it has been demonstrated that elevated mannose levels may be a good diagnostic marker. … Mannose receptor is highly expressed by peritoneal dendritic cells in endometriosis. Fertil Steril. 2017;107(1):167–173 e2. doi: 10.1016/j.fertnstert.2016.09.036. 135. Hirakawa T., Nasu K., Kai K., Aoyagi Y., Ishii T., Uemura T. …

Transformation in pretreatment manifestations of Gaucher disease type 1 during two decades of alglucerase/imiglucerase enzyme replacement therapy in the International Collaborative Gaucher Group (ICGG) Gaucher Registry.

This study tests the hypothesis that the prevalence of severe clinical manifestations in Gaucher disease type 1 (GD1) patients at the time of treatment initiation has changed since alglucerase/imiglucerase enzyme replacement therapy (ERT) was approved in the United States (US) in 1991. US alglucerase/imiglucerase-treated GD1 patients from the International Collaborative Gaucher Group Gaucher Registry clinicaltrials.gov NCT00358943 were stratified by age at ERT initiation (<18, 18 to <50, ≥50 years), era of ERT initiation (1991-1995, 1996-2000, 2001-2005, 2006-2009), and splenectomy status pre-

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… In 1994, following a clinical trial showing clinical equivalency of alglucerase and a recombinant version of mannose‐terminated glucocerebrosidase, 14 imiglucerase (Cerezyme ® , Sanofi Genzyme, Cambridge, MA) was approved for treatment of GD1. … Enzyme therapy in type 1 Gaucher disease: comparative efficacy of mannose‐terminated glucocerebrosidase from natural and recombinant sources . Ann Intern Med. 1995 ; 122 : 33 – 39 . 7985893 10.7326/0003-4819-122-1-199501010-00005 15 Weinreb NJ , Charrow J , Andersson HC , et al. …

Tumor-associated macrophages (TAMs) as biomarkers for gastric cancer: A review.

Gastric adenocarcinoma is one of the most common types of cancer worldwide, with an incidence of a million new cases annually. In addition to having a high mortality rate due to often delayed detection and its poor response to cancer therapy, it also spreads aggressively. Inflammation has been shown to play a role in carcinogenesis. Consequently, macrophages are important in phagocytosis, antigen presenting and producing cytokines and growth factors. As a response to microenvironmental signals, they may polarize into tumor resisting M1 or tumor promoting M2 macrophages. Recently, studies have

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… Upregulated Tim-3 is associated with lymph node metastasis, depth of tumor invasion and advanced clinical stages which suggest that Tim-3 might have an important effect in gastric cancer progression. 30 Mannose receptor (MR) can be primarily found on the surface of macrophages where it acts as an immune … Mannose receptor as a potential biomarker for gastric cancer: a pilot study Int J Biol Markers 32 2017 e278 e283 28085174 10.5301/jbm.5000244 32 Maghazachi A.A. Al-Aoukaty A. Schall T.J. …