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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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… In a similar drug campaign, Encysive Pharmaceuticals designed a small-molecule glycomimetic through replacement of the essential binding motifs of sLe X with a biphenyl group and mannose. …

The European Gaucher Alliance: a survey of member patient organisations' activities, healthcare environments and concerns.

BackgroundThe European Gaucher Alliance (EGA) was established in 1994 and constituted in 2008 as an umbrella group supporting patient organisations for Gaucher disease. Every two years, the EGA conducts a questionnaire survey of member associations to help develop its priorities and annual work programme. Results of the latest survey are presented.MethodsBetween June 2012 and April 2013, the 36 members and associate members of the EGA were asked to complete a questionnaire detailing membership numbers, disease specific treatments used by patients, means of access to treatment, availability of

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… The first enzyme to be used in the treatment of patients with Gaucher disease was mannose terminated human placental glucocerebrosidase, alglucerase (Ceredase®), which was replaced in 1994 by its recombinant form, imiglucerase (Cerezyme®), (both manufactured by Genzyme Corporation, Cambridge, MA, USA …

Effects of pegylated G-CSF on immune cell number and function in patients with gynecological malignancies.

BackgroundPegylated granulocyte colony-stimulating factor (G-CSF; pegfilgrastim) is a longer-acting form of G-CSF, whose effects on dendritic cell (DC) and regulatory T cell (Treg) mobilization, and on the in vivo and ex vivo release of immune modulating cytokines remain unexplored.MethodsTwelve patients with gynecological cancers received carboplatin/paclitaxel chemotherapy and single-dose pegfilgrastim as prophylaxis of febrile neutropenia. Peripheral blood was collected prior to pegfilgrastim administration (day 0) and on days +7, +11 and +21, to quantify immunoregulatory cytokines and to a

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… Dendritic cells use macropinocytosis and the mannose receptor to concentrate macromolecules in the major histocompatibility complex class II compartment: downregulation by cytokines and bacterial products. J Exp Med. 1995;182:389–400. doi: 10.1084/jem.182.2.389. …

Blood hypercoagulability and thrombosis mechanisms in cancer patients -A brief review.

Patients with malignant tumors are prone to present hypercoagulability of blood and form thrombosis, and its pathogenesis is complex involving various factors from clinical and histopathological to genetic influences. Current studies on the potential mechanism of blood hypercoagulability in patients with malignant tumors focus on the following aspects but are not limited: (1) tumor cells release coagulant-promoting substances, (2) tumor cells interact with the fibrinolytic system, (3) tumor cell-mediated platelet activation, (4) tumor-associated complement activation, and (5) genetic factors a

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… Fig. 5 Cancer-associated complement activation Cancer-associated complement is a kind of innate immune molecule, which participates in immune response and inflammation, inhibits microbial infection and the clearance of apoptotic cells through classical pathway, bypass pathway, and mannose-binding lectin …

The Potential of Mushroom Extracts to Improve Chemotherapy Efficacy in Cancer Cells: A Systematic Review.

Chemoresistance is a challenge in cancer treatment, limiting the effectiveness of chemotherapy. Mushroom extracts have shown potential as treatments for cancer therapies, offering a possible solution to overcome chemoresistance. This systematic review aimed to explore the role of mushroom extracts in enhancing chemotherapy and reversing chemoresistance in cancer cells. We searched the PubMed, Web of Science and Scopus databases, following the PRISMA guidelines, and registered on PROSPERO. The extracts acted by inhibiting the proliferation of cancer cells, as well as enhancing the effect of che

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… This process resulted in a powder known as MPSSS, which consists of glucose, galactose and mannose [ 28 ]. The team of Gou et al. [ 29 ] used polysaccharides of Trametes robiniophila Murr obtained commercially [ 29 ]. Doğan et al. [ 30 ] were the only researchers to describe collection. …

Redox Remodeling by Nutraceuticals for Prevention and Treatment of Acute and Chronic Inflammation.

Antioxidant-rich dietary regimens are considered the best practice to maintain health, control inflammation, and prevent inflammatory diseases. Yet, nutraceuticals as food supplements are self-prescribed and purchasable over the counter by healthy individuals for the purpose of beneficial effects on fitness and aging. Hence, the effectiveness, safety, and correct intake of these compounds need to be better explored. Since redox-modulating activity of these compounds appears to be involved in activation and or suppression of immune cells, the preventive use of nutraceuticals is very attractive

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… In addition, UA causes unresponsiveness in vitro of T cells from those mice even if stimulated with the polyclonal activator Concanavalin A (ConA), a mannose/glucose-binding lectin used in lymphocytes proliferation tests, as well as the associated cytokine production [ 87 ]. …

New Generation of Meso and Antiprogestins (SPRMs) into the Osteoporosis Approach.

Receptor activator of nuclear factor κB (RANK) and its ligand (RANKL) play key roles in bone metabolism and the immune system. The RANK/RANKL complex has also been shown to be critical in the formation of mammary epithelia cells. The female hormones estradiol and progesterone closely control the action of RANKL with RANK. Blood concentration of these sex hormones in the postmenopausal period leads to an increase in RANK/RANKL signaling and are a major cause of women's osteoporosis, characterized by altered bone mineralization. Knowledge of the biochemical relationships between hormones and RAN

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… A polysaccharide (DAP), isolated from the roots of Dipsacus asper Wall, which includes galactose and mannose, has been tested in ovariectomized (OVX) rats. Administration of DAP significantly prevented OVX-induced bone loss in rats. …

Heterogeneous tissue-specific macrophages orchestrate metastatic organotropism of breast cancer: implications for promising therapeutics.

Compelling evidences have manifested that breast cancer cells prefer to metastasize to certain distant organs, including brain, lung, bone and liver. According to the canonical "seed and soil" theory, this prominent biological behavior, termed as metastatic organotropism, involves intricate interactions between breast cancer cells (the "seeds") and specific residents in the tumor microenvironment (the "soil"), initiating from pre-metastatic niche formation to metastatic outgrowth. Recently, multifaceted heterogeneity of tissue-specific macrophages (TSMs) and their roles played in organotropic

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… LPS: lipopolysaccharide; MAPK: mitogen-activated protein kinase; MARCO: macrophage receptor with collagenous structure; MBC: metastatic breast cancer; MCP: monocyte chemoattractant protein; MHC: major histocompatibility complex; MIP: marophage inflammatory protein; MMP: matrix metalloproteinase; MRC: mannose … LPS: lipopolysaccharide; MAPK: mitogen-activated protein kinase; MARCO: macrophage receptor with collagenous structure; MBC: metastatic breast cancer; MCP: monocyte chemoattractant protein; MHC: major histocompatibility complex; MIP: marophage inflammatory protein; MMP: matrix metalloproteinase; MRC: mannose …

Targeting cancer stem cells with CAR-based immunotherapy: biology, evidence, and future directions.

Cancer stem cells (CSCs) are pivotal in tumor initiation, progression, and relapse, underscoring the need for targeted therapies to achieve lasting responses. This review delves into CSC biology, highlighting their tumor-initiating potential demonstrated through limiting dilution assays and their role in resistance to therapies. Although successful CAR therapies, such as anti-CD19 CAR T-cells, can induce complete responses without directly targeting CSCs, CAR strategies focusing on CSCs may offer promising avenues to prevent recurrence. We assess CAR therapies targeting CSC-specific antigens,

Convergence of mRNA technology and chimeric antigen receptor therapy: targeted technology optimizing targeted therapy.

Engineering cells to express chimeric antigen receptors (CARs) represents a novel approach in cancer immunotherapy, demonstrating remarkable efficacy in the treatment of hematologic malignancies while also encountering numerous challenges. Against the backdrop of the widespread application of COVID-19 mRNA vaccines, the integration of mRNA technology to produce CAR cells and enhance CAR therapies marks the cutting edge of cancer treatment innovation, offering potential solutions to the challenges faced by traditional CAR therapies. This convergence offers distinct advantages. It enables the ge

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… For example, dimannose on the surface of nanocarriers can specifically bind to the mannose receptor (CD206) on M2-type macrophages, enabling targeted delivery to M2 macrophages [ 111 ]. …

Nanomedicine and Onco-Immunotherapy: From the Bench to Bedside to Biomarkers.

The broad relationship between the immune system and cancer is opening a new hallmark to explore for nanomedicine. Here, all the common and synergy points between both areas are reviewed and described, and the recent approaches which show the progress from the bench to the beside to biomarkers developed in nanomedicine and onco-immunotherapy.

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… An example is mannose modification, which has an affinity for receptors present in APC [ 68 ]. Galactose modification is another example of biomimetic targeting [ 69 ]. …

Mucin1 as a potential molecule for cancer immunotherapy and targeted therapy.

Mucin1 is a highly glycosylated type 1 transmembrane mucin that ranks second among 75 tumor-related antigens published by the National Cancer Institute, and has been identified as a possible therapeutic target over the past 30 years. MUC1 plays an important role in malignant transformation and disease evolution, including cell proliferation, survival, self-renewal, and metastatic invasion. MUC1 has been shown to interact with diverse effectors such as β-catenin, receptor tyrosine kinases, and cellular-abelsongene, which are of importance in the pathogenesis of various malignant tumors. Targeti

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… A Synthetic MUC1 Anticancer Vaccine Containing Mannose Ligands for Targeting Macrophages and Dendritic Cells. ChemMedChem. 2018;13(1):25–29. doi: 10.1002/cmdc.201700646. 76. Chung MA, Luo Y, O'Donnell M, Rodriguez C, Heber W, Sharma S, Chang HR. …

Exosomes: A new option for osteoporosis treatment.

Osteoporosis is a systemic bone disease characterized by reduced bone mass and destruction of bone microarchitecture, leading to increased bone fragility and susceptibility to fracture. However, the pathogenesis and molecular mechanisms of this disease remain unclear. Extracellular vesicles, structures originating from the plasma membrane and ranging from 30 nm to 5 µm in diameter, play an important role in intercellular communication in the bone microenvironment. Exosomes are extracellular vesicles that deliver cargo molecules, including endogenous proteins, lipids and nucleic acids. These ca

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… with the ESCRT-associated protein Alix to promote late nuclear endosomal transport to lysosomes and increase exosome biogenesis. [ 20 ] Loss of Parkin function results in reduced endosomal tubulation and membrane binding of vesicular protein sorting 35 (VPS35) and sorting nexin 1, as well as reduced mannose …

CD38 Is Robustly Induced in Human Macrophages and Monocytes in Inflammatory Conditions.

Macrophages and their monocyte precursors mediate innate immune responses and can promote a spectrum of phenotypes from pro-inflammatory to pro-resolving. Currently, there are few markers that allow for robust dissection of macrophage phenotype. We recently identified CD38 as a marker of inflammatory macrophages in murine in vitro and in vivo models. However, it is unknown whether CD38 plays a similar marker and/or functional role in human macrophages and inflammatory diseases. Here, we establish that CD38 transcript and protein are robustly induced in human macrophages exposed to LPS (±IFN-γ)

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… Characterization of mannose receptor-dependent phagocytosis mediated by Mycobacterium tuberculosis lipoarabinomannan. Infect Immun (1998) 66:2769–77. 32. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. …

Parallel Toxicities: A Comparative Analysis of Chemotherapy-Induced Neutropenia and Alopecia.

Chemotherapy-induced neutropenia (CIN) and chemotherapy-induced alopecia (CIA) are significant toxicities affecting cancer patients. CIN is a potentially fatal complication of chemotherapy caused by myelosuppression and increased infection susceptibility, while CIA, although not fatal, severely affects treatment adherence and mental health. This study provides a comprehensive comparative analysis of CIN and CIA, focusing on patient, disease, treatment, and genetic risk factors. Key risk factors for CIN and CIA include age, poor performance status, body mass index (BMI), laboratory abnormalitie

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… Effects of Mannose-Binding Lectin Polymorphisms on Irinotecan-Induced Febrile Neutropenia Oncologist 2010 15 1063 1072 10.1634/theoncologist.2010-0033 20930093 PMC3227891 87. Chon S.Y. Champion R.W. Geddes E.R. Rashid R.M. Chemotherapy-Induced Alopecia J. Am. Acad. …

Taming renal inflammation: signaling pathways and therapeutic advances in lupus nephritis.

Lupus nephritis (LN), a serious complication of systemic lupus erythematosus (SLE), involves complex immune dysregulation that leads to chronic renal inflammation and progressive tissue damage. Despite decades of use of standard immunosuppressive therapy, treatment responses remain variable, and many patients experience relapses or develop end-stage renal disease. This review synthesizes emerging insights into the immunopathogenesis of LN, drawing on studies from single-cell transcriptomics, signaling pathway analyses and renal tissue immunology. It examines the role of both innate and adaptiv

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… The transition from the inflammatory state is phenotypically characterized by expression of Arg-1 and mannose receptors, and upregulation of phagocytic markers such as CD36 and MERTK, which promote apoptotic cell clearance and tissue repair [ 8 ]. …

Role of Toll-Like Receptors in Myeloid Neoplasms: Focuses on the Molecular Mechanisms and Clinical Impact on Myelodysplastic Syndromes, Acute Myeloid Leukemia, and Chronic Myeloid Leukemia.

Toll-like receptors (TLRs) are essential components of the innate immune system, functioning as pattern recognition receptors (PRRs) to detect pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). In hematological malignancies, particularly myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML), TLRs influence inflammation, disease progression, and therapeutic response. This review highlights the prognostic relevance of TLR expression, the role of the MyD88 signaling pathway in clonal evolution, and the dual

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… Some molecules can recognize these patterns and are freely soluble in plasma, such as pentraxins, a protein involved in the process of acute immune responses, as well as collections‐mannose‐binding lectin, ficolin, and the complement system, which are capable of opsonization [ 13 ]. …

Exosomes to exosome-functionalized scaffolds: a novel approach to stimulate bone regeneration.

Bone regeneration is a complex biological process that relies on the orchestrated interplay of various cellular and molecular events. Bone tissue engineering is currently the most promising method for treating bone regeneration. However, the immunogenicity, stable and cell quantity of seed cells limited their application. Recently, exosomes, which are small extracellular vesicles released by cells, have been found to effectively address these problems and better induce bone regeneration. Meanwhile, a growing line of research has shown the cargos of exosomes may provide effective therapeutic an

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… The outer layer of the exosomal phospholipid bilayer contains components such as mannose, polylactosamine, and sphingolipids, which are involved in signal recognition and maintenance of exosome morphology. …

Improving Kidney Disease Care: One Giant Leap for Nephrology.

Nephrology is an ever-evolving field of medicine. The importance of such a discipline is related to the high clinical impact of kidney disease. In fact, abnormalities of kidney function and/or structure are common in the general population, reaching an overall prevalence of about 10%. More importantly, the onset of kidney damage is related to a strikingly high risk of cardiovascular events, mortality, and progression to kidney failure which, in turn, compromises quality and duration of life. Attempts to comprehend the pathogenesis and molecular mechanisms involved in kidney disease occurrence

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… Targeting LP (Low-Grade Evidence) Binding of mannose-binding lectin (MBL), ficolins, and collectin-11 to glycosylated antigens—both on pathogens and abnormal Ig—initiates this pathway through the recruiting of specific serine-proteases (MASP1-2) which cleave C4 and C2 factors, resulting in the formation …

Novel Molecular Targets for Immune Surveillance of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a common and aggressive cancer with a high mortality rate. The incidence of HCC is increasing worldwide, and the lack of effective screening programs often results in delayed diagnosis, making it a challenging disease to manage. Immunotherapy has emerged as a promising treatment option for different kinds of cancers, with the potential to stimulate the immune system to target cancer cells. However, the current immunotherapeutic approaches for HCC have shown limited efficacy. Since HCC arises within a complex tumour microenvironment (TME) characterized by the p

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… IL-10 Down-Regulates T Cell Activation by Antigen-Presenting Liver Sinusoidal Endothelial Cells through Decreased Antigen Uptake via the Mannose Receptor and Lowered Surface Expression of Accessory Molecules Clin. Exp. …