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Tumour-Derived Extracellular Vesicles (EVs): A Dangerous "Message in A Bottle" for Bone.

Several studies have shown the importance of Extracellular Vesicles (EVs) in the intercellular communication between tumour and resident cells. Through EVs, tumour cells can trigger cell-signalling molecules and shuttle exogenous information to target cells, thus promoting spread of the disease. In fact, many processes are fuelled by EVs, such as tumour invasion and dormancy, drug-resistance, immune-surveillance escape, extravasation, extracellular matrix remodelling and metastasis. A key element is certainly the molecular profile of the shed cargo. Understanding the biochemical basis of EVs w

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… EVs internalization is achieved by different mechanisms, such as clathrin-mediated endocytosis, phagocytosis, micropinocytosis, and plasma or endosomal membrane fusion, [ 110 ]. … Another suitable approach is based on the inhibition of the clathrin-mediated endocytosis pathway. Macia et al. identified an inhibitor of dinamin1/2 activity, called dynasore, able to block clathrin coats formation on the plasma membrane [ 108 ]. …

ATG5 контролирует выражение CD80 в клетках B и фигурах, соединяющих CD4+T реакции клеток.

Макроаутофагичная/аутофагическая техника была задействована в поддержке MHC класса II, но скомпрометировала MHC класса I, ограничивая представление антигена дендритическими элементами (DCs). Здесь мы сообщаем, что потеря основного аутофагического белка ATG5 в клетках B уменьшает интернализацию и стабилизирует совместное выражение поверхности CD80. В модели мыши без аутоиммунного энцефаломиелита (EAE) совместная передача индуктивных микробных клеток B (iGB) в ATG5 с клетками CD4+T, характерными для MOG, ускоренное развитие заболеваний. Блокада CD80 отменила усиленные ответные реакции CD4+T-клет

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… MHC class I internalization in DCs can be mediated by both clathrin-dependent and -independent pathways. The macroautophagy machinery has been previously suggested to support clathrin-dependent endocytosis. …

Human inhibitory leukocyte Ig-like receptors: from immunotolerance to immunotherapy.

In recent decades, immunotherapeutic strategies have been used to treat a wide range of pathologies, many of which were previously incurable, such as cancer and autoimmune disorders. Despite this unprecedented success, a considerable number of patients fail to respond to currently approved immunotherapies or develop resistance over time. Therefore, there is an urgent need to develop the next generation of immune-targeted therapies. Various members of the Ig superfamily play essential roles in regulating leukocyte functions. One such group, the leukocyte Ig-like receptors (LILRs), have been imp

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… On the other hand, coligation of LILRB4 with FcγRI on THP-1 cells inhibits FcγR-dependent uptake of antibody-opsonized bacterial particles via marked LILRB4-dependent dephosphorylation of key signaling proteins, including clathrin, SYK, and the E3 ubiquitin protein ligase CBL ( 100 ). … These results highlight LILRB4 as a regulator of signaling molecules involved in FcγRI-mediated clathrin-dependent endocytosis and phagocytosis of bacterial pathogens ( 100 ). Similarly to parasites and bacteria, viruses also seek to evade host immune responses in order to replicate ( 101 ). …

Identification of Common Differentially Expressed Genes and Potential Therapeutic Targets in Ulcerative Colitis and Rheumatoid Arthritis.

Ulcerative colitis (UC) and rheumatoid arthritis (RA) are immune-mediated inflammatory diseases (IMIDs) with similar symptoms and common genomics. However, the relationship between UC and RA has not been investigated thoroughly. Therefore, this study aimed to establish the differentially expressed genes (DEGs) and potential therapeutic targets in UC and RA. Three microarray datasets (GSE38713, GSE1919, and GSE12251) were selected from the Gene Expression Omnibus (GEO) database for analysis. We used R software to identify the DEGs and performed enrichment analyses. Search Tool for the Retrieval

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… The terms enriched under CC were external side of plasma membrane, contractile fiber part, and clathrin-coated vesicle membrane. Moreover, the terms enriched under MF were DNA-binding transcription repressor activity, coreceptor activity, and virus receptor activity ( Table 1 and Figure 2D ). … to antibiotic | 14 | 0.000109 | | GO:0051384 | Response to glucocorticoid | 10 | 0.000109 | | GO:0031960 | Response to corticosteroid | 10 | 0.000193 | CC | GO:0009897 | External side of plasma membrane | 16 | 1.88E-06 | | GO:0044449 | Contractile fiber part | 8 | 0.008248 | | GO:0030665 | Clathrin-coated …

Mathematical modeling in cancer nanomedicine: a review.

Cancer continues to be among the leading healthcare problems worldwide, and efforts continue not just to find better drugs, but also better drug delivery methods. The need for delivering cytotoxic agents selectively to cancerous cells, for improved safety and efficacy, has triggered the application of nanotechnology in medicine. This effort has provided drug delivery systems that can potentially revolutionize cancer treatment. Nanocarriers, due to their capacity for targeted drug delivery, can shift the balance of cytotoxicity from healthy to cancerous cells. The field of cancer nanomedicine h

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… Caveolin-dependent ( c ) or clathrin-dependent ( d ) endocytosis occurs by receptor-ligand binding leading to the formation of flask-shaped caveolae and clathrin-coated pits, respectively, on the cytosolic side of the cell membrane. … Although receptor-mediated endocytosis may also be clathrin- and caveolin-independent ( e ). Non-specific interactions maybe involved in endocytosis of NPs without conjugated ligands ( f ). …

Re-Cellularised Kidney Scaffold for Chikungunya Virus Propagation: A Novel Approach.

BACKGROUND: Re-emerging viral attacks are catastrophic for health and economy. It is crucial to grasp the viral life cycle, replication and mutation policies and attack strategies. It is also absolute to fathom the cost-efficient antiviral remedies earliest possible. METHODS: We propose to use a lab-grown organ (re-cellularized scaffold of sheep kidney) for viral culture and understand its interaction with extra-cellular matrices of the host tissue. RESULTS: Our findings showed that the chikungunya virus (CHIKV) could be better replicated in tissue-engineered bio models than cell culture. A

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… After entering Vero cells by clathrin-mediated endocytosis (CME), its effect on cellular and extracellular matrix (ECM) is unknown [ 4 ]. … Kirchhausen T Owen D Harrison SC Molecular structure, function, and dynamics of clathrin-mediated membrane traffic Cold Spring Harb Perspect Biol 2014 6 a016725 10.1101/cshperspect.a016725 24789820 PMC3996469 5. …

A proteomic signature of oocyte quality from models of varying oocyte developmental competence.

STUDY QUESTION: Which proteins underpin oocyte developmental competence, as modelled by oocytes of variable competence matured in vivo or ma … ukaryotic translation, autophagy, and endocytosis pathways within oocytes. Orthogonal validation of clathrin, ribosomal protein L24, and eukaryotic initiation factor 2A supported the proteomic findings, and their expression was conserved in human GV and MII oocytes. Changes in reactive oxygen species detoxification and serine biosynthesis were observed in …

Advances in Gold Nanoparticle-Based Combined Cancer Therapy.

According to the global cancer observatory (GLOBOCAN), there are approximately 18 million new cancer cases per year worldwide. Cancer therapies are largely limited to surgery, radiotherapy, and chemotherapy. In radiotherapy and chemotherapy, the maximum tolerated dose is presently being used to treat cancer patients. The integrated development of innovative nanoparticle (NP) based approaches will be a key to address one of the main issues in both radiotherapy and chemotherapy: normal tissue toxicity. Among other inorganic NP systems, gold nanoparticle (GNP) based systems offer the means to fur

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… Intracellular Fate of Gold Nanoparticles Based on Their Physicochemical Properties There are different methods of entry into cells for NPs, including clathrin-mediated endocytosis, clathrin-caveolin independent endocytosis, and caveolae-mediated endocytosis [ 63 ]. … Most NPs, including GNPs, enter the cell mostly via clathrin-mediated, or receptor-mediated, endocytosis (RME) [ 46 , 64 , 65 , 66 , 67 , 68 ]. The efficiency of the RME process depends on the interaction between molecules on the NP surface (ligands) and the cell membrane receptors. …

Growth inhibition of head and neck squamous cell carcinoma cells by sgRNA targeting the cyclin D1 mRNA based on TRUE gene silencing.

Head and neck squamous cell carcinoma (HNSCC) exhibits increased expression of cyclin D1 (CCND1). Previous studies have shown a correlation between poor prognosis of HNSCC and cyclin D1 overexpression. tRNase ZL-utilizing efficacious gene silencing (TRUE gene silencing) is one of the RNA-mediated gene expression control technologies that have therapeutic potential. This technology is based on a unique enzymatic property of mammalian tRNase ZL, which is that it can cleave any target RNA at any desired site by recognizing a pre-tRNA-like complex formed between the target RNA and an artificial sm

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… endocytosis inhibitors including chlorpromazine, nystatin or methyl-β-cyclodextrin were unable to diminish the apoptosis-inducing or target mRNA-reducing effects induced by naked sgRNA (Tamura et al., unpublished data), suggesting that functional uptake by cells in culture does not appear to be mediated by clathrin … Similar to this, Koller et al. [50] also reported that functional uptake of a single-stranded phosphorothioate-modified antisense oligonucleotide is not mediated by clathrin- or caveolin-dependent endocytosis. …

Severe Hypocalcemia and Hypomagnesemia with Denosumab in Advanced Chronic Kidney Disease: Case Report and Literature Review.

BackgroundDenosumab has become the preferred agent over zolendronic acid to help prevent skeletal-related events in patients with metastatic bone disease and multiple myeloma because it is approved for use in those with kidney dysfunction. However, denosumab has been linked to cases of hypocalcemia, particularly in those with advanced kidney disease.Case presentationWe present the case of a patient with metastatic prostate cancer and chronic kidney disease due to obstructive nephropathy who developed severe hypocalcemia and hypomagnesemia after denosumab injection, which required intensive car

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… OPG/membranous–RANKL complex is internalized via the clathrin pathway before a lysosomal and a proteasomal degradation Bone 2006 39 4 706 715 10.1016/j.bone.2006.03.016 2-s2.0-33748199511 16750945 7 Keizer R. J. Huitema A. D. R. Schellens J. H. M. Beijnen J. H. …

KIF11 promotes rheumatoid arthritis pathogenesis by activating M1 macrophage polarization and promoting inflammatory cytokine secretion.

BACKGROUND AND OBJECTIVE: KIF11, a mitotic kinesin, has been implicated in oncogenesis, but its specific role and mechanism in RA pathogenesis remain largely unexplored. We aim to explore functional role and molecular mechanism of KIF11 to promote RA progression. METHODS: Bioinformatics analysis was first performed on public RA datasets (GSE55457, GSE55235, GSE2053, GSE12021, and GSE1919) to identify KIF11-associated DEGs and their enriched pathways using GO/KEGG and GSEA analysis. Lentivirus-mediated shRNA was employed to knock down KIF11 expression in MH7A cells and M1-polarized macrophages

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… In terms of cellular components (CC), the DEGs were significantly localized to the external side of plasma membrane, clathrin-coated endocytic vesicle membrane, and clathrin-coated vesicle membrane. …

Multiple Myeloma Cell-Derived Exosomes: Implications on Tumorigenesis, Diagnosis, Prognosis and Therapeutic Strategies.

Multiple myeloma (MM) is a hematological disease that is still not curable. The bone marrow milieu, with cellular and non-cellular elements, participate in the creation of a pro-tumoral environment enhancing growth and survival of MM plasma cells. Exosomes are vesicles oscillating in dimension between 50 nm and 100 nm in size that can be released by various cells and contribute to the pathogenesis and progression of MM. Exosomes enclose proteins, cytokines, lipids, microRNAs, long noncoding RNAs, and circular RNAs able to regulate interactions between MM plasma cells and adjacent cells. Throug

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… The systems by which exosomes are taken by cells comprise phagocytosis, clathrin- or caveolin-mediated endocytosis, micropinocytosis, and lipid raft–mediated endocytosis [ 9 ]. … A different approach involved the use of shRNA-mediated knockdown of endocytosis-related proteins such as flotillin-1, caveolin-1, and clathrin heavy chain. This technique was able to reduce exosome-absorption in MM plasma cells. …

Proteomic analysis identifies pathways related to immune dysregulation in patients with hematologic malignancies after COVID-19 infection.

Patients with hematologic malignancies (HMs) are particularly vulnerable to coronavirus disease 2019 (COVID-19) because of underlying immune dysfunction and treatment-related immunosuppression. However, proteomic features associated with different clinical trajectories in this population remain insufficiently characterized. We performed serum proteomic analysis in 40 HM patients with COVID-19 and 15 healthy controls. Compared with controls, HM patients showed impaired immune-related responses during the acute phase of COVID-19. Acute-phase proteomic patterns differed across outcome groups; how

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… Notably, viral entry mediators CLTC (clathrin heavy chain) and AP1G1 (adaptor protein complex 1 gamma 1) were significantly upregulated in fatal cases compared with those with uncomplicated infections ( Fig. 3A ). … SARS-CoV-2 infects cells after viral entry via clathrin-mediated endocytosis . J Biol Chem 296 : 100306 . doi: 10.1016/j.jbc.2021.100306 33476648 PMC7816624 18 Primorac D , Vrdoljak K , Brlek P , Pavelić E , Molnar V , Matišić V , Erceg Ivkošić I , Parčina M . 2022 . …

Engineering precision nanoparticles for drug delivery.

In recent years, the development of nanoparticles has expanded into a broad range of clinical applications. Nanoparticles have been developed to overcome the limitations of free therapeutics and navigate biological barriers - systemic, microenvironmental and cellular - that are heterogeneous across patient populations and diseases. Overcoming this patient heterogeneity has also been accomplished through precision therapeutics, in which personalized interventions have enhanced therapeutic efficacy. However, nanoparticle development continues to focus on optimizing delivery platforms with a one-

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… This form of endocytosis is more common for nanorods; nanosphere uptake is usually clathrin-mediated 138 . … Clathrin-mediated endocytosis — the most common route for NP uptake in non-specialized mammalian cells — relies on receptor-mediated, hydrophobic or electrostatic interactions between NPs and the cell membrane in areas of clathrin expression 90 , 160 . …

Denosumab Related Osteonecrosis of the Jaw with Spontaneous Necrosis of the Soft Palate: Report of a Life Threatening Case.

Bisphosphonates have been used for years in the treatment of patients with distant bony metastasis and in the prevention of osteoporosis. One of main side effects of these medications is the development of bisphosphonate related osteonecrosis of the jaw (BRONJ) in a small subset of patients. A new class of medications with a shorter half-life, known as receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors, was introduced with the hopes of avoiding this side effect. However, reports of osteonecrosis of the jaw after the use of RANKL inhibitors have also been documented. We repo

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… OPG/membranous-RANKL complex is internalized via the clathrin pathway before a lysosomal and a proteasomal degradation Bone 2006 39 4 706 715 10.1016/j.bone.2006.03.016 2-s2.0-33748199511 16750945 17 Kendler D. L. Roux C. Benhamou C. L. …

The Antibody Drug Conjugate, Belantamab-Mafodotin, in the Treatment of Multiple Myeloma: A Comprehensive Review.

Despite recent advancements in treatments, including proteasome inhibitors, immunomodulators, and anti-CD38 monoclonal antibodies, multiple myeloma (MM) remains mostly incurable with patients frequently experiencing disease relapses due to therapy resistance. Hence there is an urgent need for innovative treatments for patients with relapsed and/or refractory MM (RRMM). This review examines Belantamab mafodotin, the first antibody-drug conjugate (ADC) targeting B-cell maturation antigen (BCMA), which has shown efficacy in pre-clinical and clinical settings for RRMM. BCMA, a type III transmembra

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… GSIs have improved anti-BCMA CAR-T therapy effectiveness in vivo. 59 Also, several clinical trials are exploring their combination with anti-BCMA CAR-T therapy to potentially improve anti-BCMA ADC therapy. 10 After binding to BCMA ADCs are internalized into the cell via clathrin-mediated, caveolin-mediated … , or clathrin-caveolin-independent endocytosis. …

Mesoporous Silica Nanoparticles as Drug Delivery Vehicles in Cancer.

Even though cancer treatment has improved over the recent decades, still more specific and effective treatment concepts are mandatory. Surgical removal is not always possible, metastases are challenging and chemo- and radiotherapy can not only have severe side-effects but also resistances may occur. To cope with these challenges more efficient therapies with fewer side-effects are required. One promising approach is the use of drug delivery vehicles. Here, mesoporous silica nanoparticles (MSN) are discussed as biodegradable drug carrier to improve efficacy and reduce side-effects. MSN excellen

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… In general, several possible endocytic pathways for cellular nanoparticle uptake were proposed, namely caveolae or clathrin-dependent endocytosis, caveolae or clathrin-independent endocytosis and micropinocytosis [ 27 ]. …

Iron deprivation in cancer--potential therapeutic implications.

Iron is essential for normal cellular function. It participates in a wide variety of cellular processes, including cellular respiration, DNA synthesis, and macromolecule biosynthesis. Iron is required for cell growth and proliferation, and changes in intracellular iron availability can have significant effects on cell cycle regulation, cellular metabolism, and cell division. Perhaps not surprisingly then, neoplastic cells have been found to have higher iron requirements than normal, non-malignant cells. Iron depletion through chelation has been explored as a possible therapeutic intervention i

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… Clathrin-mediated endocytosis of the Tf-TfR1 complex is the primary mechanism by which cells are able to take up iron. Once internalized, iron dissociates from Tf as a result of acidification of the endosome and is released into the cytosol through DMT1 [ 4 ]. … Iron laden transferrin is taken up by the cell via clathrin-mediated endocytosis of transferrin receptor-1 (TfR1). Acidification of the resultant endosome releases iron from TfR. Iron is transported out of the endosome via DMT1, and becomes part of the labile iron pool. …

Extranodal diffuse large B-cell lymphoma with monoclonal gammopathy: an aggressive and primary refractory disease responding to an immunomodulatory agent.

BackgroundAlthough the clinical outcome of patients with diffuse large B cell lymphoma (DLBCL) has been improved by the addition of rituximab to standard chemotherapy, almost one-third fails or relapses after first line treatment. The presence of monoclonal gammopathy (MG) is a known adverse prognostic factor for DLBCL. Because this subset of patients does not benefit from R-CHOP, new therapeutic options are required. Herein, we report the first case of extranodal DBCL of the lung with a concomitant MG who achieved a long lasting complete remission with lenalidomide.Case presentationThe 73-yea

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… In addition, a rare variant of PBL is characterized by having a translocation of ALK to the clathrin gene on chromosome 17 [ 11 ]. Even multiple myeloma (MM) with plasmobastic features present morphological similarities to DLBCL with MG. However, its immunophenotype resembles PBL [ 12 – 14 ]. …

Critical considerations for targeting colorectal liver metastases with nanotechnology.

Colorectal cancer remains a significant cause of morbidity and mortality worldwide. Half of all patients develop liver metastases, presenting unique challenges for their treatment. The shortcomings of conventional chemotherapy has encouraged the use of nanomedicines; the application of nanotechnology in the diagnosis and treatment of disease. In spite of technological improvements in nanotechnology, the complexity of biological systems hinders the prospect of nanomedicines being applied in cancer therapy at the present time. This review highlights current biological barriers and discusses aspe

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… Active uptake mechanisms govern the delivery of NPs into tumor cells and these include endocytic pathways such as clathrin‐dependent, caveolin‐dependent, macro‐pinocytosis and phagocytosis. … Additionally, NPs smaller than 200 nm were preferentially internalized by clathrin‐dependent endocytosis, while with increasing sizes beyond 200 nm, a shift towards caveolin‐dependent endocytosis was observed (Oh & Park, 2014 ; Rejman, Oberle, Zuhorn, & Hoekstra, 2004 ). …