Iron is an essential element that is indispensable for life. The delicate physiological body iron balance is maintained by both systemic and cellular regulatory mechanisms. The iron-regulatory hormone hepcidin assures maintenance of adequate systemic iron levels and is regulated by circulating and stored iron levels, inflammation and erythropoiesis. The kidney has an important role in preventing iron loss from the body by means of reabsorption. Cellular iron levels are dependent on iron import, storage, utilization and export, which are mainly regulated by the iron response element-iron regulatory protein (IRE-IRP) system. In the kidney, iron transport mechanisms independent of the IRE-IRP system have been identified, suggesting additional mechanisms for iron handling in this organ. Yet, knowledge gaps on renal iron handling remain in terms of redundancy in transport mechanisms, the roles of the different tubular segments and related regulatory processes. Disturbances in cellular and systemic iron balance are recognized as causes and consequences of kidney injury. Consequently, iron metabolism has become a focus for novel therapeutic interventions for acute kidney injury and chronic kidney disease, which has fuelled interest in the molecular mechanisms of renal iron handling and renal injury, as well as the complex dynamics between systemic and local cellular iron regulation.

The multifaceted role of iron in renal health and disease.

Over the last two decades, a novel subgroup of serine proteases, the cell surface-anchored serine proteases, has emerged as an important component of the human degradome, and several members have garnered significant attention for their roles in cancer progression and metastasis. A large body of literature describes that cell surface-anchored serine proteases are deregulated in cancer and that they contribute to both tumor formation and metastasis through diverse molecular mechanisms. The loss of precise regulation of cell surface-anchored serine protease expression and/or catalytic activity may be contributing to the etiology of several cancer types. There is therefore a strong impetus to understand the events that lead to deregulation at the gene and protein levels, how these precipitate in various stages of tumorigenesis, and whether targeting of selected proteases can lead to novel cancer intervention strategies. This review summarizes current knowledge about cell surface-anchored serine proteases and their role in cancer based on biochemical characterization, cell culture-based studies, expression studies, and in vivo experiments. Efforts to develop inhibitors to target cell surface-anchored serine proteases in cancer therapy will also be summarized.

Cell surface–anchored serine proteases in cancer progression and metastasis

The development of refractory tumor cells limits therapeutic efficacy in cancer by activating mechanisms that promote cellular proliferation, migration, invasion, metastasis, and survival. Benzimidazole anthelmintics have broad-spectrum action to remove parasites both in human and veterinary medicine. In addition to being antiparasitic agents, benzimidazole anthelmintics are known to exert anticancer activities, such as the disruption of microtubule polymerization, the induction of apoptosis, cell cycle (G2/M) arrest, anti-angiogenesis, and blockage of glucose transport. These antitumorigenic effects even extend to cancer cells resistant to approved therapies and when in combination with conventional therapeutics, enhance anticancer efficacy and hold promise as adjuvants. Above all, these anthelmintics may offer a broad, safe spectrum to treat cancer, as demonstrated by their long history of use as antiparasitic agents. The present review summarizes central literature regarding the anticancer effects of benzimidazole anthelmintics, including albendazole, parbendazole, fenbendazole, mebendazole, oxibendazole, oxfendazole, ricobendazole, and flubendazole in cancer cell lines, animal tumor models, and clinical trials. This review provides valuable information on how to improve the quality of life in patients with cancers by increasing the treatment options and decreasing side effects from conventional therapy.

/pdf/the-antitumor-potentials-of-benzimidazole-anthelmintics-as-45o7ihyyjj.pdf

The Antitumor Potentials of Benzimidazole Anthelmintics as Repurposing Drugs.

Proteases are a diverse group of hydrolytic enzymes, ranging from single-domain catalytic molecules to sophisticated multi-functional macromolecules. Human proteases are divided into five mechanistic classes: aspartate, cysteine, metallo, serine and threonine proteases, based on the catalytic mechanism of hydrolysis. As a protective mechanism against uncontrolled proteolysis, proteases are often produced and secreted as inactive precursors, called zymogens, containing inhibitory N-terminal propeptides. Protease propeptide structures vary considerably in length, ranging from dipeptides and propeptides of about 10 amino acids to complex multifunctional prodomains with hundreds of residues. Interestingly, sequence analysis of the different protease domains has demonstrated that propeptide sequences present higher heterogeneity compared with their catalytic domains. Therefore, we suggest that protease inhibition targeting propeptides might be more specific and have less off-target effects than classical inhibitors. The roles of propeptides, besides keeping protease latency, include correct folding of proteases, compartmentalization, liganding, and functional modulation. Changes in the propeptide sequence, thus, have a tremendous impact on the cognate enzymes. Small modifications of the propeptide sequences modulate the activity of the enzymes, which may be useful as a therapeutic strategy. This review provides an overview of known human proteases, with a focus on the role of their propeptides. We review propeptide functions, activation mechanisms, and possible therapeutic applications.

Protease propeptide structures, mechanisms of activation, and functions.

We studied the factors affecting the selectivity of peptidomimetic inhibitors of the highly homologous proteases matriptase and matriptase-2 across subpockets using docking simulations. We observed that the farther away a subpocket is located from the catalytic site, the more pronounced its role in selectivity. As a result of our exhaustive virtual screening, we biochemically validated novel potent and selective inhibitors of both enzymes.

Analysis of Subpocket Selectivity and Identification of Potent Selective Inhibitors for Matriptase and Matriptase-2

Multiple studies have indicated that albendazole (ABZ) can disrupt the microtubule in worms and have anti-tumor potential in a variety of tumors. However, the therapeutic effect of ABZ on triple-negative breast cancer (TNBC) is largely unknown, and the therapeutic evaluation of ABZ by 18F-FDG PET imaging remains relatively unexplored. The effects of ABZ on TNBC cell lines (MDA-MB-231 cells) were investigated in vitro using MTT, wound-healing, transwell migration, flow cytometry and Western blotting analyses. In vivo treatment was conducted in an MDA-MB-231 tumor-bearing nude mouse model. Mouse body weight loss was also evaluated. PET imaging was performed before and after 3 days of treatment. Tumor tissues were harvested for immunofluorescence analysis. ABZ treatment inhibited the proliferation and migration and triggered the apoptosis in MDA-MB-231 cells. Furthermore, Western blotting analysis showed that ABZ induced the apoptosis in MDA-MB-231 cells via GLUT1/AMPK/P53 signaling pathway. Long-term treatment studies found that the tumor volume of the treatment group was smaller compared with the control group, and the survival time was prolonged. In vivo 18F-FDG PET imaging showed that 3-day ABZ treatment reduced standardized uptake value (SUV) values in MDA-MB-231 xenografts compared with the controls, and immunofluorescence analysis showed more TUNEL-positive cells in the ABZ-treated mice. Our study suggested that ABZ induced the apoptosis of MDA-MB-231 cells by inhibiting glucose uptake, and it could be considered as a potential drug for TNBC cells. Moreover, 18F-FDG PET imaging could be used to monitor the early anti-tumor effect of ABZ on MDA-MB-231 tumors.

18F-FDG PET imaging for monitoring the early anti-tumor effect of albendazole on triple-negative breast cancer.

Platelet autoantibody detection is critical for immune thrombocytopenia (ITP) diagnosis and prognosis. Therefore, we aimed to establish a quantitative flow cytometric immunobead assay (FCIA) for ITP platelet autoantibodies evaluation. Capture microbeads coupled with anti-GPIX, -GPIb, -GPIIb, -GPIIIa and P-selectin antibodies were used to bind the platelet-bound autoantibodies complex generated from plasma samples of 250 ITP patients, 163 non-ITP patients and 243 healthy controls, a fluorescein isothiocyanate (FITC)-conjugated secondary antibody was the detector reagent and mean fluorescence intensity (MFI) signals were recorded by flow cytometry. Intra- and inter-assay variations of the quantitative FCIA assay were assessed. Comparisons of the specificity, sensitivity and accuracy between quantitative and qualitative FCIA or monoclonal antibody immobilization of platelet antigen (MAIPA) assay were performed. Finally, treatment process was monitored by our quantitative FCIA in 8 newly diagnosed ITPs. The coefficient of variations (CV) of the quantitative FCIA assay were respectively 9.4, 3.8, 5.4, 5.1 and 5.8% for anti-GPIX, -GPIb, -GPIIIa, -GPIIb and -P-selectin autoantibodies. Elevated levels of autoantibodies against platelet glycoproteins GPIX, GPIb, GPIIIa, GPIIb and P-selectin were detected by our quantitative FCIA in ITP patients compared to non-ITP patients or healthy controls. The sensitivity, specificity and accuracy of our quantitative assay were respectively 73.13, 81.98 and 78.65% when combining all 5 autoantibodies, while the sensitivity, specificity and accuracy of MAIPA assay were respectively 41.46, 90.41 and 72.81%. A quantitative FCIA assay was established. Reduced levels of platelet autoantibodies could be confirmed by our quantitative FCIA in ITP patients after corticosteroid treatment. Our quantitative assay is not only good for ITP diagnosis but also for ITP treatment monitoring.

/pdf/flow-cytometric-immunobead-assay-for-quantitative-detection-1m9zeqwjot.pdf

Flow cytometric immunobead assay for quantitative detection of platelet autoantibodies in immune thrombocytopenia patients.

The present invention aims to provide a high-flux fluorescent McAb nanometer microsphere kit which can rapidly, easily and accurately detect platelet antoantibodies so as to make an early diagnosis of autoimmunity diseases, comprising a, a first fluorescent nanometer microsphere solution blocked by the bovine serum albumin and connected with the monoclonal antibody SZ-1; b, a second fluorescent nanometer microsphere solution blocked by the bovine serum albumin and connected with the monoclonal antibody SZ-2; c, a third fluorescent nanometer microsphere solution blocked by the bovine serum albumin and connected with the monoclonal antibody SZ-21; d, a fourth fluorescent nanometer microsphere solution blocked by the bovine serum albumin and connected with the monoclonal antibody SZ-22; e, a fifth fluorescent nanometer microsphere solution blocked by the bovine serum albumin and connected with the monoclonal antibody SZ-51; f, fluorescein isothiocyanate connected goat anti-human polyclonal antibodies; g, a PBS liquid. The invention also provides an application of the kit and a preparation method of main components of the kit.

High-flux fluorescent McAb nanometer microsphere kit

The invention relates to the technical fields of molecular biology and immunology and especially relates to a vascular endothelial cadherin epitope, an antibody and an application thereof. The invention provides the vascular endothelial cadherin epitope, the antibody and the application thereof, wherein the amino acid sequence of the epitope is represented as the SEQ ID No.1. The epitope is located at the N-terminal of a CDH5 protein and has higher conservatism. The epitope belongs to a neutralizing epitope and can specifically recognize tumor blood vessels and inhibit generation thereof. A test proves that the epitope can specially recognize the vascular endothelial cadherin in the tumor blood vessels, thereby inhibiting the generation of the tumor blood vessels.

Vascular endothelial cadherin epitope, antibody and application thereof

N-Glycosylation Is Required for Matriptase-2 Autoactivation and Ectodomain Shedding

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Yang He

Author Tools

Chat about Author