RESUMO
Information about the impact of interactions between amyloid proteins on their fibrillization propensity is scattered among many experimental articles and presented in unstructured form. We manually curated information located in almost 200 publications (selected out of 562 initially considered), obtaining details of 883 experimentally studied interactions between 46 amyloid proteins or peptides. We also proposed a novel standardized terminology for the description of amyloid-amyloid interactions, which is included in our database, covering all currently known types of such a cross-talk, including inhibition of fibrillization, cross-seeding and other phenomena. The new approach allows for more specific studies on amyloids and their interactions, by providing very well-defined data. AmyloGraph, an online database presenting information on amyloid-amyloid interactions, is available at (http://AmyloGraph.com/). Its functionalities are also accessible as the R package (https://github.com/KotulskaLab/AmyloGraph). AmyloGraph is the only publicly available repository for experimentally determined amyloid-amyloid interactions.
Assuntos
Amiloide , Proteínas Amiloidogênicas , Proteínas Amiloidogênicas/metabolismo , Peptídeos , Bases de Dados de ProteínasRESUMO
Cancer diseases constitute a major health problem which leads to the death of millions of people annually. They are unique among other diseases because cancer cells can perfectly adapt to the environment that they create themselves. This environment is usually highly hostile and for normal cells it would be hugely difficult to survive, however neoplastic cells not only can survive but also manage to proliferate. One of the reasons is that they can alter immunological pathways which allow them to be flexible and change their phenotype to the one needed in specific conditions. The aim of this paper is to describe some of these immunological pathways that play significant roles in gynecologic neoplasms as well as review recent research in this field. It is of high importance to possess extensive knowledge about these processes, as greater understanding leads to creating more specialized therapies which may prove highly effective in the future.
Assuntos
Neoplasias da Mama , Neoplasias dos Genitais Femininos , Humanos , Feminino , Neoplasias dos Genitais Femininos/imunologia , Neoplasias dos Genitais Femininos/patologia , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Microambiente Tumoral/imunologia , AnimaisRESUMO
Researchers are amazed at the multitude of biological effects of 3',4',5,7-tetrahydroxyflavone, more commonly known as luteolin, as it simultaneously has antioxidant and pro-oxidant, as well as antimicrobial, anti-inflammatory, and cancer-preventive, properties. The anticancer properties of luteolin constitute a mosaic of pathways due to which this flavonoid influences cancer cells. Not only is it able to induce apoptosis and inhibit cancer cell proliferation, but it also suppresses angiogenesis and metastasis. Moreover, luteolin succeeds in cancer cell sensitization to therapeutically induced cytotoxicity. Nevertheless, apart from its promising role in chemoprevention, luteolin exhibits numerous potential utilizations in patients with conditions other than neoplasms, which include inflammatory skin diseases, diabetes mellitus, and COVID-19. This review aims to present the multidimensionality of the luteolin's impact on both neoplastic and nonneoplastic diseases. When it comes to neoplasms, we intend to describe the complexity of the molecular mechanisms that underlay luteolin's anticancer effectiveness, as well as to prove the usefulness of integrating this flavonoid in cancer therapy via the analysis of recent research on breast, colon, and lung cancer. Regarding nonneoplastic diseases, this review aims to emphasize the importance of researching the potential of luteolin in areas such as diabetology, virology, and dermatology as it summarizes the most important discoveries in those fields regarding its application.
Assuntos
Neoplasias Pulmonares , Neoplasias , Humanos , Luteolina/farmacologia , Luteolina/uso terapêutico , Neoplasias/metabolismo , Antioxidantes/farmacologia , Quimioprevenção , ApoptoseRESUMO
Crohn's disease (CD) is a chronic inflammatory disease that most frequently affects part of the distal ileum, but it may affect any part of the gastrointestinal tract. CD may also be related to systemic inflammation and extraintestinal manifestations. Alzheimer's disease (AD) is the most common neurodegenerative disease, gradually worsening behavioral and cognitive functions. Despite the meaningful progress, both diseases are still incurable and have a not fully explained, heterogeneous pathomechanism that includes immunological, microbiological, genetic, and environmental factors. Recently, emerging evidence indicates that chronic inflammatory condition corresponds to an increased risk of neurodegenerative diseases, and intestinal inflammation, including CD, increases the risk of AD. Even though it is now known that CD increases the risk of AD, the exact pathways connecting these two seemingly unrelated diseases remain still unclear. One of the key postulates is the gut-brain axis. There is increasing evidence that the gut microbiota with its proteins, DNA, and metabolites influence several processes related to the etiology of AD, including ß-amyloid abnormality, Tau phosphorylation, and neuroinflammation. Considering the role of microbiota in both CD and AD pathology, in this review, we want to shed light on bacterial amyloids and their potential to influence cerebral amyloid aggregation and neuroinflammation and provide an overview of the current literature on amyloids as a potential linker between AD and CD.
Assuntos
Doença de Alzheimer , Doença de Crohn , Microbioma Gastrointestinal , Doença de Alzheimer/metabolismo , Doença de Alzheimer/etiologia , Doença de Crohn/metabolismo , Doença de Crohn/microbiologia , Humanos , Peptídeos beta-Amiloides/metabolismo , Amiloide/metabolismo , Animais , Eixo Encéfalo-Intestino/fisiologia , Encéfalo/patologia , Encéfalo/metabolismo , Inflamação/metabolismoRESUMO
Naringenin is a trihydroxyflavanone present in large amount in different citrus fruits, e.g., oranges, pomelos, grapefruits, but also in tomatoes, fenugreek and coffee. It has a wide range of pharmacological and biological effects beneficial to human health. Its antioxidant, anti-cancer, anti-inflammatory, antifungal and antimicrobial activity is frequently reported in scientific literature. In this review we presented the current state of knowledge on the antimicrobial activity of naringenin and its natural and synthetic derivatives as a phytobiotic against resistant Gram-positive and Gram-negative bacteria as well as fungi in humans. Most of the data reported here have been obtained from in vitro or in vivo studies. Over the past few years, due to the overuse of antibiotics, the occurrence of bacteria resistant to all available antibiotics has been growing. Therefore, the main focus here is on antibiotic resistant strains, which are a significant, worldwide problem in the treatment of infectious diseases. The situation is so alarming that the WHO has listed microbial resistance to drugs on the list of the 10 most important health problems facing humanity. In addition, based on scientific reports from recent years, we described the potential molecular mechanism of action of these bioflavonoids against pathogenic strains of microorganisms. As plant-derived substances have been pushed out of use with the beginning of the antibiotic era, we hope that this review will contribute to their return as alternative methods of preventing and treating infections in the epoch of drug resistance.
RESUMO
CD38 is a myeloid antigen present both on the cell membrane and in the intracellular compartment of the cell. Its occurrence is often enhanced in cancer cells, thus making it a potential target in anticancer therapy. Daratumumab and isatuximab already received FDA approval, and novel agents such as MOR202, TAK079 and TNB-738 undergo clinical trials. Also, novel therapeutics such as SAR442085 aim to outrank the older antibodies against CD38. Multiple myeloma and immunoglobulin light-chain amyloidosis may be effectively treated with anti-CD38 immunotherapy. Its role in other hematological malignancies is also important concerning both diagnostic process and potential treatment in the future. Aside from the hematological malignancies, CD38 remains a potential target in gastrointestinal, neurological and pulmonary system disorders. Due to the strong interaction of CD38 with TCR and CD16 on T cells, it may also serve as the biomarker in transplant rejection in renal transplant patients. Besides, CD38 finds its role outside oncology in systemic lupus erythematosus and collagen-induced arthritis. CD38 plays an important role in viral infections, including AIDS and COVID-19. Most of the undergoing clinical trials focus on the use of anti-CD38 antibodies in the therapy of multiple myeloma, CD19- B-cell malignancies, and NK cell lymphomas. This review focuses on targeting CD38 in cancer and non-cancerous diseases using antibodies, cell-based therapies and CD38 inhibitors. We also provide a summary of current clinical trials targeting CD38.