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.
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.
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.
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