Search

Given the profound multiple myeloma (MM) heterogeneity in clonal proliferation of malignant plasma cells (PCs) and anti-MM therapeutic potential of nanotherapies, it is inevitable to develop treatment plan for patients with MM. Two composite nanoparticles (NPs), As 4 S 4 /Fe 3 O 4 (4:1) and As 4 S 4 /Fe 3 O 4 (1:1) demonstrated effective anti-MM activity in in vitro, ex vivo, and in vivo in xenograft mouse model. Composite NPs triggered activation of p-ERK1/2/p-JNK, and downregulation of c-Myc, p-PI3K, p-4E-BP1; G 2 /M cell cycle arrest with increase in cyclin B1, histones H2AX/H3, activation of p-ATR, p-Chk1/p-Chk2, p-H2AX/p-H3; and caspase- and mitochondria-dependent apoptosis induction. NPs attenuated the stem cell-like side population in MM cells, both alone and in the presence of stroma. For a higher clinical response rate, As 4 S 4 /Fe 3 O 4 (4:1) observed synergism with dexamethasone and melphalan, while As 4 S 4 /Fe 3 O 4 (1:1) showed synergistic effects in combination with bortezomib, lenalidomide and pomalidomide anti-MM agents, providing the framework for further clinical evaluation of composite NPs in MM., Competing Interests: Declaration of competing interest The authors declare the following competing interests: K.C.A. declares advisory role (Pfizer, Amgen, Astrazeneca, Janssen, Precision Biosciences), board membership (C4 Therapeutics, Raqia, NextRNA, Window, Mana, Starton) and ownership interests (C4 Therapeutics, Oncopep, NextRNA, Raqia). Other authors declare no competing financial interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Heat shock proteins (HSPs) represent cellular chaperones that are classified into several families, including HSP27, HSP40, HSP60, HSP70, and HSP90. The role of HSPs in the cell includes the facilitation of protein folding and maintaining protein structure. Both processes play crucial roles during stress conditions in the cell such as heat shock, degradation, and hypoxia. Moreover, HSPs are important modulators of cellular proliferation and differentiation, and are strongly associated with the molecular orchestration of carcinogenesis. The expression and/or activity of HSPs in cancer cells is generally abnormally high and is associated with increased metastatic potential and activity of cancer stem cells, more pronounced angiogenesis, downregulated apoptosis, and the resistance to anticancer therapy in many patients. Based on the mentioned reasons, HSPs have strong potential as valid diagnostic, prognostic, and therapeutic biomarkers in clinical oncology. In addition, numerous papers describe the role of HSPs as chaperones in the regulation of immune responses inside and outside the cell. Importantly, highly expressed/activated HSPs may be inhibited via immunotherapeutic targets in various types of cancers. The aim of this work is to provide a comprehensive overview of the relationship between HSPs and the tumor cell with the intention of highlighting the potential use of HSPs in personalized cancer management., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

Hypertensive disorders in pregnancy represent severe complications of pregnancy, which, if not treated, can result in serious health consequences for the mother and the child. Flavonoids are bioactive secondary metabolites commonly found in fruits, vegetables, green tea, whole grains, and medicinal plants. Flavonoids exert potent protective efficacy in experimental models of hypertensive disorders in pregnancy, especially preeclampsia, demonstrated through their capacity to modulate inflammatory responses, oxidative stress, and vascular dysfunction. In addition to their potential as therapeutics, flavonoids or flavonoid-rich food could be helpful to decrease the risk of hypertensive disorders in pregnancy when included in the diet pattern before and during pregnancy. However, the clinical evaluation of the potential capacity of flavonoids in hypertensive disorders in pregnancy is insufficient. Due to promising results from experimental studies, we highlight the need for the evaluation of flavonoids also in an appropriate clinical setting, which can be, together with proper preventive strategies, helpful in the overall management of hypertensive disorders in pregnancy., (Copyright © 2022. Published by Elsevier B.V.)