Multiple Myeloma Inhibitory Activity of Plant Natural Products

A literature search on plant natural products with antimyeloma activity until the end of 2020 resulted in 92 compounds with effects on at least one human myeloma cell line. Compounds were divided in different compound classes and both their structure-activity-relationships as well as eventual correlations with the pathways described for Multiple Myeloma were discussed. Each of the major compound classes in this review (alkaloids, phenolics, terpenes) revealed interesting candidates, such as dioncophyllines, a group of naphtylisoquinoline alkaloids, which showed pronounced and selective induction of apoptosis when substituted in position 7 of the isoquinoline moiety. Interestingly, out of the phenolic compound class, two of the most noteworthy constituents belong to the relatively small subclass of xanthones, rendering this group a good starting point for possible further drug development. The class of terpenoids also provides noteworthy constituents, such as the highly oxygenated diterpenoid oridonin, which exhibited antiproliferative effects equal to those of bortezomib on RPMI8226 cells. Moreover, triterpenoids containing a lactone ring and/or quinone-like substructures, e.g., bruceantin, whitaferin A, withanolide F, celastrol, and pristimerin, displayed remarkable activity, with the latter two compounds acting as inhibitors of both NF-κB and proteasome chymotrypsin-like activity

Role of Natural Bioactive Compounds in the Rise and Fall of Cancers

Recent years have seen the idea of a close association between nutrition and the modulation of cancer development/progression reinforced. An increasing amount of experimental and epidemiological evidence has been produced supporting the concept that many different bioactive components of food (e.g. polyphenols, mono- and polyunsaturated fatty acids, methyl-group donors, etc.) may be implicated in either the promotion of or the protection against carcinogenesis. At the cellular level, such compounds can have an impact on different but sometimes intertwined processes, such as growth and differentiation, DNA repair, programmed cell death, and oxidative stress. In addition, compelling evidence is starting to build up of the existence of primary epigenetic targets of dietary compounds, such as oncogenic/oncosuppressor miRNAs or DNA-modifying enzymes, which in turn impair gene expression and function. Since there is a growing interest in the study of the biochemical and molecular role played by food components and its impact on cellular processes and/or gene expressions directed towards the fine-tuning of cancer phenotypes, in this Special Issue researchers contributed with either research or review articles presenting the latest findings on the intracellular pathways and mechanisms affected by natural bioactive dietary molecules

In sickness and in health : The functional role of extracellular vesicles in physiology and pathology in vivo Part II: Pathology

It is clear from Part I of this series that extracellular vesicles (EVs) play a critical role in maintaining the homeostasis of most, if not all, normal physiological systems. However, the majority of our knowledge about EV signalling has come from studying them in disease. Indeed, EVs have consistently been associated with propagating disease pathophysiology. The analysis of EVs in biofluids, obtained in the clinic, has been an essential of the work to improve our understanding of their role in disease. However, to interfere with EV signalling for therapeutic gain, a more fundamental understanding of the mechanisms by which they contribute to pathogenic processes is required. Only by discovering how the EV populations in different biofluids change-size, number, and physicochemical composition-in clinical samples, may we then begin to unravel their functional roles in translational models in vitro and in vivo, which can then feedback to the clinic. In Part II of this review series, the functional role of EVs in pathology and disease will be discussed, with a focus on in vivo evidence and their potential to be used as both biomarkers and points of therapeutic intervention.Peer reviewe

Epitranscriptomic regulation in breast cancer and PCB-induced liver disease.

Post-transcriptional RNA modifications including N6-methyladenosine (m6A) regulate mRNA stability, splicing, and translation. My research examined m6A in two disease models: breast cancer (BCa) and non-alcoholic fatty liver disease (NAFLD). Acquired resistance to endocrine therapies (ET) develops in approximately 20% of BCa patients with estrogen receptor α positive (ER+) tumors following treatment. The mechanisms by which tumor cells evade ET are not completely understood. Using a cell line model, we investigated the role of an m6A reader protein, HNRNPA2B1 (A2B1) that is upregulated in ET-resistant ER+ BCa cells. Stable overexpression of A2B1 in ET-sensitive MCF-7 cells (MCF-7-A2B1), results in ET resistance, whereas knockdown of A2B1 in ET-resistant cells restored ET-sensitivity. microRNAs (miRNAs) downregulated by transient overexpression of A2B1 were identified to target two key enzymes (PSAT1 and PHGDH) in the serine biosynthetic pathway (SSP) which is upregulated in ET-resistant BCa cells and in tumors from patients with ET-resistant disease. Using luciferase assays, PSAT1 and PHGDH were validated as bona fide targets of miRNAs downregulated by A2B1 (miR-145-5p and miR-424-5p targeting PSAT1, miR-34b-5p and miR-876-5p targeting PHGDH). Exogenous overexpression of the validated miRNAs decreased endogenous PSAT1 and PHGDH in ET-resistant BCa cells, resulting in increased sensitivity to ET in vitro. In the second model, alterations in the m6A epitranscriptome were identified in the livers of male C57Bl/6Jmice after a single, oral exposure to polychlorinated biphenyls (PCB), a class of persistent organic pollutants, in combination with 12 weeks on a high fat diet (HFD). Our results demonstrated that exposure to PCBs in combination with a HFD resulted in major changes to the mRNA and miRNA transcriptomes, and m6A epitranscriptome. Pathway analysis of the genes in which m6A peaks were altered identified pathways involved in the progression from steatosis to steatohepatitis in NAFLD. PCB exposures also resulted in changes to alternative splicing (AS) mechanisms and events, suggesting that PCB-induced m6A changes contribute to altered isoforms expression in NAFLD. Taken together, the results in this dissertation demonstrate the significant role of altered m6A in two common human diseases

In sickness and in health : The functional role of extracellular vesicles in physiology and pathology in vivo Part II: Pathology

It is clear from Part I of this series that extracellular vesicles (EVs) play a critical role in maintaining the homeostasis of most, if not all, normal physiological systems. However, the majority of our knowledge about EV signalling has come from studying them in disease. Indeed, EVs have consistently been associated with propagating disease pathophysiology. The analysis of EVs in biofluids, obtained in the clinic, has been an essential of the work to improve our understanding of their role in disease. However, to interfere with EV signalling for therapeutic gain, a more fundamental understanding of the mechanisms by which they contribute to pathogenic processes is required. Only by discovering how the EV populations in different biofluids change-size, number, and physicochemical composition-in clinical samples, may we then begin to unravel their functional roles in translational models in vitro and in vivo, which can then feedback to the clinic. In Part II of this review series, the functional role of EVs in pathology and disease will be discussed, with a focus on in vivo evidence and their potential to be used as both biomarkers and points of therapeutic intervention.Peer reviewe

Literature-based discovery of known and potential new mechanisms for relating the status of cholesterol to the progression of breast cancer

Breast cancer has been studied for a long period of time and from a variety of perspectives in order to understand its pathogeny. The pathogeny of breast cancer can be classified into two groups: hereditary and spontaneous. Although cancer in general is considered a genetic disease, spontaneous factors are responsible for most of the pathogeny of breast cancer. In other words, breast cancer is more likely to be caused and deteriorated by the dysfunction of a physical molecule than be caused by germline mutation directly. Interestingly, cholesterol, as one of those molecules, has been discovered to correlate with breast cancer risk. However, the mechanisms of how cholesterol helps breast cancer progression are not thoroughly understood. As a result, this study aims to study known and discover potential new mechanisms regarding to the correlation of cholesterol and breast cancer progression using literature review and literature-based discovery. The known mechanisms are further classified into four groups: cholesterol membrane content, transport of cholesterol, cholesterol metabolites, and other. The potential mechanisms, which are intended to provide potential new treatments, have been identified and checked for feasibility by an expert

Oncogene and Cancer

This book describes a course of cancer growth starting from normal cells to cancerous form and the genomic instability, the cancer treatment as well as its prevention in form of the invention of a vaccine. Some diseases are also discussed in detail, such as breast cancer, leucaemia, cervical cancer, and glioma. Understanding cancer through its molecular mechanism is needed to reduce the cancer incidence. How to treat cancer more effectively and the problems like drug resistance and metastasis are very clearly illustrated in this publication as well as some research result that could be used to treat the cancer patients in the very near future. The book was divided into six main sections: 1. HER2 Carcinogenesis: Etiology, Treatment and Prevention; 2. DNA Repair Mechanism and Cancer; 3. New Approach to Cancer Mechanism; 4. New Role of Oncogenes and Tumor Suppressor Genes; 5. Non Coding RNA and Micro RNA in Tumorigenesis; 6. Oncogenes for Transcription Factor

In sickness and in health: The functional role of extracellular vesicles in physiology and pathology in vivo. Part 2

It is clear from Part I of this series that extracellular vesicles (EVs) play a critical role in maintaining the homeostasis of most, if not all, normal physiological systems. However, the majority of our knowledge about EV signalling has come from studying them in disease. Indeed, EVs have consistently been associated with propagating disease pathophysiology. The analysis of EVs in biofluids, obtained in the clinic, has been an essential of the work to improve our understanding of their role in disease. However, to interfere with EV signalling for therapeutic gain, a more fundamental understanding of the mechanisms by which they contribute to pathogenic processes is required. Only by discovering how the EV populations in different biofluids change—size, number, and physicochemical composition—in clinical samples, may we then begin to unravel their functional roles in translational models in vitro and in vivo, which can then feedback to the clinic. In Part II of this review series, the functional role of EVs in pathology and disease will be discussed, with a focus on in vivo evidence and their potential to be used as both biomarkers and points of therapeutic intervention

Biological and Pharmacological Activity of Plant Natural Compounds

Phytotherapy is probably the oldest form of medicine; however, it represents a new therapeutic tool for healthcare workers. Indeed plants are an infinite source of novel molecules, with countless possible combinations. This collection of articles (a Special Issue from Molecules) brings together the most up-to-date studies on the use of plant-derived compounds, ranging from their anti-inflammatory, antioxidant, and anticancer effects to the revision of the prominent literature