Pharmacological Reviews最新文献

Cancer and cardiovascular disease (CVD) are the 2 biggest killers worldwide. Specific treatments have been developed for the 2 diseases. However, mutual therapeutic targets should be considered because of the overlap of cellular and molecular mechanisms. Cancer research has grown at a fast pace, leading to an increasing number of new mechanistic treatments. Some of these drugs could prove useful for treating CVD, which realizes the concept of cancer drug repurposing. This review provides a comprehensive outline of the shared hallmarks of cancer and CVD, primarily ischemic heart disease and heart failure. We focus on chronic inflammation, altered immune response, stromal and vascular cell activation, and underlying signaling pathways causing pathological tissue remodeling. There is an obvious scope for targeting those shared mechanisms, thereby achieving reciprocal preventive and therapeutic benefits. Major attention is devoted to illustrating the logic, advantages, challenges, and viable examples of drug repurposing and discussing the potential influence of sex, gender, age, and ethnicity in realizing this approach. Artificial intelligence will help to refine the personalized application of drug repurposing for patients with CVD. SIGNIFICANCE STATEMENT: Cancer and cardiovascular disease (CVD), the 2 biggest killers worldwide, share several underlying cellular and molecular mechanisms. So far, specific therapies have been developed to tackle the 2 diseases. However, the development of new cardiovascular drugs has been slow compared with cancer drugs. Understanding the intersection between pathological mechanisms of the 2 diseases provides the basis for repurposing cancer therapeutics for CVD treatment. This approach could allow the rapid development of new drugs for patients with CVDs.

The oceans are a rich source of a myriad of structurally different and unique natural products that are mainly found in invertebrates, with potential applications in different disciplines. Microbial infection and cancer are the leading causes of death worldwide. The discovery of new sources of therapy for microbial infections is an urgent requirement owing to the emergence of pathogenic microorganisms that are resistant to existing therapies. Marine bioactives have been demonstrated to be promising sources for the discovery and development of novel antimicrobial and anticancer compounds. Several marine compounds are confirmed to have antibacterial effects, and most marine-based antifungal compounds are cytotoxic. Numerous antitumor marine natural products, derived mainly from not only sponges or molluscs but also bryozoans and cyanobacteria, exhibit potent antimitotic activity. In addition, marine biodiversity offers some possible leads or new drugs to treat human immunodeficiency virus. A majority of marine-derived drugs are currently in clinical trials or under preclinical evaluation. Furthermore, marine-based drugs approved by the US Food and Drug Administration are available in the market. This review summarizes the sources, mechanisms of action, and potential utilization of marine natural products such as peptides, alkaloids, polyketides, polyphenols, terpenoids, and sterols as antifungal, antibacterial, antiviral, and anticancer compounds. SIGNIFICANCE STATEMENT: Utilization of natural bioactive compounds from marine resources is a crucial advancement in the field of health care and wellness. A valuable source of potent compounds with therapeutic potential exists in marine organisms. These bioactives offer promising medicinal value for disease prevention, promoting overall wellbeing, and advancing pharmaceutical and nutraceutical industries. Their sustainable extraction and utilization not only benefit human health but also contribute to the conservation of marine ecosystems. This transformative approach enhances global health outcomes and sustainability.

For most vertebrates, bitter perception plays a critical role in the detection of potentially harmful substances in food items. The detection of bitter compounds is facilitated by specialized receptors located in the taste buds of the oral cavity. This work focuses on these receptors, including their sensitivities, structure-function relationships, agonists, and antagonists. The existence of numerous bitter taste receptor variants in the human population and the fact that several of them profoundly affect individual perceptions of bitter tastes are discussed as well. Moreover, the identification of bitter taste receptors in numerous tissues outside the oral cavity and their multiple proposed roles in these tissues are described briefly. Although this work is mainly focused on human bitter taste receptors, it is imperative to compare human bitter taste with bitter taste of other animals to understand which forces might have shaped the evolution of bitter taste receptors and their functions and to distinguish apparently typical human features from rather general ones. For readers who are not very familiar with the gustatory system, short descriptions of taste anatomy, signal transduction, and oral bitter taste receptor expression are included in the beginning of this article. SIGNIFICANCE STATEMENT: Apart from their role as sensors for potentially harmful substances in the oral cavity, the numerous additional roles of bitter taste receptors in tissues outside the gustatory system have recently received much attention. For careful assessment of their functions inside and outside the taste system, a solid knowledge of the specific and general pharmacological features of these receptors and the growing toolbox available for studying them is imperative and provided in this work.