Statins: a repurposed drug to fight cancer Jiang, Wen; Hu, Jin-Wei; He, Xu-Ran ...
Journal of experimental & clinical cancer research,
07/2021, Letnik:
40, Številka:
1
Journal Article
Recenzirano
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As competitive HMG-CoA reductase (HMGCR) inhibitors, statins not only reduce cholesterol and improve cardiovascular risk, but also exhibit pleiotropic effects that are independent of their ...lipid-lowering effects. Among them, the anti-cancer properties of statins have attracted much attention and indicated the potential of statins as repurposed drugs for the treatment of cancer. A large number of clinical and epidemiological studies have described the anticancer properties of statins, but the evidence for anticancer effectiveness of statins is inconsistent. It may be that certain molecular subtypes of cancer are more vulnerable to statin therapy than others. Whether statins have clinical anticancer effects is still an active area of research. Statins appear to enhance the efficacy and address the shortcomings associated with conventional cancer treatments, suggesting that statins should be considered in the context of combined therapies for cancer. Here, we present a comprehensive review of the potential of statins in anti-cancer treatments. We discuss the current understanding of the mechanisms underlying the anti-cancer properties of statins and their effects on different malignancies. We also provide recommendations for the design of future well-designed clinical trials of the anti-cancer efficacy of statins.
Summary
Crop loss due to soil salinization is a global threat to agriculture. Nitric oxide (NO) and ethylene involve in multiple plant tolerance. However, their interaction in salt resistance remains ...largely elusive.
We tested the mutual induction between NO and ethylene, and then identified an 1‐aminocyclopropane‐1‐carboxylate oxidase homolog 4 (ACOh4) that influences ethylene synthesis and salt tolerance through NO‐mediated S‐nitrosylation.
Both NO and ethylene positively responded to salt stress. Furthermore, NO participated in salt‐induced ethylene production. Salt tolerance evaluation showed that function of NO was abolished by inhibiting ethylene production. Conversely, function of ethylene was little influenced by blocking NO generation. ACO was identified as the target of NO to control ethylene synthesis. In vitro and in vivo results suggested that ACOh4 was S‐nitrosylated at Cys172, resulting in its enzymatic activation. Moreover, ACOh4 was induced by NO through transcriptional manner. Knockdown of ACOh4 abolished NO‐induced ethylene production and salt tolerance. At physiological status, ACOh4 positively regulates the Na+ and H+ efflux, and keeps K+/Na+ homeostasis by promoting salt‐resistive genes' transcripts.
Our findings validate a role of NO‐ethylene module in salt tolerance and uncover a novel mechanism of how NO promoting ethylene synthesis against adversity.
Summary
Although saline–alkali stress can improve tomato quality, the detailed molecular processes that balance stress tolerance and quality are not well‐understood.
Our research links nitric oxide ...(NO) and γ‐aminobutyric acid (GABA) with the control of root malate exudation and fruit malate storage, mediated by aluminium‐activated malate transporter 9/14 (SlALMT9/14). By modifying a specific S‐nitrosylated site on pyruvate‐dependent GABA transaminase 1 (SlGABA‐TP1), we have found a way to enhance both plant's saline–alkali tolerance and fruit quality.
Under saline–alkali stress, NO levels vary in tomato roots and fruits. High NO in roots leads to S‐nitrosylation of SlGABA‐TP1/2/3 at Cys316/258/316, reducing their activity and increasing GABA. This GABA then reduces malate exudation from roots and affects saline–alkali tolerance by interacting with SlALMT14. In fruits, a moderate NO level boosts SlGABA‐TP1 expression and GABA breakdown, easing GABA's block on SlALMT9 and increasing malate storage. Mutants of SlGABA‐TP1C316S that do not undergo S‐nitrosylation maintain high activity, supporting malate movement in both roots and fruits under stress.
This study suggests targeting SlGABA‐TP1Cys316 in tomato breeding could significantly improve plant's saline–alkali tolerance and fruit quality, offering a promising strategy for agricultural development.
Accumulating evidence shows that cellular and acellular components in tumor microenvironment (TME) can reprogram tumor initiation, growth, invasion, metastasis, and response to therapies. Cancer ...research and treatment have switched from a cancer-centric model to a TME-centric one, considering the increasing significance of TME in cancer biology. Nonetheless, the clinical efficacy of therapeutic strategies targeting TME, especially the specific cells or pathways of TME, remains unsatisfactory. Classifying the chemopathological characteristics of TME and crosstalk among one another can greatly benefit further studies exploring effective treating methods. Herein, we present an updated image of TME with emphasis on hypoxic niche, immune microenvironment, metabolism microenvironment, acidic niche, innervated niche, and mechanical microenvironment. We then summarize conventional drugs including aspirin, celecoxib, β-adrenergic antagonist, metformin, and statin in new antitumor application. These drugs are considered as viable candidates for combination therapy due to their antitumor activity and extensive use in clinical practice. We also provide our outlook on directions and potential applications of TME theory. This review depicts a comprehensive and vivid landscape of TME from biology to treatment.
To discover new drugs to combat COVID-19, an understanding of the molecular basis of SARS-CoV-2 infection is urgently needed. Here, for the first time, we report the crucial role of cathepsin L ...(CTSL) in patients with COVID-19. The circulating level of CTSL was elevated after SARS-CoV-2 infection and was positively correlated with disease course and severity. Correspondingly, SARS-CoV-2 pseudovirus infection increased CTSL expression in human cells in vitro and human ACE2 transgenic mice in vivo, while CTSL overexpression, in turn, enhanced pseudovirus infection in human cells. CTSL functionally cleaved the SARS-CoV-2 spike protein and enhanced virus entry, as evidenced by CTSL overexpression and knockdown in vitro and application of CTSL inhibitor drugs in vivo. Furthermore, amantadine, a licensed anti-influenza drug, significantly inhibited CTSL activity after SARS-CoV-2 pseudovirus infection and prevented infection both in vitro and in vivo. Therefore, CTSL is a promising target for new anti-COVID-19 drug development.
To avoid large open surgery using scaffold transplants, small‐sized cell carriers are employed to repair complexly shaped tissue defects. However, most cell carriers show poor cell adherences and ...viability. Therefore, polyhydroxyalkanoate (PHA), a natural biopolymer, is used to prepare highly open porous microspheres (OPMs) of 300–360 µm in diameter, combining the advantages of microspheres and scaffolds to serve as injectable carriers harboring proliferating stem cells. In addition to the convenient injection to a defected tissue, and in contrast to poor performances of OPMs made of polylactides (PLA OPMs) and traditional less porous hollow microspheres (PHA HMs), PHA OPMs present suitable surface pores of 10–60 µm and interconnected passages with an average size of 8.8 µm, leading to a high in vitro cell adhesion of 93.4%, continuous proliferation for 10 d and improved differentiation of human bone marrow mesenchymal stem cells (hMSCs). PHA OPMs also support stronger osteoblast‐regeneration compared with traditional PHA HMs, PLA OPMs, commercial hyaluronic acid hydrogels, and carrier‐free hMSCs in an ectopic bone‐formation mouse model. PHA OPMs protect cells against stresses during injection, allowing more living cells to proliferate and migrate to damaged tissues. They function like a micro‐Noah's Ark to safely transport cells to a defect tissue.
Combining the advantages of microspheres and scaffolds, highly open porous microspheres (OPMs) made of polyhydroxyalkanoate (PHA) are developed as injectable carriers harboring growing stem cells. The PHA OPMs protect the stem cells from stresses during injection, allowing more living cells to proliferate and migrate to damaged tissues, functioning like a micro‐Noah's Ark to safely transport cells to a designated tissue location for regeneration.
After more than three decades of high growth based on its low-wage advantage and relatively favorable demographics—in combination with market-oriented reforms and openness to the world economy—China ...is at a crossroads with a much higher wage and a shrinking work force. Future growth will depend, by necessity, more on the generation of increased productivity, and domestic innovation will play an important part in this. In this paper, we assess the likelihood that China can make the necessary transition. Using data on expenditure on research and development, and patent applications, receipts, and citations, we show that the Chinese economy has become increasingly innovative. We will argue that rising wages and expanding markets are among the important drivers of China's growth in innovation. On the other hand, we find evidence of resource misallocation in the innovation area: while state-owned firms receive more subsidies, private firms exhibit more innovation results. Innovation can presumably progress even faster if resource misallocation can be tackled.
Application of computing and communications intelligence effectively improves the quality of monitoring and control of smart grids. However, the dependence on information technology also increases ...vulnerability to malicious attacks. False data injection (FDI), that attack on the integrity of data, is emerging as a severe threat to the supervisory control and data acquisition system. In this paper, we exploit deep learning techniques to recognize the behavior features of FDI attacks with the historical measurement data and employ the captured features to detect the FDI attacks in real-time. By doing so, our proposed detection mechanism effectively relaxes the assumptions on the potential attack scenarios and achieves high accuracy. Furthermore, we propose an optimization model to characterize the behavior of one type of FDI attack that compromises the limited number of state measurements of the power system for electricity theft. We illustrate the performance of the proposed strategy through the simulation by using IEEE 118-bus test system. We also evaluate the scalability of our proposed detection mechanism by using IEEE 300-bus test system.
This paper proposes an accounting framework that breaks up a country's gross exports into various value-added components by source and additional double-counted terms. Our parsimonious framework ...bridges a gap between official trade statistics (in gross value terms) and national accounts (in value-added terms), and integrates all previous measures of vertical specialization and value-added trade in the literature into a unified framework. To illustrate the potential of such a method, we present a number of applications including re-computing revealed comparative advantages and the magnifying impact of multi-stage production on trade costs.
Nanotechnology has become more and more potentially used in diagnosis or treatment of diseases. Advances in nanotechnology have led to new and improved nanomaterials in biomedical applications. ...Common nanomaterials applicable in biomedical applications include liposomes, polymeric micelles, graphene, carbon nanotubes, quantum dots, ferroferric oxide nanoparticles, gold nanoparticles (Au NPs), and so on. Among them, Au NPs have been considered as the most interesting nanomaterial because of its unique optical, electronic, sensing and biochemical properties. Au NPs have been potentially applied for medical imaging, drug delivery, and tumor therapy in the early detection, diagnosis, and treatment of diseases. This review focuses on some recent advances in the use of Au NPs as drug carriers for the intracellular delivery of therapeutics and as molecular nanoprobes for the detection and monitoring of target molecules.
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