scholarly journals Hypoxia- and MicroRNA-Induced Metabolic Reprogramming of Tumor-Initiating Cells

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 528 ◽  
Author(s):  
Pit Ullmann ◽  
Martin Nurmik ◽  
Rubens Begaj ◽  
Serge Haan ◽  
Elisabeth Letellier

Colorectal cancer (CRC), the second most common cause of cancer mortality in the Western world, is a highly heterogeneous disease that is driven by a rare subpopulation of tumorigenic cells, known as cancer stem cells (CSCs) or tumor-initiating cells (TICs). Over the past few years, a plethora of different approaches, aimed at identifying and eradicating these self-renewing TICs, have been described. A focus on the metabolic and bioenergetic differences between TICs and less aggressive differentiated cancer cells has thereby emerged as a promising strategy to specifically target the tumorigenic cell compartment. Extrinsic factors, such as nutrient availability or tumor hypoxia, are known to influence the metabolic state of TICs. In this review, we aim to summarize the current knowledge on environmental stress factors and how they affect the metabolism of TICs, with a special focus on microRNA (miRNA)- and hypoxia-induced effects on colon TICs.

2018 ◽  
Author(s):  
Clive Smith ◽  
Meghan Hudson ◽  
Victoria Turner Turner ◽  
Craig Border ◽  
Allen Thompson

UNSTRUCTURED Pancreatic carcinoma is being recognized to be responsible for an increasing number of cancer-related deaths, especially in the western world. A deluge of risk factors have been described in the literature. Some of the important ones include smoking, alcohol and metabolic diseases like obesity. It also poses challenges in diagnosis and treatment despite recent advances in diagnostic, surgical and other therapeutic advancements. This is a narrative review of the findings of multiple studies that were retrieved from electronic databases like PubMed, Google Scholar, Scopus, Medline, Embase, and Cochrane databases. We summarize the current knowledge regarding the epidemiology and various risk factors for the development of pancreatic carcinoma.


2017 ◽  
Vol 2017 ◽  
pp. 1-17 ◽  
Author(s):  
Marco Ragusa ◽  
Cristina Barbagallo ◽  
Duilia Brex ◽  
Angela Caponnetto ◽  
Matilde Cirnigliaro ◽  
...  

Over the past few years, noncoding RNAs (ncRNAs) have been extensively studied because of the significant biological roles that they play in regulation of cellular mechanisms. ncRNAs are associated to higher eukaryotes complexity; accordingly, their dysfunction results in pathological phenotypes, including cancer. To date, most research efforts have been mainly focused on how ncRNAs could modulate the expression of protein-coding genes in pathological phenotypes. However, recent evidence has shown the existence of an unexpected interplay among ncRNAs that strongly influences cancer development and progression. ncRNAs can interact with and regulate each other through various molecular mechanisms generating a complex network including different species of RNAs (e.g., mRNAs, miRNAs, lncRNAs, and circRNAs). Such a hidden network of RNA-RNA competitive interactions pervades and modulates the physiological functioning of canonical protein-coding pathways involved in proliferation, differentiation, and metastasis in cancer. Moreover, the pivotal role of ncRNAs as keystones of network structural integrity makes them very attractive and promising targets for innovative RNA-based therapeutics. In this review we will discuss: (1) the current knowledge on complex crosstalk among ncRNAs, with a special focus on cancer; and (2) the main issues and criticisms concerning ncRNAs targeting in therapeutics.


2019 ◽  
Author(s):  
Zhang Lee ◽  
Zengjian Wang ◽  
Johannes Lang ◽  
Sun Xinyu ◽  
Yao-Ting Sung

Pancreatic carcinoma is being recognized to be responsible for an increasing number of cancer-related deaths, especially in the western world. A deluge of risk factors have been described in the literature. Some of the important ones include smoking, alcohol and metabolic diseases like obesity. It also poses challenges in diagnosis and treatment despite recent advances in diagnostic, surgical and other therapeutic advancements. This is a narrative review of the findings of multiple studies that were retrieved from electronic databases like PubMed, Google Scholar, Scopus, Medline, Embase, and Cochrane databases. We summarize the current knowledge regarding the epidemiology and various risk factors for the development of pancreatic carcinoma.


Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 724
Author(s):  
Nathalie Acevedo ◽  
Bilal Alashkar Alhamwe ◽  
Luis Caraballo ◽  
Mei Ding ◽  
Antonio Ferrante ◽  
...  

Epidemiological studies have shown a dramatic increase in the incidence and the prevalence of allergic diseases over the last several decades. Environmental triggers including risk factors (e.g., pollution), the loss of rural living conditions (e.g., farming conditions), and nutritional status (e.g., maternal, breastfeeding) are considered major contributors to this increase. The influences of these environmental factors are thought to be mediated by epigenetic mechanisms which are heritable, reversible, and biologically relevant biochemical modifications of the chromatin carrying the genetic information without changing the nucleotide sequence of the genome. An important feature characterizing epigenetically-mediated processes is the existence of a time frame where the induced effects are the strongest and therefore most crucial. This period between conception, pregnancy, and the first years of life (e.g., first 1000 days) is considered the optimal time for environmental factors, such as nutrition, to exert their beneficial epigenetic effects. In the current review, we discussed the impact of the exposure to bacteria, viruses, parasites, fungal components, microbiome metabolites, and specific nutritional components (e.g., polyunsaturated fatty acids (PUFA), vitamins, plant- and animal-derived microRNAs, breast milk) on the epigenetic patterns related to allergic manifestations. We gave insight into the epigenetic signature of bioactive milk components and the effects of specific nutrition on neonatal T cell development. Several lines of evidence suggest that atypical metabolic reprogramming induced by extrinsic factors such as allergens, viruses, pollutants, diet, or microbiome might drive cellular metabolic dysfunctions and defective immune responses in allergic disease. Therefore, we described the current knowledge on the relationship between immunometabolism and allergy mediated by epigenetic mechanisms. The knowledge as presented will give insight into epigenetic changes and the potential of maternal and post-natal nutrition on the development of allergic disease.


2019 ◽  
Author(s):  
Zhang Lee ◽  
Zengjian Wang ◽  
Johannes Lang ◽  
Sun Xinyu ◽  
Yao-Ting Sung

Pancreatic carcinoma is being recognized to be responsible for an increasing number of cancer-related deaths, especially in the western world. A deluge of risk factors have been described in the literature. Some of the important ones include smoking, alcohol and metabolic diseases like obesity. It also poses challenges in diagnosis and treatment despite recent advances in diagnostic, surgical and other therapeutic advancements. This is a narrative review of the findings of multiple studies that were retrieved from electronic databases like PubMed, Google Scholar, Scopus, Medline, Embase, and Cochrane databases. We summarize the current knowledge regarding the epidemiology and various risk factors for the development of pancreatic carcinoma.


2012 ◽  
pp. 61-83 ◽  
Author(s):  
M. Ershov

According to the latest forecasts, it will take 10 years for the world economy to get back to “decent shape”. Some more critical estimates suggest that the whole western world will have a “colossal mess” within the next 5–10 years. Regulators of some major countries significantly and over a short time‑period changed their forecasts for the worse which means that uncertainty in the outlook for the future persists. Indeed, the intensive anti‑crisis measures have reduced the severity of the past problems, however the problems themselves have not disappeared. Moreover, some of them have become more intense — the eurocrisis, excessive debts, global liquidity glut against the backdrop of its deficit in some of market segments. As was the case prior to the crisis, derivatives and high‑risk operations with “junk” bonds grow; budget problems — “fiscal cliff” in the US — and other problems worsen. All of the above forces the regulators to take unprecedented (in their scope and nature) steps. Will they be able to tackle the problems which emerge?


2020 ◽  
Vol 23 (26) ◽  
pp. 2945-2959 ◽  
Author(s):  
Xiangping Deng ◽  
Yijiao Peng ◽  
Jingduo Zhao ◽  
Xiaoyong Lei ◽  
Xing Zheng ◽  
...  

Rapid tumor growth is dependent on the capability of tumor blood vessels and glycolysis to provide oxygen and nutrients. Tumor hypoxia is a common characteristic of many solid tumors, and it essentially happens when the growth of the tumor exceeds the concomitant angiogenesis. Hypoxia-inducible factor 1 (HIF-1) as the critical transcription factor in hypoxia regulation is activated to adapt to this hypoxia situation. Flavonoids, widely distributed in plants, comprise many polyphenolic secondary metabolites, possessing broadspectrum pharmacological activities, including their potentiality as anticancer agents. Due to their low toxicity, intense efforts have been made for investigating natural flavonoids and their derivatives that can be used as HIF-1α inhibitors for cancer therapy during the past few decades. In this review, we sum up the findings concerning the inhibition of HIF-1α by natural flavonoids in the last few years and propose the idea of designing tumor vascular and glycolytic multi-target inhibitors with HIF-1α as one of the targets.


Micromachines ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 287
Author(s):  
Ye Lin Park ◽  
Kiwon Park ◽  
Jae Min Cha

Over the past decades, a number of bone tissue engineering (BTE) approaches have been developed to address substantial challenges in the management of critical size bone defects. Although the majority of BTE strategies developed in the laboratory have been limited due to lack of clinical relevance in translation, primary prerequisites for the construction of vascularized functional bone grafts have gained confidence owing to the accumulated knowledge of the osteogenic, osteoinductive, and osteoconductive properties of mesenchymal stem cells and bone-relevant biomaterials that reflect bone-healing mechanisms. In this review, we summarize the current knowledge of bone-healing mechanisms focusing on the details that should be embodied in the development of vascularized BTE, and discuss promising strategies based on 3D-bioprinting technologies that efficiently coalesce the abovementioned main features in bone-healing systems, which comprehensively interact during the bone regeneration processes.


Immuno ◽  
2021 ◽  
Vol 1 (2) ◽  
pp. 78-90
Author(s):  
Johannes Burtscher ◽  
Grégoire P. Millet

Like in other neurodegenerative diseases, protein aggregation, mitochondrial dysfunction, oxidative stress and neuroinflammation are hallmarks of Parkinson’s disease (PD). Differentiating characteristics of PD include the central role of α-synuclein in the aggregation pathology, a distinct vulnerability of the striato-nigral system with the related motor symptoms, as well as specific mitochondrial deficits. Which molecular alterations cause neurodegeneration and drive PD pathogenesis is poorly understood. Here, we summarize evidence of the involvement of three interdependent factors in PD and suggest that their interplay is likely a trigger and/or aggravator of PD-related neurodegeneration: hypoxia, acidification and inflammation. We aim to integrate the existing knowledge on the well-established role of inflammation and immunity, the emerging interest in the contribution of hypoxic insults and the rather neglected effects of brain acidification in PD pathogenesis. Their tight association as an important aspect of the disease merits detailed investigation. Consequences of related injuries are discussed in the context of aging and the interaction of different brain cell types, in particular with regard to potential consequences on the vulnerability of dopaminergic neurons in the substantia nigra. A special focus is put on the identification of current knowledge gaps and we emphasize the importance of related insights from other research fields, such as cancer research and immunometabolism, for neurodegeneration research. The highlighted interplay of hypoxia, acidification and inflammation is likely also of relevance for other neurodegenerative diseases, despite disease-specific biochemical and metabolic alterations.


2021 ◽  
Vol 22 (6) ◽  
pp. 2950
Author(s):  
Beatrycze Nowicka ◽  
Agnieszka Trela-Makowej ◽  
Dariusz Latowski ◽  
Kazimierz Strzalka ◽  
Renata Szymańska

Plant prenyllipids, especially isoprenoid chromanols and quinols, are very efficient low-molecular-weight lipophilic antioxidants, protecting membranes and storage lipids from reactive oxygen species (ROS). ROS are byproducts of aerobic metabolism that can damage cell components, they are also known to play a role in signaling. Plants are particularly prone to oxidative damage because oxygenic photosynthesis results in O2 formation in their green tissues. In addition, the photosynthetic electron transfer chain is an important source of ROS. Therefore, chloroplasts are the main site of ROS generation in plant cells during the light reactions of photosynthesis, and plastidic antioxidants are crucial to prevent oxidative stress, which occurs when plants are exposed to various types of stress factors, both biotic and abiotic. The increase in antioxidant content during stress acclimation is a common phenomenon. In the present review, we describe the mechanisms of ROS (singlet oxygen, superoxide, hydrogen peroxide and hydroxyl radical) production in chloroplasts in general and during exposure to abiotic stress factors, such as high light, low temperature, drought and salinity. We highlight the dual role of their presence: negative (i.e., lipid peroxidation, pigment and protein oxidation) and positive (i.e., contribution in redox-based physiological processes). Then we provide a summary of current knowledge concerning plastidic prenyllipid antioxidants belonging to isoprenoid chromanols and quinols, as well as their structure, occurrence, biosynthesis and function both in ROS detoxification and signaling.


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