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1.
Primary de-differentiated, trans-differentiated and undifferentiated melanomas: overview of the clinicopathological, immunohistochemical and molecular spectrum.
Ferreira, I, Arends, MJ, van der Weyden, L, Adams, DJ, Brenn, T
Histopathology. 2022;(1):135-149
Abstract
Primary cutaneous and mucosal melanoma shows a wide histological spectrum. The correct diagnosis depends upon the demonstration of melanocytic differentiation by recognition of an associated in-situ component or immunohistochemical evidence of a melanocytic phenotype using conventional melanocytic markers, such as S-100, SOX10, Melan-A and HMB-45. Exceptionally, melanomas lose their melanocytic phenotype, at least focally, and show differentiation towards other lineages. Review of the literature shows that de- and trans-differentiation in melanoma is rare but probably under-recognised and under-reported. These often large and frequently ulcerated tumours affect adults and show a wide anatomical distribution, including mucosal sites, although there is a predilection for sun-damaged skin of the head and neck. Histologically, the tumours are biphasic and contain a pre-existing conventional melanoma. The de-differentiated component closely resembles atypical fibroxanthoma, both morphologically and immunohistochemically. Trans-differentiated melanoma may show rhabdomyosarcomatous or spindle cell carcinomatous features. Undifferentiated melanomas are similar tumours in which the conventional melanoma component is absent. Their diagnosis depends entirely upon the clinical context and identification of a classical melanoma driver gene mutation, i.e. BRAF V600E. The diagnosis of these rare and unusual tumours is challenging, and requires thorough tumour sampling and recognition of the background of a pre-existing but often focal conventional melanoma together with molecular analysis.
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2.
Circular RNAs: Rising stars in lipid metabolism and lipid disorders.
Yu, G, Yang, Z, Peng, T, Lv, Y
Journal of cellular physiology. 2021;(7):4797-4806
Abstract
The underlying mechanisms of circular RNAs (circRNAs) in lipid metabolism regulation and the pathogenesis of lipid disorder diseases are clarified in this review. circRNAs are produced from host genes by back splicing and are mainly degraded by RNase L. circRNAs act as molecular sponges or scaffolds that bind with microRNAs or proteins and thus affect the intracorporeal processes of lipid metabolism. CircRNA_11897 and circSAMD4A facilitated adipogenesis while circH19 and circRNA_26852 accelerated adipolysis in adipose tissue. CircSAMD4A promoted the differentiation of preadipocytes, but circH19 and circFUT10 inhibited this differentiation. CircFUT10 also promoted the proliferation of preadipocytes. CiRS-133 fostered the browning of white adipose tissue. CircACC1, circRNA_021412, circRNA_0046366, and circRNA_0046367 promoted the mitochondrial β-oxidation of fatty acids in hepatocytes. CircRNA_021412 suppressed the synthesis of triglycerides in hepatocytes. CircScd1 inhibited hepatic lipid droplet formation. circ_0092317, circ_0003546, circ_0028198, circ_0092317, and circACC1 probably reduced cholesterol efflux from macrophages. circ_0037251 likely promoted lipid accumulation and inhibited lipophagy in macrophages. circRNAs participate in lipid metabolism regulation and affect the development of lipid disorder diseases.
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3.
The role of statins in the differentiation and function of bone cells.
Chamani, S, Liberale, L, Mobasheri, L, Montecucco, F, Al-Rasadi, K, Jamialahmadi, T, Sahebkar, A
European journal of clinical investigation. 2021;(7):e13534
Abstract
BACKGROUND Statins are 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors blocking cholesterol biosynthesis in hepatic cells, thereby causing an increase in low-density lipoprotein (LDL) receptors resulting in enhanced uptake and clearance of atherogenic LDL-cholesterol (LDL-C) from the blood. Accordingly, statins decrease the risk of developing atherosclerosis and its acute complications, such as acute myocardial infarction and ischaemic stroke. Besides the LDL-C-lowering impact, statins also have other so-called pleiotropic effects. Among them, the ability to modulate differentiation and function of bone cells and exert direct effects on osteosynthesis factors. Specifically, earlier studies have shown that statins cause in vitro and in vivo osteogenic differentiation. DESIGN The most relevant papers on the bone-related 'pleiotropic' effects of statins were selected following literature search in databases and were reveiwed. RESULTS Statins increase the expression of many mediators involved in bone metabolism including bone morphogenetic protein-2 (BMP-2), glucocorticoids, transforming growth factor-beta (TGF-β), alkaline phosphatase (ALP), type I collagen and collagenase-1. As a result, they enhance bone formation and improve bone mineral density by modulating osteoblast and osteoclast differentiation. CONCLUSION This review summarizes the literature exploring bone-related 'pleiotropic' effects of statins and suggests an anabolic role in the bone tissue for this drug class. Accordingly, current knowledge encourages further clinical trials to assess the therapeutic potential of statins in the treatment of bone disorders, such as arthritis and osteoporosis.
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4.
ABA and Bud Dormancy in Perennials: Current Knowledge and Future Perspective.
Pan, W, Liang, J, Sui, J, Li, J, Liu, C, Xin, Y, Zhang, Y, Wang, S, Zhao, Y, Zhang, J, et al
Genes. 2021;(10)
Abstract
Bud dormancy is an evolved trait that confers adaptation to harsh environments, and affects flower differentiation, crop yield and vegetative growth in perennials. ABA is a stress hormone and a major regulator of dormancy. Although the physiology of bud dormancy is complex, several advancements have been achieved in this field recently by using genetics, omics and bioinformatics methods. Here, we review the current knowledge on the role of ABA and environmental signals, as well as the interplay of other hormones and sucrose, in the regulation of this process. We also discuss emerging potential mechanisms in this physiological process, including epigenetic regulation.
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5.
Synthetic Retinoids as Potential Therapeutics in Prostate Cancer-An Update of the Last Decade of Research: A Review.
Hałubiec, P, Łazarczyk, A, Szafrański, O, Bohn, T, Dulińska-Litewka, J
International journal of molecular sciences. 2021;(19)
Abstract
Prostate cancer (PC) is the second most common tumor in males. The search for appropriate therapeutic options against advanced PC has been in process for several decades. Especially after cessation of the effectiveness of hormonal therapy (i.e., emergence of castration-resistant PC), PC management options have become scarce and the prognosis is poor. To overcome this stage of disease, an array of natural and synthetic substances underwent investigation. An interesting and promising class of compounds constitutes the derivatives of natural retinoids. Synthesized on the basis of the structure of retinoic acid, they present unique and remarkable properties that warrant their investigation as antitumor drugs. However, there is no up-to-date compilation that consecutively summarizes the current state of knowledge about synthetic retinoids with regard to PC. Therefore, in this review, we present the results of the experimental studies on synthetic retinoids conducted within the last decade. Our primary aim is to highlight the molecular targets of these compounds and to identify their potential promise in the treatment of PC.
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6.
Current practice in patients with differentiated thyroid cancer.
Schlumberger, M, Leboulleux, S
Nature reviews. Endocrinology. 2021;(3):176-188
Abstract
Considerable changes have occurred in the management of differentiated thyroid cancer (DTC) during the past four decades, based on improved knowledge of the biology of DTC and on advances in therapy, including surgery, the use of radioactive iodine (radioiodine), thyroid hormone treatment and availability of recombinant human TSH. Improved diagnostic tools are available, including determining serum levels of thyroglobulin, neck ultrasonography, imaging (CT, MRI, SPECT-CT and PET-CT), and prognostic classifications have been improved. Patients with low-risk DTC, in whom the risk of thyroid cancer death is <1% and most recurrences can be cured, currently represent the majority of patients. By contrast, patients with high-risk DTC represent 5-10% of all patients. Most thyroid cancer-related deaths occur in this group of patients and recurrences are frequent. Patients with high-risk DTC require more aggressive treatment and follow-up than patients with low-risk DTC. Finally, the strategy for treating patients with intermediate-risk DTC is frequently defined on a case-by-case basis. Prospective trials are needed in well-selected patients with DTC to demonstrate the extent to which treatment and follow-up can be limited without increasing the risk of recurrence and thyroid cancer-related death.
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7.
Stem metabolism: Insights from oncometabolism and vice versa.
Rodrigues, AS, Pereira, SL, Ramalho-Santos, J
Biochimica et biophysica acta. Molecular basis of disease. 2020;(7):165760
Abstract
Metabolism, is a transversal hot research topic in different areas, resulting in the integration of cellular needs with external cues, involving a highly coordinated set of activities in which nutrients are converted into building blocks for macromolecules, energy currencies and biomass. Importantly, cells can adjust different metabolic pathways defining its cellular identity. Both cancer cell and embryonic stem cells share the common hallmark of high proliferative ability but while the first represent a huge social-economic burden the second symbolize a huge promise. Importantly, research on both fields points out that stem cells share common metabolic strategies with cancer cells to maintain their identity as well as proliferative capability and, vice versa cancer cells also share common strategies regarding pluripotent markers. Moreover, the Warburg effect can be found in highly proliferative non-cancer stem cells as well as in embryonic stem cells that are primed towards differentiation, while a bivalent metabolism is characteristic of embryonic stem cells that are in a true naïve pluripotent state and cancer stem cells can also range from glycolysis to oxidative phosphorylation. Therefore, this review aims to highlight major metabolic similarities between cancer cells and embryonic stem cells demonstrating that they have similar strategies in both signaling pathways regulation as well as metabolic profiles while focusing on key metabolites.
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8.
Vitamin D and Other Differentiation-promoting Agents as Neoadjuvants for Photodynamic Therapy of Cancer.
Maytin, EV, Hasan, T
Photochemistry and photobiology. 2020;(3):529-538
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Abstract
The efficacy of photodynamic therapy (PDT) using aminolevulinic acid (ALA), which is preferentially taken up by cancerous cells and converted to protoporphyrin IX (PpIX), can be substantially improved by pretreating the tumor cells with vitamin D (Vit D). Vit D is one of several "differentiation-promoting agents" that can promote the preferential accumulation of PpIX within the mitochondria of neoplastic cells, making them better targets for PDT. This article provides a historical overview of how the concept of using combination agents ("neoadjuvants") for PDT evolved, from initial discoveries about neoadjuvant effects of methotrexate and fluorouracil to later studies to determine how vitamin D and other agents actually work to augment PDT efficacy. While this review focuses mainly on skin cancer, it includes a discussion about how these concepts may be applied more broadly toward improving PDT outcomes in other types of cancer.
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9.
Phytochemicals impact on osteogenic differentiation of mesenchymal stem cells.
Sharifi, S, Moghaddam, FA, Abedi, A, Maleki Dizaj, S, Ahmadian, S, Abdolahinia, ED, Khatibi, SMH, Samiei, M
BioFactors (Oxford, England). 2020;(6):874-893
Abstract
Medicinal plants have always been utilized for the prevention and treatment of the spread of different diseases all around the world. To name some traditional medicine that has been used over centuries, we can refer to phytochemicals such as naringin, icariin, genistein, and resveratrol gained from plants. Osteogenic differentiation and mineralization of stem cells can be the result of specific bioactive compounds from plants. One of the most appealing choices for therapy can be mesenchymal stem cells (MSCs) because it has a great capability of self-renewal and differentiation into three descendants, namely, endoderm, mesoderm, and ectoderm. Stem cell gives us the glad tidings of great advances in tissue regeneration and transplantation field for treatment of diseases. Using plant bioactive phytochemicals also holds tremendous promises in treating diseases such as osteoporosis. The purpose of the present review article thus is to investigate what are the roles and consequences of phytochemicals on osteogenic differentiation of MSCs.
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10.
Epigenetic Regulators of Mesenchymal Stem/Stromal Cell Lineage Determination.
Cakouros, D, Gronthos, S
Current osteoporosis reports. 2020;(5):597-605
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Abstract
PURPOSE OF REVIEW Although many signalling pathways have been discovered to be essential in mesenchymal stem/stromal (MSC) differentiation, it has become increasingly clear in recent years that epigenetic regulation of gene transcription is a vital component of lineage determination, encompassing diet, lifestyle and parental influences on bone, fat and cartilage development. RECENT FINDINGS This review discusses how specific enzymes that modify histone methylation and acetylation or DNA methylation orchestrate the differentiation programs in lineage determination of MSC and the epigenetic changes that facilitate development of bone related diseases such as osteoporosis. The review also describes how environmental factors such as mechanical loading influence the epigenetic signatures of MSC, and how the use of chemical agents or small peptides can regulate epigenetic drift in MSC populations during ageing and disease. Epigenetic regulation of MSC lineage commitment is controlled through changes in enzyme activity, which modifies DNA and histone residues leading to alterations in chromatin structure. The co-ordinated epigenetic regulation of transcriptional activation and repression act to mediate skeletal tissue homeostasis, where deregulation of this process can lead to bone loss during ageing or osteoporosis.