scholarly journals Dual Roles of IL-27 in Cancer Biology and Immunotherapy

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Marina Fabbi ◽  
Grazia Carbotti ◽  
Silvano Ferrini
Keyword(s):  
Cell Proliferation ◽  
Cancer Biology ◽  
Cytotoxic T Lymphocyte ◽  
Biological Activities ◽  
Experimental Models ◽  
Dual Roles ◽  
Angiogenic Potential ◽  
Potential Applications ◽  
Regulatory Functions ◽  
Acting In Concert

IL-27 is a pleiotropic two-chain cytokine, composed of EBI3 and IL-27p28 subunits, which is structurally related to both IL-12 and IL-6 cytokine families. IL-27 acts through a heterodimer receptor consisting of IL-27Rα(WSX1) and gp130 chains, which mediate signaling predominantly through STAT1 and STAT3. IL-27 was initially reported as an immune-enhancing cytokine that supports CD4+T cell proliferation, T helper (Th)1 cell differentiation, and IFN-γproduction, acting in concert with IL-12. However, subsequent studies demonstrated that IL-27 displays complex immune-regulatory functions, which may result in either proinflammatory or anti-inflammatory effects in relationship to the biological context and experimental models considered. Several pieces of evidence, obtained in preclinical tumor models, indicated that IL-27 has a potent antitumor activity, related not only to the induction of tumor-specific Th1 and cytotoxic T lymphocyte (CTL) responses but also to direct inhibitory effects on tumor cell proliferation, survival, invasiveness, and angiogenic potential. Nonetheless, given its immune-regulatory functions, the effects of IL-27 on cancer may be dual and protumor effects may also occur. Here, we will summarize IL-27 biological activities and its functional overlaps with the IFNs and discuss its dual role in tumors in the light of potential applications to cancer immunotherapy.

scholarly journals SALL Proteins; Common and Antagonistic Roles in Cancer

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6292
Author(s):  
Claudia Álvarez ◽  
Aracelly Quiroz ◽  
Diego Benítez-Riquelme ◽  
Elizabeth Riffo ◽  
Ariel F. Castro ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Genetic Disorders ◽  
Family Members ◽  
Tumor Development ◽  
Cancer Biomarkers ◽  
Regulatory Mechanisms ◽  
Dual Roles ◽  
Human Genetic Disorders

SALL proteins are a family of four conserved C2H2 zinc finger transcription factors that play critical roles in organogenesis during embryonic development. They regulate cell proliferation, survival, migration, and stemness; consequently, they are involved in various human genetic disorders and cancer. SALL4 is a well-recognized oncogene; however, SALL1–3 play dual roles depending on the cancer context and stage of the disease. Current reviews of SALLs have focused only on SALL2 or SALL4, lacking an integrated view of the SALL family members in cancer. Here, we update the recent advances of the SALL members in tumor development, cancer progression, and therapy, highlighting the synergistic and/or antagonistic functions they perform in similar cancer contexts. We identified common regulatory mechanisms, targets, and signaling pathways in breast, brain, liver, colon, blood, and HPV-related cancers. In addition, we discuss the potential of the SALL family members as cancer biomarkers and in the cancer cells’ response to therapies. Understanding SALL proteins’ function and relationship will open new cancer biology, clinical research, and therapy perspectives.

scholarly journals Immunomodulatory Nanomedicine for the Treatment of Atherosclerosis

2021 ◽  
Vol 10 (14) ◽  
pp. 3185
Author(s):  
Linsey J. F. Peters ◽  
Alexander Jans ◽  
Matthias Bartneck ◽  
Emiel P. C. van der Vorst
Keyword(s):  
Cell Proliferation ◽  
Drug Carriers ◽  
Research Field ◽  
General Introduction ◽  
Cellular Receptors ◽  
Cellular Processes ◽  
Potential Applications ◽  
Current Therapies ◽  
Based Medicine ◽  
Physiological Systems

Atherosclerosis is the main underlying cause of cardiovascular diseases (CVDs), which remain the number one contributor to mortality worldwide. Although current therapies can slow down disease progression, no treatment is available that can fully cure or reverse atherosclerosis. Nanomedicine, which is the application of nanotechnology in medicine, is an emerging field in the treatment of many pathologies, including CVDs. It enables the production of drugs that interact with cellular receptors, and allows for controlling cellular processes after entering these cells. Nanomedicine aims to repair, control and monitor biological and physiological systems via nanoparticles (NPs), which have been shown to be efficient drug carriers. In this review we will, after a general introduction, highlight the advantages and limitations of the use of such nano-based medicine, the potential applications and targeting strategies via NPs. For example, we will provide a detailed discussion on NPs that can target relevant cellular receptors, such as integrins, or cellular processes related to atherogenesis, such as vascular smooth muscle cell proliferation. Furthermore, we will underline the (ongoing) clinical trials focusing on NPs in CVDs, which might bring new insights into this research field.

scholarly journals Panax notoginseng saponins promote endothelial progenitor cell angiogenesis via the Wnt/β-catenin pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Peiqi Zhu ◽  
Weidong Jiang ◽  
Shixi He ◽  
Tao Zhang ◽  
Fengchun Liao ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Panax Notoginseng ◽  
Tube Formation ◽  
Optimal Concentration ◽  
Mrna Levels ◽  
Panax Notoginseng Saponins ◽  
Endothelial Progenitor ◽  
Angiogenic Potential ◽  
Craniomaxillofacial Surgery ◽  
And Migration

Abstract Background Distraction osteogenesis (DO) is an effective treatment in craniomaxillofacial surgery. However, the issue of sufficient blood supply at the regeneration tissue has limited its wide application. Panax notoginseng saponins (PNS) is a Traditional Chinese Medicine that is commonly used to treat a range of angiogenic diseases. However, the mechanisms whereby PNS alters angiogenesis in endothelial progenitor cells (EPCs) have yet to be clarified. Methods EPCs were identified by immunofluorescence, confirmed by their uptake of fluorescently labeled Dil-ac-LDL and FITC-UEA-1. EPCs were treated with different concentrations of PNS, and the effects of PNS on cell proliferation were measured on the optimal concentration of PNS determined. The effects of PNS on angiogenesis and migration, angiogenic cytokines mRNA expression and the proteins of the Wnt pathway were investigated. Then knocked down β-catenin in EPCs and treated with the optimum concentrational PNS, their angiogenic potential was evaluated in tube formation and migration assays. In addition, the expression of cytokines associated with angiogenesis and Wnt/β-catenin was then assessed via WB and RT-qPCR. Results We were able to determine the optimal concentration of PNS in the promotion of cell proliferation, tube formation, and migration to be 6.25 mg/L. PNS treatment increased the mRNA levels of VEGF, bFGF, VE-Cadherin, WNT3a, LRP5, β-catenin, and TCF4. After knocked down β-catenin expression, we found that PNS could sufficient to partially reverse the suppression of EPC angiogenesis. Conclusions Overall, 6.25 mg/L PNS can promote EPC angiogenesis via Wnt/β-catenin signaling pathway activation.

scholarly journals The Brown Seaweeds of Scotland, Their Importance and Applications

Environments ◽  
2021 ◽  
Vol 8 (6) ◽  
pp. 59
Author(s):  
Omar Al-Dulaimi ◽  
Mostafa E. Rateb ◽  
Andrew S. Hursthouse ◽  
Gary Thomson ◽  
Mohammed Yaseen
Keyword(s):  
Waste Treatment ◽  
Biological Activities ◽  
Chemical Diversity ◽  
Great Opportunity ◽  
Brown Seaweeds ◽  
Extraction And Separation ◽  
The Status ◽  
Potential Applications ◽  
The Uk ◽  
Phytochemical Profiles

More than 50% of the UK coastline is situated in Scotland under legislative jurisdiction; therefore, there is a great opportunity for regionally focused economic development by the rational use of sustainable marine bio-sources. We review the importance of seaweeds in general, and more specifically, wrack brown seaweeds which are washed from the sea and accumulated in the wrack zone and their economic impact. Rules and regulations governing the harvesting of seaweed, potential sites for harvesting, along with the status of industrial application are discussed. We describe extraction and separation methods of natural products from these seaweeds along with their phytochemical profiles. Many potential applications for these derivatives exist in agriculture, energy, nutrition, biomaterials, waste treatment (composting), pharmaceuticals, cosmetics and other applications. The chemical diversity of the natural compounds present in these seaweeds is an opportunity to further investigate a range of chemical scaffolds, evaluate their biological activities, and develop them for better pharmaceutical or biotechnological applications. The key message is the significant opportunity for the development of high value products from a seaweed processing industry in Scotland, based on a sustainable resource, and locally regulated.

scholarly journals Evidence for a Negative Correlation between Human Reactive Enamine-Imine Intermediate Deaminase A (RIDA) Activity and Cell Proliferation Rate: Role of Lysine Succinylation of RIDA

2021 ◽  
Vol 22 (8) ◽  
pp. 3804
Author(s):  
Luisa Siculella ◽  
Laura Giannotti ◽  
Benedetta Di Chiara Stanca ◽  
Matteo Calcagnile ◽  
Alessio Rochira ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Negative Correlation ◽  
Cancer Biology ◽  
Human Tumor ◽  
In Silico Analysis ◽  
Proliferation Rate ◽  
Reactive Intermediate ◽  
Cell Proliferation Rate

Reactive intermediate deaminase (Rid) proteins are enzymes conserved in all domains of life. UK114, a mammalian member of RidA subfamily, has been firstly identified as a component of liver perchloric acid-soluble proteins (L-PSP). Although still poorly defined, several functions have been attributed to the mammalian protein UK114/RIDA, including the reactive intermediate deamination activity. The expression of UK114/RIDA has been observed in some tumors, arousing interest in this protein as an evaluable tumor marker. However, other studies reported a negative correlation between UK114/RIDA expression, tumor differentiation degree and cell proliferation. This work addressed the question of UK114/RIDA expression in human non-tumor HEK293 cell lines and in some human tumor cell lines. Here we reported that human RIDA (hRIDA) was expressed in all the analyzed cell line and subjected to lysine (K-)succinylation. In HEK293, hRIDA K-succinylation was negatively correlated to the cell proliferation rate and was under the control of SIRT5. Moreover, K-succinylation clearly altered hRIDA quantification by immunoblotting, explaining, at least in part, some discrepancies about RIDA expression reported in previous studies. We found that hRIDA was able to deaminate reactive enamine-imine intermediates and that K-succinylation drastically reduced deaminase activity. As predicted by in silico analysis, the observed reduction of deaminase activity has been related to the drastic alterations of hRIDA structure inferred by K-succinylation. The role of hRIDA and the importance of its K-succinylation in cell metabolism, especially in cancer biology, have been discussed.

scholarly journals The Structure–Properties–Cytotoxicity Interplay: A Crucial Pathway to Determining Graphene Oxide Biocompatibility

2021 ◽  
Vol 22 (10) ◽  
pp. 5401
Author(s):  
Marta Dziewięcka ◽  
Mirosława Pawlyta ◽  
Łukasz Majchrzycki ◽  
Katarzyna Balin ◽  
Sylwia Barteczko ◽  
...  
Keyword(s):  
Graphene Oxide ◽  
Defense Mechanisms ◽  
Physicochemical Analysis ◽  
Experimental Models ◽  
Acheta Domesticus ◽  
Synthesis Process ◽  
Synthesis Methods ◽  
Toxicity Potential ◽  
Potential Applications

Interest in graphene oxide nature and potential applications (especially nanocarriers) has resulted in numerous studies, but the results do not lead to clear conclusions. In this paper, graphene oxide is obtained by multiple synthesis methods and generally characterized. The mechanism of GO interaction with the organism is hard to summarize due to its high chemical activity and variability during the synthesis process and in biological buffers’ environments. When assessing the biocompatibility of GO, it is necessary to take into account many factors derived from nanoparticles (structure, morphology, chemical composition) and the organism (species, defense mechanisms, adaptation). This research aims to determine and compare the in vivo toxicity potential of GO samples from various manufacturers. Each GO sample is analyzed in two concentrations and applied with food. The physiological reactions of an easy model Acheta domesticus (cell viability, apoptosis, oxidative defense, DNA damage) during ten-day lasting exposure were observed. This study emphasizes the variability of the GO nature and complements the biocompatibility aspect, especially in the context of various GO-based experimental models. Changes in the cell biomarkers are discussed in light of detailed physicochemical analysis.

scholarly journals Recent Findings in Azaphilone Pigments

2021 ◽  
Vol 7 (7) ◽  
pp. 541
Author(s):  
Lúcia P. S. Pimenta ◽  
Dhionne C. Gomes ◽  
Patrícia G. Cardoso ◽  
Jacqueline A. Takahashi
Keyword(s):  
Water Solubility ◽  
Biological Activities ◽  
Low Cost ◽  
Scale Up ◽  
Structural Diversity ◽  
Downstream Processing ◽  
Global Market ◽  
Yield Improvement ◽  
Potential Applications ◽  
New Compounds

Filamentous fungi are known to biosynthesize an extraordinary range of azaphilones pigments with structural diversity and advantages over vegetal-derived colored natural products such agile and simple cultivation in the lab, acceptance of low-cost substrates, speed yield improvement, and ease of downstream processing. Modern genetic engineering allows industrial production, providing pigments with higher thermostability, water-solubility, and promising bioactivities combined with ecological functions. This review, covering the literature from 2020 onwards, focuses on the state-of-the-art of azaphilone dyes, the global market scenario, new compounds isolated in the period with respective biological activities, and biosynthetic pathways. Furthermore, we discussed the innovations of azaphilone cultivation and extraction techniques, as well as in yield improvement and scale-up. Potential applications in the food, cosmetic, pharmaceutical, and textile industries were also explored.

miR-3156-5p Enhances Hypoxia-Induced Angiogenesis in Hepatocellular Carcinoma via Modulating the SOCS5/HIF-1α/VEGF Pathway

2021 ◽  
Author(s):  
Bin Tie ◽  
Zheng Guo ◽  
Li Li ◽  
Wenhui Wang ◽  
Rong Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Endothelial Cells ◽  
Colony Formation ◽  
Cell Counting ◽  
Angiogenic Potential ◽  
Reverse Transcription Pcr ◽  
Vegf Pathway ◽  
Formation Experiment ◽  
Hcc Cells

Abstract Background: MicroRNAs (miRNAs) are dysregulated in hypoxia-induced hepatocellular carcinoma (HCC). This study probed the regulatory mechanism of miR-3156-5p on HCC under hypoxia. Methods: HCC cells (HepG2) were exposed to normoxia or hypoxia, and the conditioned medium (CM) of HepG2 was applied. Quantitative reverse transcription PCR (qRT-PCR) was implemented to analyze the miR-3156-5p profile. The cell counting kit-8 (CCK-8) assay and the colony formation experiment were conducted to measure cell proliferation, colony formation, and angiogenesis. Results: The results manifested that miR-3156-5p was up-regulated in HCC cells and endothelial cells under hypoxia, and up-regulating miR-3156-5p boosted HCC cell proliferation, endothelial cell angiogenesis, and HIF-1α/VEGF expression. Conclusions: miR-3156-5p activates the HIF-1α/VEGF pathway by hampering SOCS5, thereby enhancing the angiogenic potential of hypoxia-induced endothelial cells in HCC cells.

TGFβ: Signaling Blockade for Cancer Immunotherapy

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Szu-Ying Chen ◽  
Ons Mamäi ◽  
Rosemary J. Akhurst
Keyword(s):  
Cancer Biology ◽  
Transforming Growth Factor ◽  
Biological Activities ◽  
Tumor Stroma ◽  
Transforming Growth Factor Β ◽  
Therapeutic Window ◽  
Annual Review ◽  
Publication Date ◽  
Tgfβ Signaling ◽  
Mesenchymal Transformation

Discovered over four decades ago, transforming growth factor β (TGFβ) is a potent pleiotropic cytokine that has context-dependent effects on most cell types. It acts as a tumor suppressor in some cancers and/or supports tumor progression and metastasis through its effects on the tumor stroma and immune microenvironment. In TGFβ-responsive tumors it can promote invasion and metastasis through epithelial-mesenchymal transformation, the appearance of cancer stem cell features, and resistance to many drug classes, including checkpoint blockade immunotherapies. Here we consider the biological activities of TGFβ action on different cells of relevance toward improving immunotherapy outcomes for patients, with a focus on the adaptive immune system. We discuss recent advances in the development of drugs that target the TGFβ signaling pathway in a tumor-specific or cell type–specific manner to improve the therapeutic window between response rates and adverse effects. Expected final online publication date for the Annual Review of Cancer Biology, Volume 6 is April 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Studying the central control of food intake and obesity in rats

2009 ◽  
Vol 22 (1) ◽  
pp. 163-171 ◽  
Author(s):  
Eliane Beraldi Ribeiro
Keyword(s):  
Genetic Model ◽  
Monosodium Glutamate ◽  
Extracellular Fluid ◽  
Experimental Models ◽  
Central Control ◽  
Physiological Control ◽  
Potential Applications ◽  
The Central Nervous System ◽  
Immunoblot Technique ◽  
Feeding Control

The central nervous system regulates energy intake and expenditure through a complex network of neurotransmitters and neuromodulators. It is of great interest to understand the relevance of these systems to the physiological control of energy balance and to the disturbances of obesity. The present paper discusses some of the methods to address this field used at the laboratory of Endocrine Physiology of Universidade Federal de São Paulo. Initially, different experimental models of rat obesity are presented, namely the hypothalamic induced monosodium glutamate model, the Zucker genetic model, and the dietary model. The principles of brain microdialysis are also presented, the technique applied to obtain representative samples of the extracellular fluid of brain sites involved in feeding control. The microdialysate levels of serotonin, an important anorexigenic neurotransmitter, are determined by HPLC with electrochemical detection. The immunoblot technique (Western blot) is used to determine hypothalamic levels of proteins relevant to the anorexigenic effect of serotonin and to analyze the acute activation of the insulin signaling cascade in the hypothalamus. The final section addresses the potential applications of proteomics in the study of the central control of feeding.

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