scholarly journals Study of Natural Longlife Juvenility and Tissue Regeneration in Caudate Amphibians and Potential Application of Resulting Data in Biomedicine

2021 ◽  
Vol 9 (1) ◽  
pp. 2
Author(s):  
Eleonora N. Grigoryan
Keyword(s):  
Regenerative Medicine ◽  
Mammalian Cell ◽  
Tissue Regeneration ◽  
Potential Application ◽  
De Novo ◽  
Tissue Structure ◽  
Age Dependence ◽  
Cell Plasticity ◽  
Expression Of Genes ◽  
Different Levels

The review considers the molecular, cellular, organismal, and ontogenetic properties of Urodela that exhibit the highest regenerative abilities among tetrapods. The genome specifics and the expression of genes associated with cell plasticity are analyzed. The simplification of tissue structure is shown using the examples of the sensory retina and brain in mature Urodela. Cells of these and some other tissues are ready to initiate proliferation and manifest the plasticity of their phenotype as well as the correct integration into the pre-existing or de novo forming tissue structure. Without excluding other factors that determine regeneration, the pedomorphosis and juvenile properties, identified on different levels of Urodele amphibians, are assumed to be the main explanation for their high regenerative abilities. These properties, being fundamental for tissue regeneration, have been lost by amniotes. Experiments aimed at mammalian cell rejuvenation currently use various approaches. They include, in particular, methods that use secretomes from regenerating tissues of caudate amphibians and fish for inducing regenerative responses of cells. Such an approach, along with those developed on the basis of knowledge about the molecular and genetic nature and age dependence of regeneration, may become one more step in the development of regenerative medicine

Metabolism-driven post-translational modifications of H3K9 in early bovine embryos

Reproduction ◽  
2021 ◽  
Vol 162 (3) ◽  
pp. 181-191
Author(s):  
Jessica Ispada ◽  
Aldcejam Martins da Fonseca Junior ◽  
Otávio Luiz Ramos Santos ◽  
Camila Bruna de Lima ◽  
Erika Cristina dos Santos ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Developmental Stages ◽  
De Novo ◽  
Blastocyst Stage ◽  
Developmental Model ◽  
Bovine Embryos ◽  
Acetyl Coa ◽  
Post Translational Modifications ◽  
The Relationship ◽  
Different Levels

Metabolic and molecular profiles were reported as different for bovine embryos with distinct kinetics during the first cleavages. In this study, we used this same developmental model (fast vs slow) to determine if the relationship between metabolism and developmental kinetics affects the levels of acetylation or tri-methylation at histone H3 lysine 9 (H3K9ac and H3K9me3, respectively). Fast and slow developing embryos presented different levels of H3K9ac and H3K9me3 from the earliest stages of development (40 and 96 hpi) and up to the blastocyst stage. For H3K9me3, both groups of embryos presented a wave of demethylation and de novo methylation, although it was more pronounced in fast than slow embryos, resulting in blastocysts with higher levels of this mark. The H3K9ac reprogramming profile was distinct between kinetics groups. While slow embryos presented a wave of deacetylation, followed by an increase in this mark at the blastocyst stage, fast embryos reduced this mark throughout all the developmental stages studied. H3K9me3 differences corresponded to writer and eraser transcript levels, while H3K9ac patterns were explained by metabolism-related gene expression. To verify if metabolic differences could alter levels of H3K9ac, embryos were cultured with sodium-iodoacetate (IA) or dichloroacetate (DCA) to disrupt the glycolytic pathway or increase acetyl-CoA production, respectively. IA reduced H3K9ac while DCA increased H3K9ac in blastocysts. Concluding, H3K9me3 and H3K9ac patterns differ between embryos with different kinetics, the second one explained by metabolic pathways involved in acetyl-CoA production. So far, this is the first study demonstrating a relationship between metabolic differences and histone post-translational modifications in bovine embryos.

scholarly journals Il6/Sil6R Regulates Tnfα-Inflammatory Response In Synovial Fibroblasts Through Modulation of Transcriptional and Post-Transcriptional Mechanisms

2020 ◽  
Author(s):  
Alvaro Valin ◽  
Manuel J. Del Rey ◽  
Cristina Municio ◽  
Alicia Usategui ◽  
Marina Romero ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Mononuclear Cells ◽  
De Novo ◽  
Inflammatory Cells ◽  
Synovial Fibroblasts ◽  
Matrix Metalloproteases ◽  
P Value ◽  
Polymorphonuclear Cells ◽  
Expression Of Genes

Abstract Introduction: The clinical efficacy of specific interleukin-6 inhibitors has confirmed the central role of IL6 in rheumatoid arthritis (RA). However the local role of IL6, in particular in synovial fibroblasts (SF) as a direct cellular target to IL6/sIL6R signal is not well characterized. The purpose of the study was to characterize the crosstalk between TNFα and IL6/sIL6R signaling to the effector pro-inflammatory response of SF. Methods SF lines were stimulated with either TNFα or IL6 and sIL6R for the time and dose indicated for each experiment, and where indicated, cells were treated with inhibitors actinomycin D, adalimumab, ruxolitinib and cicloheximide. mRNA expression of cytokines, chemokines and matrix metalloproteases (MMPs) were analyzed by quantitative RT-PCR. Level of IL8 and CCL8 in culture supernatants was measured by ELISA. Mononuclear and polymorphonuclear cells migration assays were assesed by transwell using conditioned medium from SF cultures. Statistical analyses were performed as indicated in the corresponding figure legends and a p-value < 0.05 was considered statistically significant. Results IL6/sIL6R stimulation of TNFα treated SF cooperatively promotes the expression of mono- and lymphocytic chemokines such as IL6, CCL8 and CCL2, as well as matrix degrading enzymes such as MMP1, while inhibiting the induction of central neutrophil chemokines such as IL8. These changes in the pattern of chemokines expression resulted in reduced polymorphonuclear (PMN) and increased mononuclear cells (MNC) chemoattraction by SF. Mechanistic analyses of the temporal expression of genes demonstrated that the cooperative regulation mediated by these two factors is mostly induced through de novo transcriptional mechanisms activated by IL6/sIL6R. Furthermore, we also demonstrate that TNFα and IL6/sIL6R cooperation is partially mediated by the expression of secondary factors signaling through JAK/STAT pathways. Conclusions These results point out to a highly orchestrated response to IL6 in TNFα-induced SF and provide additional insights into the role of IL6/sIL6R in the context of RA, highlighting the contribution of IL6/sIL6R to the interplay of SF with other inflammatory cells.

scholarly journals Additive Manufacturing of Biopolymers for Tissue Engineering and Regenerative Medicine: An Overview, Potential Applications, Advancements, and Trends

2021 ◽  
Vol 2021 ◽  
pp. 1-20 ◽  
Author(s):  
Dhinakaran Veeman ◽  
M. Swapna Sai ◽  
P. Sureshkumar ◽  
T. Jagadeesha ◽  
L. Natrayan ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Additive Manufacturing ◽  
3D Printing ◽  
Regenerative Medicine ◽  
Tissue Regeneration ◽  
Three Dimensional ◽  
Porous Scaffolds ◽  
Wide Range ◽  
Potential Applications ◽  
Pharmaceutical Industries

As a technique of producing fabric engineering scaffolds, three-dimensional (3D) printing has tremendous possibilities. 3D printing applications are restricted to a wide range of biomaterials in the field of regenerative medicine and tissue engineering. Due to their biocompatibility, bioactiveness, and biodegradability, biopolymers such as collagen, alginate, silk fibroin, chitosan, alginate, cellulose, and starch are used in a variety of fields, including the food, biomedical, regeneration, agriculture, packaging, and pharmaceutical industries. The benefits of producing 3D-printed scaffolds are many, including the capacity to produce complicated geometries, porosity, and multicell coculture and to take growth factors into account. In particular, the additional production of biopolymers offers new options to produce 3D structures and materials with specialised patterns and properties. In the realm of tissue engineering and regenerative medicine (TERM), important progress has been accomplished; now, several state-of-the-art techniques are used to produce porous scaffolds for organ or tissue regeneration to be suited for tissue technology. Natural biopolymeric materials are often better suited for designing and manufacturing healing equipment than temporary implants and tissue regeneration materials owing to its appropriate properties and biocompatibility. The review focuses on the additive manufacturing of biopolymers with significant changes, advancements, trends, and developments in regenerative medicine and tissue engineering with potential applications.

scholarly journals 2,2’4,4’-Tetrabromodiphenyl Ether (PBDE-47) Modulates the Intracellular miRNA Profile, sEV Biogenesis and Their miRNA Cargo Exacerbating the LPS-Induced Pro-Inflammatory Response in THP-1 Macrophages

2021 ◽  
Vol 12 ◽  
Author(s):  
Valeria Longo ◽  
Alessandra Longo ◽  
Giorgia Adamo ◽  
Antonino Fiannaca ◽  
Sabrina Picciotto ◽  
...  
Keyword(s):  
Immune Response ◽  
Inflammatory Response ◽  
Innate Immune Response ◽  
De Novo ◽  
In Silico Analysis ◽  
Innate Immune ◽  
Macrophage Cell ◽  
Intracellular Expression ◽  
Different Levels ◽  
Silico Analysis

The 2,2’4,4’-tetrabromodiphenyl ether (PBDE-47) is one of the most prominent PBDE congeners detected in the environment and in animal and human tissues. Animal model experiments suggested the occurrence of PBDE-induced immunotoxicity leading to different outcomes and recently we demonstrated that this substance can impair macrophage and basophil activities. In this manuscript, we decided to further examine the effects induced by PBDE-47 treatment on innate immune response by looking at the intracellular expression profile of miRNAs as well as the biogenesis, cargo content and activity of human M(LPS) macrophage cell-derived small extracellular vesicles (sEVs). Microarray and in silico analysis demonstrated that PBDE-47 can induce some epigenetic effects in M(LPS) THP-1 cells modulating the expression of a set of intracellular miRNAs involved in biological pathways regulating the expression of estrogen-mediated signaling and immune responses with particular reference to M1/M2 differentiation. In addition to the cell-intrinsic modulation of intracellular miRNAs, we demonstrated that PBDE-47 could also interfere with the biogenesis of sEVs increasing their number and selecting a de novo population of sEVs. Moreover, PBDE-47 induced the overload of specific immune related miRNAs in PBDE-47 derived sEVs. Finally, culture experiments with naïve M(LPS) macrophages demonstrated that purified PBDE-47 derived sEVs can modulate macrophage immune response exacerbating the LPS-induced pro-inflammatory response inducing the overexpression of the IL-6 and the MMP9 genes. Data from this study demonstrated that PBDE-47 can perturb the innate immune response at different levels modulating the intracellular expression of miRNAs but also interfering with the biogenesis, cargo content and functional activity of M(LPS) macrophage cell-derived sEVs.

Abstract 440: Activation of Hepatic CREBH-Insig-2a Signaling in the Triglyceride-Lowering Mechanism of R-Alpha-Lipoic Acid

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Xuedong Tong ◽  
Regis Moreau ◽  
Qiaozhu Su
Keyword(s):  
Lipoic Acid ◽  
De Novo ◽  
Therapeutic Potential ◽  
Regulatory Element ◽  
Ldl Receptor ◽  
De Novo Lipogenesis ◽  
Alpha Lipoic Acid ◽  
Very Low Density Lipoproteins ◽  
Expression Of Genes

Activation of the sterol regulatory element-binding proteins (SREBPs), a step regulated by a cluster of ER-resident proteins, Insig-1, Insig-2 and SCAP, is rate limiting in hepatic de novo lipogenesis. We previously reported that feeding R-alpha-lipoic acid (LA) to ZDF (fa/fa) rats improves severe hypertriglyceridemia and lowers abdominal fat mass by inhibiting expression of genes involved in hepatic long-chain fatty acids and triacylglycerol syntheses. In this study, we characterized a novel mechanism of action of LA that explains its triacylglycerol lowering properties. Dietary LA activates liver specific transcription factor cAMP responsive element binding protein H (CREBH), which in turn enhances transcription and translation of Insig-1 and Insig-2. Chromatin immunoprecipitation (ChIP) assay demonstrated interaction between CREBH and the promoter of Insig-2 but not Insig-1. The increased abundance of Insig-1 and Insig-2 proteins contributes to sequester SREBP-1c and SREBP-2 in the ER and prevents their translocation to the Golgi apparatus where they would become activated. As a consequence, mRNA expression of genes involved in fatty acid and cholesterol synthesis, including FASN, ACC, SCD-1, HMGCR and LDL receptor, were significantly decreased in LA-fed animals versus pair-fed controls. Concomitantly, the assembly and secretion of very-low-density lipoproteins (VLDL) by primary hepatocytes were suppressed in the LA-fed ZDF rats as indicated by the decrease in VLDL-associated apolipoprotein B and apolipoprotein E. In vitro, treating a rat McA-RH7777 hepatoma cells with LA (200 micromole) activated CREBH, induced expression of Insig-1 and Insig-2, and hindered the palmitic acid-induced synthesis of triacylglycerol. This study provides new mechanistic insight into the triacylglycerol lowering properties of LA and supports the therapeutic potential of LA against hypertriglyceridemia.

scholarly journals Sub-Chronic Microcystin-LR Liver Toxicity in Preexisting Diet-Induced Nonalcoholic Steatohepatitis in Rats

Toxins ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 398 ◽  
Author(s):  
Tarana Arman ◽  
Katherine D. Lynch ◽  
Michelle L. Montonye ◽  
Michael Goedken ◽  
John D. Clarke
Keyword(s):  
Nonalcoholic Steatohepatitis ◽  
Liver Toxicity ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Sprague Dawley ◽  
Toxicant Exposure ◽  
Expression Of Genes ◽  
Sprague Dawley Rats ◽  
Progressive Liver Disease ◽  
Acid Esterification

Microcystin-LR (MCLR) is a hepatotoxic cyanotoxin reported to cause a phenotype similar to nonalcoholic steatohepatitis (NASH). NASH is a common progressive liver disease that advances in severity due to exogenous stressors such as poor diet and toxicant exposure. Our objective was to determine how sub-chronic MCLR toxicity affects preexisting diet-induced NASH. Sprague-Dawley rats were fed one of three diets for 10 weeks: control, methionine and choline deficient (MCD), or high fat/high cholesterol (HFHC). After six weeks of diet, animals received vehicle, 10 µg/kg, or 30 µg/kg MCLR via intraperitoneal injection every other day for the final 4 weeks. Incidence and severity scoring of histopathology endpoints suggested that MCLR toxicity drove NASH to a less fatty and more fibrotic state. In general, expression of genes involved in de novo lipogenesis and fatty acid esterification were altered in favor of decreased steatosis. The higher MCLR dose increased expression of genes involved in fibrosis and inflammation in the control and HFHC groups. These data suggest MCLR toxicity in the context of preexisting NASH may drive the liver to a more severe phenotype that resembles burnt-out NASH.

scholarly journals Regular exercise potentiates energetically expensive hepatic de novo lipogenesis during early weight regain

2019 ◽  
Vol 317 (5) ◽  
pp. R684-R695
Author(s):  
David M. Presby ◽  
L. Allyson Checkley ◽  
Matthew R. Jackman ◽  
Janine A. Higgins ◽  
Kenneth L. Jones ◽  
...  
Keyword(s):  
Weight Loss ◽  
Energy Expenditure ◽  
De Novo ◽  
Energy Gap ◽  
Cholesterol Biosynthesis ◽  
Density Lipoprotein ◽  
De Novo Lipogenesis ◽  
Positive Energy ◽  
Hepatic Expression ◽  
Expression Of Genes

Exercise is a potent facilitator of long-term weight loss maintenance (WLM), whereby it decreases appetite and increases energy expenditure beyond the cost of the exercise bout. We have previously shown that exercise may amplify energy expenditure through energetically expensive nutrient deposition. Therefore, we investigated the effect of exercise on hepatic de novo lipogenesis (DNL) during WLM and relapse to obesity. Obese rats were calorically restricted with (EX) or without (SED) treadmill exercise (1 h/day, 6 days/wk, 15 m/min) to induce and maintain weight loss. After 6 wk of WLM, subsets of WLM-SED and WLM-EX rats were allowed ad libitum access to food for 1 day to promote relapse (REL). An energy gap-matched group of sedentary, relapsing rats (REL-GM) were provided a diet matched to the positive energy imbalance of the REL-EX rats. During relapse, exercise increased enrichment of hepatic DN-derived lipids and induced hepatic molecular adaptations favoring DNL compared with the gap-matched controls. In the liver, compared with both REL-SED and REL-GM rats, REL-EX rats had lower hepatic expression of genes required for cholesterol biosynthesis; greater hepatic expression of genes that mediate very low-density lipoprotein synthesis and secretion; and greater mRNA expression of Cyp27a1, which encodes an enzyme involved in the biosynthesis of bile acids. Altogether, these data provide compelling evidence that the liver has an active role in exercise-mediated potentiation of energy expenditure during early relapse.

scholarly journals PDGF-AB and 5-Azacytidine induce conversion of somatic cells into tissue-regenerative multipotent stem cells

2016 ◽  
Vol 113 (16) ◽  
pp. E2306-E2315 ◽  
Author(s):  
Vashe Chandrakanthan ◽  
Avani Yeola ◽  
Jair C. Kwan ◽  
Rema A. Oliver ◽  
Qiao Qiao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factor ◽  
Tissue Regeneration ◽  
Somatic Cells ◽  
Dependent Manner ◽  
Cell Plasticity ◽  
Differentiation Potential ◽  
Multipotent Stem Cells ◽  
Differentiated Cells

Current approaches in tissue engineering are geared toward generating tissue-specific stem cells. Given the complexity and heterogeneity of tissues, this approach has its limitations. An alternate approach is to induce terminally differentiated cells to dedifferentiate into multipotent proliferative cells with the capacity to regenerate all components of a damaged tissue, a phenomenon used by salamanders to regenerate limbs. 5-Azacytidine (AZA) is a nucleoside analog that is used to treat preleukemic and leukemic blood disorders. AZA is also known to induce cell plasticity. We hypothesized that AZA-induced cell plasticity occurs via a transient multipotent cell state and that concomitant exposure to a receptive growth factor might result in the expansion of a plastic and proliferative population of cells. To this end, we treated lineage-committed cells with AZA and screened a number of different growth factors with known activity in mesenchyme-derived tissues. Here, we report that transient treatment with AZA in combination with platelet-derived growth factor–AB converts primary somatic cells into tissue-regenerative multipotent stem (iMS) cells. iMS cells possess a distinct transcriptome, are immunosuppressive, and demonstrate long-term self-renewal, serial clonogenicity, and multigerm layer differentiation potential. Importantly, unlike mesenchymal stem cells, iMS cells contribute directly to in vivo tissue regeneration in a context-dependent manner and, unlike embryonic or pluripotent stem cells, do not form teratomas. Taken together, this vector-free method of generating iMS cells from primary terminally differentiated cells has significant scope for application in tissue regeneration.

Synthesis and characterization of a photocrosslinkable chitosan–gelatin hydrogel aimed for tissue regeneration

RSC Advances ◽  
2015 ◽  
Vol 5 (78) ◽  
pp. 63478-63488 ◽  
Author(s):  
Sofia M. Saraiva ◽  
Sónia P. Miguel ◽  
Maximiano P. Ribeiro ◽  
Paula Coutinho ◽  
Ilídio J. Correia
Keyword(s):  
Tissue Engineering ◽  
Regenerative Medicine ◽  
Tissue Regeneration ◽  
Synthesis And Characterization ◽  
Native Structure ◽  
Engineering Applications ◽  
Gelatin Hydrogel

In the area of regenerative medicine different approaches have been studied to restore the native structure of damaged tissues. Herein, the suitability of a photocrosslinkable hydrogel for tissue engineering applications was studied.

scholarly journals The Purine Efflux Pump PbuE in Bacillus subtilis Modulates Expression of the PurR and G-Box (XptR) Regulons by Adjusting the Purine Base Pool Size

2005 ◽  
Vol 187 (2) ◽  
pp. 791-794 ◽  
Author(s):  
Per Nygaard ◽  
Hans H. Saxild
Keyword(s):  
Bacillus Subtilis ◽  
De Novo ◽  
Efflux Pump ◽  
Purine Base ◽  
Purine Bases ◽  
Purine Analogs ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Transcriptional Fusions

ABSTRACT In Bacillus subtilis, the expression of genes encoding enzymes and other proteins involved in purine de novo synthesis and salvage is affected by purine bases and phosphoribosylpyrophosphate (PRPP). The transcription of the genes belonging to the PurR regulon is negatively regulated by the PurR protein and PRPP. The expression of the genes belonging to the G-box (XptR) regulon, including the pbuE gene, is negatively regulated by a riboswitch-controlled transcription termination mechanism. The G-box regulon effector molecules are hypoxanthine and guanine. pbuE encodes a purine base efflux pump and is now recognized as belonging to a third purine regulon. The expression of the pbuE gene is positively regulated by a riboswitch that recognizes adenine. Here we show that the expression of pbuE′-lacZ transcriptional fusions are induced by adenine to the highest extent in mutants which do not express a functional PbuE pump. In a mutant defective in the metabolism of adenine, the ade apt mutant, we found a high intracellular level of adenine and constitutive high levels of PbuE. A growth test using a purine auxotroph provided further evidence for the role of PbuE in lowering the intracellular concentration of purine bases, including adenine. Purine analogs also affect the expression of pbuE, which might be of importance for the protection against toxic analogs. In a mutant that overexpresses PbuE, the expression of genes belonging to the PurR regulon was increased. Our findings provide further evidence for important functions of the PbuE protein, such as acting as a pump that lowers the purine base pool and affects the expression of the G-box and PurR regulons, including pbuE itself, and as a pump involved in protection against toxic purine base analogs.

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