scholarly journals Avian Stress-Related Transcriptome and Selenotranscriptome: Role during Exposure to Heavy Metals and Heat Stress

Antioxidants ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 216 ◽  
Author(s):  
Isidoros Seremelis ◽  
Georgios P. Danezis ◽  
Athanasios C. Pappas ◽  
Evangelos Zoidis ◽  
Kostas Fegeros
Keyword(s):  
Heavy Metals ◽  
Heat Stress ◽  
Antioxidant Status ◽  
Molecular Mechanisms ◽  
Mrna Levels ◽  
Stress Increase ◽  
The Past ◽  
Antioxidant Proteins ◽  
Inflammatory Proteins ◽  
Molecular Effects

Selenium, through incorporation into selenoproteins, is one of the key elements of the antioxidant system. Over the past few years there has been increased interest in exploring those molecular mechanisms in chicken, responsible for the development of this protection system. In more detail, Cd/Pb poisoning and heat stress increase oxidation, mRNA levels of inflammatory proteins, and apoptotic proteins. Selenium seems to enhance the antioxidant status and alleviates these effects via upregulation of antioxidant proteins and other molecular effects. In this review, we analyze avian transcriptome key elements with particular emphasis on interactions with heavy metals and on relation to heat stress.

Novel Findings of Anti-cancer Property of Propofol

2018 ◽  
Vol 18 (2) ◽  
pp. 156-165 ◽  
Author(s):  
Jiaqiang Wang ◽  
Chien-shan Cheng ◽  
Yan Lu ◽  
Xiaowei Ding ◽  
Minmin Zhu ◽  
...  
Keyword(s):  
General Anesthesia ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Intravenous Anesthetic ◽  
The Past ◽  
Anti Cancer ◽  
Underlying Mechanisms ◽  
Recent Attention

Background: Propofol, a widely used intravenous anesthetic agent, is traditionally applied for sedation and general anesthesia. Explanation: Recent attention has been drawn to explore the effect and mechanisms of propofol against cancer progression in vitro and in vivo. Specifically, the proliferation-inhibiting and apoptosis-inducing properties of propofol in cancer have been studied. However, the underlying mechanisms remain unclear. Conclusion: This review focused on the findings within the past ten years and aimed to provide a general overview of propofol's malignance-modulating properties and the potential molecular mechanisms.

Understanding Molecular Process and Chemotherapeutics for the Management of Breast Cancer.

2020 ◽  
Vol 14 ◽  
Author(s):  
Abhishek Kumar ◽  
Neeraj Masand ◽  
Vaishali M. Patil
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Molecular Targets ◽  
Molecular Classification ◽  
Neoplastic Disease ◽  
Molecular Process ◽  
The Past ◽  
Anti Cancer ◽  
Molecular Etiology ◽  
Near Future

Abstract: Breast cancer is the most common and highly heterogeneous neoplastic disease comprised of several subtypes with distinct molecular etiology and clinical behaviours. The mortality observed over the past few decades and the failure in eradicating the disease is due to the lack of specific etiology, molecular mechanisms involved in initiation and progression of breast cancer. Understanding of the molecular classes of breast cancer may also lead to new biological insights and eventually to better therapies. The promising therapeutic targets and novel anti-cancer approaches emerging from these molecular targets that could be applied clinically in the near future are being highlighted. In addition, this review discusses some of the details of current molecular classification and available chemotherapeutics

scholarly journals Protective Effect of Psoralea corylifolia L. Seed Extract against Palmitate-Induced Neuronal Apoptosis in PC12 Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Yunkyoung Lee ◽  
Hee-Sook Jun ◽  
Yoon Sin Oh
Keyword(s):  
Pc12 Cells ◽  
Molecular Mechanisms ◽  
Neuronal Cell ◽  
Marker Genes ◽  
Heme Oxygenase 1 ◽  
Mrna Levels ◽  
Protective Effects ◽  
Psoralea Corylifolia ◽  
Antioxidant Genes ◽  
Bax Protein

The extract of Psoralea corylifolia seeds (PCE) has been widely used as a herbal medicine because of its beneficial effect on human health. In this study, we investigated the protective effects and molecular mechanisms of PCE on palmitate- (PA-) induced toxicity in PC12 cells, a neuron-like cell line. PCE significantly increased cell viability in PA-treated PC12 cells and showed antiapoptotic effects, as evidenced by decreased expression of cleaved caspase-3, cleaved poly(ADP-ribose) polymerase, and bax protein as well as increased expression of bcl-2 protein. In addition, PCE treatment reduced PA-induced reactive oxygen species production and upregulated mRNA levels of antioxidant genes such as nuclear factor (erythroid-derived 2)-like 2 and heme oxygenase 1. Moreover, PCE treatment recovered the expression of autophagy marker genes such as beclin-1 and p62, which was decreased by PA treatment. Treatment with isopsoralen, one of the major components of PCE extract, also recovered the expression of autophagy marker genes and reduced PA-induced apoptosis. In conclusion, PCE exerts protective effects against lipotoxicity via its antioxidant function, and this effect is mediated by activation of autophagy. PCE might be a potential pharmacological agent to protect against neuronal cell injury caused by oxidative stress or lipotoxicity.

scholarly journals Ketamine—50 years in use: from anesthesia to rapid antidepressant effects and neurobiological mechanisms

2021 ◽  
Vol 73 (2) ◽  
pp. 323-345
Author(s):  
Samuel Kohtala
Keyword(s):  
Traumatic Stress ◽  
Molecular Mechanisms ◽  
Post Traumatic Stress ◽  
Active Metabolites ◽  
The Past ◽  
Antidepressant Effects ◽  
Post Traumatic ◽  
Pharmacologically Active ◽  
Dose Dependent ◽  
Different Doses

AbstractOver the past 50 years, ketamine has solidified its position in both human and veterinary medicine as an important anesthetic with many uses. More recently, ketamine has been studied and used for several new indications, ranging from chronic pain to drug addiction and post-traumatic stress disorder. The discovery of the rapid-acting antidepressant effects of ketamine has resulted in a surge of interest towards understanding the precise mechanisms driving its effects. Indeed, ketamine may have had the largest impact for advancements in the research and treatment of psychiatric disorders in the past few decades. While intense research efforts have been aimed towards uncovering the molecular targets underlying ketamine’s effects in treating depression, the underlying neurobiological mechanisms remain elusive. These efforts are made more difficult by ketamine’s complex dose-dependent effects on molecular mechanisms, multiple pharmacologically active metabolites, and a mechanism of action associated with the facilitation of synaptic plasticity. This review aims to provide a brief overview of the different uses of ketamine, with an emphasis on examining ketamine’s rapid antidepressant effects spanning molecular, cellular, and network levels. Another focus of the review is to offer a perspective on studies related to the different doses of ketamine used in antidepressant research. Finally, the review discusses some of the latest hypotheses concerning ketamine’s action.

scholarly journals DNA Methylation Profiles of Tph1A and BDNF in Gut and Brain of L. Rhamnosus-Treated Zebrafish

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 142
Author(s):  
Mariella Cuomo ◽  
Luca Borrelli ◽  
Rosa Della Monica ◽  
Lorena Coretti ◽  
Giulia De Riso ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Molecular Mechanisms ◽  
The Past ◽  
Targeted Analysis ◽  
Lack Of Information ◽  
High Resolution Power ◽  
Resolution Level ◽  
Health And Disease ◽  
High Doses ◽  
The Brain

The bidirectional microbiota–gut–brain axis has raised increasing interest over the past years in the context of health and disease, but there is a lack of information on molecular mechanisms underlying this connection. We hypothesized that change in microbiota composition may affect brain epigenetics leading to long-lasting effects on specific brain gene regulation. To test this hypothesis, we used Zebrafish (Danio Rerio) as a model system. As previously shown, treatment with high doses of probiotics can modulate behavior in Zebrafish, causing significant changes in the expression of some brain-relevant genes, such as BDNF and Tph1A. Using an ultra-deep targeted analysis, we investigated the methylation state of the BDNF and Tph1A promoter region in the brain and gut of probiotic-treated and untreated Zebrafishes. Thanks to the high resolution power of our analysis, we evaluated cell-to-cell methylation differences. At this resolution level, we found slight DNA methylation changes in probiotic-treated samples, likely related to a subgroup of brain and gut cells, and that specific DNA methylation signatures significantly correlated with specific behavioral scores.

scholarly journals Differential Morpho-Physiological and Transcriptomic Responses to Heat Stress in Two Blueberry Species

2021 ◽  
Vol 22 (5) ◽  
pp. 2481
Author(s):  
Jodi Callwood ◽  
Kalpalatha Melmaiee ◽  
Krishnanand P. Kulkarni ◽  
Amaranatha R. Vennapusa ◽  
Diarra Aicha ◽  
...  
Keyword(s):  
Heat Stress ◽  
Molecular Mechanisms ◽  
Stomatal Closure ◽  
Enrichment Analysis ◽  
Leaf Size ◽  
Vaccinium Corymbosum ◽  
Climatic Conditions ◽  
Differentially Expressed ◽  
Transcriptomic Changes ◽  
Go Terms

Blueberries (Vaccinium spp.) are highly vulnerable to changing climatic conditions, especially increasing temperatures. To gain insight into mechanisms underpinning the response to heat stress, two blueberry species were subjected to heat stress for 6 and 9 h at 45 °C, and leaf samples were used to study the morpho-physiological and transcriptomic changes. As compared with Vaccinium corymbosum, Vaccinium darrowii exhibited thermal stress adaptation features such as small leaf size, parallel leaf orientation, waxy leaf coating, increased stomatal surface area, and stomatal closure. RNAseq analysis yielded ~135 million reads and identified 8305 differentially expressed genes (DEGs) during heat stress against the control samples. In V. corymbosum, 2861 and 4565 genes were differentially expressed at 6 and 9 h of heat stress, whereas in V. darrowii, 2516 and 3072 DEGs were differentially expressed at 6 and 9 h, respectively. Among the pathways, the protein processing in the endoplasmic reticulum (ER) was the highly enriched pathway in both the species: however, certain metabolic, fatty acid, photosynthesis-related, peroxisomal, and circadian rhythm pathways were enriched differently among the species. KEGG enrichment analysis of the DEGs revealed important biosynthesis and metabolic pathways crucial in response to heat stress. The GO terms enriched in both the species under heat stress were similar, but more DEGs were enriched for GO terms in V. darrowii than the V. corymbosum. Together, these results elucidate the differential response of morpho-physiological and molecular mechanisms used by both the blueberry species under heat stress, and help in understanding the complex mechanisms involved in heat stress tolerance.

scholarly journals Molecular Mechanisms of ZC3H12C/Reg-3 Biological Activity and Its Involvement in Psoriasis Pathology

2021 ◽  
Vol 22 (14) ◽  
pp. 7311
Author(s):  
Mateusz Wawro ◽  
Jakub Kochan ◽  
Weronika Sowinska ◽  
Aleksandra Solecka ◽  
Karolina Wawro ◽  
...  
Keyword(s):  
Family Member ◽  
Cellular Localization ◽  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Association Studies ◽  
Psoriasis Patient ◽  
Genome Wide Association Studies ◽  
Mrna Levels ◽  
Transcript Levels

The members of the ZC3H12/MCPIP/Regnase family of RNases have emerged as important regulators of inflammation. In contrast to Regnase-1, -2 and -4, a thorough characterization of Regnase-3 (Reg-3) has not yet been explored. Here we demonstrate that Reg-3 differs from other family members in terms of NYN/PIN domain features, cellular localization pattern and substrate specificity. Together with Reg-1, the most comprehensively characterized family member, Reg-3 shared IL-6, IER-3 and Reg-1 mRNAs, but not IL-1β mRNA, as substrates. In addition, Reg-3 was found to be the only family member which regulates transcript levels of TNF, a cytokine implicated in chronic inflammatory diseases including psoriasis. Previous meta-analysis of genome-wide association studies revealed Reg-3 to be among new psoriasis susceptibility loci. Here we demonstrate that Reg-3 transcript levels are increased in psoriasis patient skin tissue and in an experimental model of psoriasis, supporting the immunomodulatory role of Reg-3 in psoriasis, possibly through degradation of mRNA for TNF and other factors such as Reg-1. On the other hand, Reg-1 was found to destabilize Reg-3 transcripts, suggesting reciprocal regulation between Reg-3 and Reg-1 in the skin. We found that either Reg-1 or Reg-3 were expressed in human keratinocytes in vitro. However, in contrast to robustly upregulated Reg-1 mRNA levels, Reg-3 expression was not affected in the epidermis of psoriasis patients. Taken together, these data suggest that epidermal levels of Reg-3 are negatively regulated by Reg-1 in psoriasis, and that Reg-1 and Reg-3 are both involved in psoriasis pathophysiology through controlling, at least in part different transcripts.

scholarly journals In Ovo Injection of GABA Can Help Body Weight Gain at Hatch, Increase Chick Weight to Egg Weight Ratio, and Improve Broiler Heat Resistance

Animals ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1364
Author(s):  
Chris Major Ncho ◽  
Akshat Goel ◽  
Chae-Mi Jeong ◽  
Mohamed Youssouf ◽  
Yang-Ho Choi
Keyword(s):  
Antioxidant Capacity ◽  
Total Antioxidant Capacity ◽  
Antioxidant Status ◽  
Body Weight Gain ◽  
Weight Ratio ◽  
The Other ◽  
Mrna Levels ◽  
In Ovo ◽  
Total Antioxidant ◽  
In Ovo Injection

The aim of this study was to explore the outcomes of an in ovo GABA injection in broilers challenged with HS. In Experiment 1, 210 Arbor Acres eggs were allocated to five treatments: no-injection, and in ovo injection of 0.6 mL of 0%, 5%, 10%, or 20% of GABA. Hatchling weight and CWEWR were significantly increased in the 5% GABA group. In ovo, injection of 10% GABA solution caused a significant decrease in plasma cholesterol and increased plasma total antioxidant capacity of hatchlings. Experiment 2 was conducted with 126 fertile Arbor Acres eggs distributed into one of two groups. At 17.5 days of incubation, one received no injection, and the other was fed 0.6 mL of 10% GABA. On day 10, one subgroup (4 replicates * 3 birds) from each treatment was submitted to HS (38 ± 1 °C for 3 h) while the other was kept at a thermoneutral temperature (29 ± 1 °C). An in ovo injection of GABA significantly increased total antioxidant capacity, but reduced malondialdehyde levels, hepatic mRNA levels of HSP70, FAS, and L-FABP with HS. In conclusion, an in ovo GABA injection improves CWEWR and antioxidant status at hatch, and enhances antioxidant status while downregulating the expression of HSP70 and fatty acid metabolism-related genes in young chicks under HS.

scholarly journals Targeting fibroblast growth factor receptors to combat aggressive ependymoma

2021 ◽  
Author(s):  
Daniela Lötsch ◽  
Dominik Kirchhofer ◽  
Bernhard Englinger ◽  
Li Jiang ◽  
Konstantin Okonechnikov ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Molecular Mechanisms ◽  
Radial Glia ◽  
Growth Factor Receptors ◽  
Dominant Negative ◽  
Mrna Levels ◽  
Fibroblast Growth ◽  
Cell Models ◽  
Fibroblast Growth Factor Receptors

AbstractEpendymomas (EPN) are central nervous system tumors comprising both aggressive and more benign molecular subtypes. However, therapy of the high-risk subtypes posterior fossa group A (PF-A) and supratentorial RELA-fusion positive (ST-RELA) is limited to gross total resection and radiotherapy, as effective systemic treatment concepts are still lacking. We have recently described fibroblast growth factor receptors 1 and 3 (FGFR1/FGFR3) as oncogenic drivers of EPN. However, the underlying molecular mechanisms and their potential as therapeutic targets have not yet been investigated in detail. Making use of transcriptomic data across 467 EPN tissues, we found that FGFR1 and FGFR3 were both widely expressed across all molecular groups. FGFR3 mRNA levels were enriched in ST-RELA showing the highest expression among EPN as well as other brain tumors. We further identified high expression levels of fibroblast growth factor 1 and 2 (FGF1, FGF2) across all EPN subtypes while FGF9 was elevated in ST-EPN. Interrogation of our EPN single-cell RNA-sequencing data revealed that FGFR3 was further enriched in cycling and progenitor-like cell populations. Corroboratively, we found FGFR3 to be predominantly expressed in radial glia cells in both mouse embryonal and human brain datasets. Moreover, we detected alternative splicing of the FGFR1/3-IIIc variant, which is known to enhance ligand affinity and FGFR signaling. Dominant-negative interruption of FGFR1/3 activation in PF-A and ST-RELA cell models demonstrated inhibition of key oncogenic pathways leading to reduced cell growth and stem cell characteristics. To explore the feasibility of therapeutically targeting FGFR, we tested a panel of FGFR inhibitors in 12 patient-derived EPN cell models revealing sensitivity in the low-micromolar to nano-molar range. Finally, we gain the first clinical evidence for the activity of the FGFR inhibitor nintedanib in the treatment of a patient with recurrent ST-RELA. Together, these preclinical and clinical data suggest FGFR inhibition as a novel and feasible approach to combat aggressive EPN.

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