scholarly journals Garlic Derived Diallyl Trisulfide in Experimental Metabolic Syndrome: Metabolic Effects and Cardioprotective Role

2020 ◽  
Vol 21 (23) ◽  
pp. 9100
Author(s):  
Jovana N. Jeremic ◽  
Vladimir Lj. Jakovljevic ◽  
Vladimir I. Zivkovic ◽  
Ivan M. Srejovic ◽  
Jovana V. Bradic ◽  
...  

This study aimed to examine the effects of diallyl trisulfide (DATS), the most potent polysulfide derived from garlic, on metabolic syndrome and myocardial function in rats with metabolic syndrome (MetS). For that purpose, we used 36 male Wistar albino rats divided into control rats, rats with MetS and MetS rats treated with 40 mg/kg of DATS every second day for 3 weeks. In the first part, we studied the impact of DATS on MetS control and found that DATS significantly raised H2S, decreased homocysteine and glucose levels and enhanced lipid and antioxidative, while reducing prooxidative parameters. Additionally, this polysulfide improved cardiac function. In the second part, we investigated the impact of DATS on ex vivo induced ischemia/reperfusion (I/R) heart injury and found that DATS consumption significantly improved cardiodynamic parameters and prevented oxidative and histo-architectural variation in the heart. In addition, DATS significantly increased relative gene expression of eNOS, SOD-1 and -2, Bcl-2 and decreased relative gene expression of NF-κB, IL-17A, Bax, and caspases-3 and -9. Taken together, the data show that DATS can effectively mitigate MetS and have protective effects against ex vivo induced myocardial I/R injury in MetS rat.

Forests ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 631
Author(s):  
Jian Qin ◽  
Xiliang Yue ◽  
Xulan Shang ◽  
Shengzuo Fang

Cyclocarya paliurus (Batalin) Iljinsk. is a multiple function tree species distributed in subtropical areas, and its leaves have been used in medicine and nutraceutical foods in China. However, little information on the effects of nitrogen (N) forms and ratios on growth and secondary metabolite accumulation is available for C. paliurus. The impact of five NO3−/NH4+ ratios on biomass production, triterpenoid accumulation and related gene expression in C. paliurus seedlings was evaluated at the middle N nutrition supply. Significant differences in seedling growth, triterpenoid accumulation and relative gene expression were observed among the different NO3−/NH4+ ratio treatments. The highest triterpenoid content was achieved in a sole NO3− or NH4+ nutrition, while the mixed N nutrition with equal ratio of NO3− to NH4+ produced the highest biomass production in the seedlings. However, the highest triterpenoid accumulation was achieved at the treatment with the ratio of NO3−/NH4+ = 2.33. Therefore, the mixed N nutrition of NO3− and NH4+ was beneficial to the triterpenoid accumulation per plant. The relative expression of seven genes that are involved in triterpenoid biosynthesis were all up-regulated under the sole NH4+ or NO3− nutrition conditions, and significantly positive correlations between triterpenoid content and relative gene expression of key enzymes were detected in the leaves. Our results indicated that NO3− is the N nutrition preferred by C. paliurus, but the mixture of NO3− and NH4+ at an appropriate ratio would improve the leaf triterpenoid yield per area.


2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 155-157
Author(s):  
Q Wang ◽  
A Wilson

Abstract Background Azathioprine (AZA), an immunosuppressant, has classically been used to treat patients with inflammatory bowel disease (IBD). AZA inhibits purine synthesis, and its metabolism occurs via a pathway involving thiopurine methyltransferase (TPMT). While standard TPMT genetic screening is conducted for IBD patients initiating AZA treatment to minimize adverse drug effects (ADE), a majority of patients experiencing ADE have wildtype TPMT. Another gene, NUDT15, has been found to be associated with AZA-related myelotoxicity Aims In this study we report two novel variants in NUDT15 and aim to evaluate the impact of NUDT15 variation on its gene expression. We hypothesize that the mutations found within novel NUDT15 variant are detrimental either to the gene’s expression levels or its translation process, resulting in a lower amount of NUDT15 product present and hence translating to AZA-related myelotoxicity observed clinically. Methods IBD patients experiencing AZA-related myelotoxicity were recruited for this study. Patients were then genotyped and the NUDT15 variants were replicated through site-directed mutagenesis. The NUDT15 variants were subsequently transformed into mammalian cell lines then E. coli cells. DNA products were isolated, and transcription levels were assessed through RT-PCR. Results Patient cohort consisted of 27 AZA-exposed IBD patients who developed myelotoxicity despite their TPMT wildtype genotype. Two novel NUDT15 variants were found. The mutation in one of the variants was placed in 3’ UTR, and hence further research was not pursued. Further analysis was conducted for the variant with mutation in coding region. RT-PCR was conducted to assess and compare gene transcription levels between wildtype and variant NUDT15. Wildtype NUDT15 had a relative gene expression level of 0.8x107, whereas variant NUDT15’s relative gene expression level was at 1.1x107. The two groups were not significantly different in terms of gene expression. Conclusions Contrary to our initial hypothesis, it appears that the mutation in the start codon for variant NUDT15 gene does not significantly impact its gene expression as compared to the wildtype gene. We are currently pursuing protein expression analysis studies to assess for translational deficits possibly present in the novel NUDT15 variant. Funding Agencies SRTP - Schulich School of Medicine


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Federico Tinarelli ◽  
Elena Ivanova ◽  
Ilaria Colombi ◽  
Erica Barini ◽  
Edoardo Balzani ◽  
...  

Abstract Background DNA methylation has emerged as an important epigenetic regulator of brain processes, including circadian rhythms. However, how DNA methylation intervenes between environmental signals, such as light entrainment, and the transcriptional and translational molecular mechanisms of the cellular clock is currently unknown. Here, we studied the after-hours mice, which have a point mutation in the Fbxl3 gene and a lengthened circadian period. Methods In this study, we used a combination of in vivo, ex vivo and in vitro approaches. We measured retinal responses in Afh animals and we have run reduced representation bisulphite sequencing (RRBS), pyrosequencing and gene expression analysis in a variety of brain tissues ex vivo. In vitro, we used primary neuronal cultures combined to micro electrode array (MEA) technology and gene expression. Results We observed functional impairments in mutant neuronal networks, and a reduction in the retinal responses to light-dependent stimuli. We detected abnormalities in the expression of photoreceptive melanopsin (OPN4). Furthermore, we identified alterations in the DNA methylation pathways throughout the retinohypothalamic tract terminals and links between the transcription factor Rev-Erbα and Fbxl3. Conclusions The results of this study, primarily represent a contribution towards an understanding of electrophysiological and molecular phenotypic responses to external stimuli in the Afh model. Moreover, as DNA methylation has recently emerged as a new regulator of neuronal networks with important consequences for circadian behaviour, we discuss the impact of the Afh mutation on the epigenetic landscape of circadian biology.


2021 ◽  
Vol 11 (15) ◽  
pp. 7144
Author(s):  
Muriel C. Bischof ◽  
Sonja Häckel ◽  
Andrea Oberli ◽  
Andreas S. Croft ◽  
Katharina A. C. Oswald ◽  
...  

Increasing evidence implicates intervertebral disc (IVD) degeneration as a major contributor to low back pain. In addition to a series of pathogenic processes, degenerated IVDs become vascularized in contrast to healthy IVDs. In this context, angiopoietin (Ang) plays a crucial role and is involved in cytokine recruitment, and anabolic and catabolic reactions within the extracellular matrix (ECM). Over the last decade, a progenitor cell population has been described in the nucleus pulposus (NP) of the IVD to be positive for the Tie2 marker (also known as Ang-1 receptor). In this study, we investigated the influence of Ang-1 and Ang-2 on human NP cell (Tie2+, Tie2- or mixed) populations isolated from trauma patients during 7 days in normoxia (21% O2) or hypoxia (≤ 5% O2). At the end of the process, the proliferation and metabolic activity of the NP cells were analyzed. Additionally, the relative gene expression of NP-related markers was evaluated. NP cells showed a higher proliferation depending on the Ang treatment. Moreover, the study revealed higher NP cell metabolism when cultured in hypoxia. Additionally, the relative gene expression followed, with an increase linked to the oxygen level and Ang concentration. Our study comparing different NP cell populations may be the start of new approaches for the treatment of IVD degeneration.


Author(s):  
D.L. Silva ◽  
B.R. Carvalho ◽  
H.C. Ferreira Júnior ◽  
H.C. Oliveira ◽  
C.R. Ferreira ◽  
...  

Nutrients ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 1920 ◽  
Author(s):  
Carla Busquets-Cortés ◽  
Xavier Capó ◽  
Emma Argelich ◽  
Miguel Ferrer ◽  
David Mateos ◽  
...  

Reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) can exert opposed effects depending on the dosage: low levels can be involved in signalling and adaptive processes, while higher levels can exert deleterious effects in cells and tissues. Our aim was to emulate a chronic ex vivo oxidative stress situation through a 2 h exposure of immune cells to sustained H2O2 produced by glucose oxidase (GOX), at high or low production rate, in order to determine dissimilar responses of peripheral blood mononuclear cells (PBMCs) and neutrophils on ROS and cytokine production, and mitochondrial dynamics-related proteins, pro/anti-inflammatory and anti-oxidant gene expression. Immune cells were obtained from subjects with metabolic syndrome. H2O2 at low concentrations can trigger a transient anti-inflammatory adiponectin secretion and reduced gene expression of toll-like receptors (TLRs) in PBMCs but may act as a stimulator of proinflammatory genes (IL6, IL8) and mitochondrial dynamics-related proteins (Mtf2, NRF2, Tfam). H2O2 at a high concentration enhances the expression of pro-inflammatory genes (TLR2 and IL1β) and diminishes the expression of mitochondrial dynamics-related proteins (Mtf1, Tfam) and antioxidant enzymes (Cu/Zn SOD) in PBMCs. The GOX treatments produce dissimilar changes in immune cells: Neutrophils were more resistant to H2O2 effects and exhibited a more constant response in terms of gene expression than PBMCs. We observe emerging roles of H2O2 in mitochondrial dynamics and redox and inflammation processes in immune cells.


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