scholarly journals Prunus persica plant endogenous peptides PpPep1 and PpPep2 cause PTI-like transcriptome reprogramming in peach and enhance resistance to Xanthomonas arboricola pv. pruni

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Laura Foix ◽  
Anna Nadal ◽  
Maja Zagorščak ◽  
Živa Ramšak ◽  
Anna Esteve-Codina ◽  
...  
Keyword(s):  
Topical Application ◽  
Prunus Persica ◽  
Ex Vivo ◽  
Background Knowledge ◽  
Knowledge Network ◽  
Plant Responses ◽  
Protective Effects ◽  
Transcriptomic Response ◽  
Xanthomonas Arboricola

Abstract Background Rosaceae species are economically highly relevant crops. Their cultivation systems are constrained by phytopathogens causing severe losses. Plants respond to invading pathogens through signaling mechanisms, a component of which are of them being plant elicitor peptides (Peps). Exogenous application of Peps activates defense mechanisms and reduces the symptoms of pathogen infection in various pathosystems. We have previously identified the Rosaceae Peps and showed, in an ex vivo system, that their topical application efficiently enhanced resistance to the bacterial pathogen Xanthomonas arboricola pv. pruni (Xap). Results Here we demonstrate the effectiveness of Prunus persica peptides PpPep1 and PpPep2 in protecting peach plants in vivo at nanomolar doses, with 40% reduction of the symptoms following Xap massive infection. We used deep sequencing to characterize the transcriptomic response of peach plants to preventive treatment with PpPep1 and PpPep2. The two peptides induced highly similar massive transcriptomic reprogramming in the plant. One hour, 1 day and 2 days after peptide application there were changes in expression in up to 8% of peach genes. We visualized the transcriptomics dynamics in a background knowledge network and detected the minor variations between plant responses to PpPep1 and PpPep2, which might explain their slightly different protective effects. By designing a P. persica Pep background knowledge network, comparison of our data and previously published immune response datasets was possible. Conclusions Topical application of P. persica Peps mimics the PTI natural response and protects plants against massive Xap infection. This makes them good candidates for deployment of natural, targeted and environmental-friendly strategies to enhance resistance in Prunus species and prevent important biotic diseases.

Influence of estrogen on individual exercise motivation and bone protection in ovariectomized rats

2018 ◽  
Vol 52 (5) ◽  
pp. 479-489 ◽  
Author(s):  
Sebastian T Müller ◽  
Annekathrin M Keiler ◽  
Kristin Kräker ◽  
Oliver Zierau ◽  
Ricardo Bernhardt
Keyword(s):  
Bone Loss ◽  
Ex Vivo ◽  
Voluntary Exercise ◽  
Ovariectomized Rats ◽  
Protective Effects ◽  
Exercise Motivation ◽  
Running Wheel ◽  
Future Studies ◽  
Bone Protection

Bone protection and metabolism are directly linked to estrogen levels, but exercise is also considered to have bone protective effects. Reduced estrogen levels lead to a variety of disorders, for example, bone loss and reduced movement drive. The objective of this study was to investigate the effects of estrogen on individual voluntary exercise motivation and bone protection. We investigated sham operated, ovariectomized, and ovariectomized with estrogen supplemented Wistar rats (20 weeks old) either with or without access to exercise wheels. We selected an experimental approach where we could monitor the individual exercise of group-housed rats with ad libitum access to a running wheel with the help of a subcutaneous chip. In vivo and ex vivo microcomputed tomography analyses of the tibia were performed at two-week intervals from week 0 to week 6. Furthermore, tibial trabecular structure was evaluated based on histomorphometric analyses. We observed a significant bone protective effect of E2. For exercise performance, a substantially high intra-group variability was observed, especially in the E2 group. We presume that dominant behavior occurs within the group-housed rats resulting in a hierarchical access to the running wheel and a high variability of distance run. Exercise did not prevent ovariectomy-induced bone loss. However, lack of estrogen within the ovariectomized rats led to a drastically reduced activity prevented by estrogen supplementation. Our findings are important for future studies working with group-housed rats and exercise. The reason for the high intra-group variability in exercise needs to be investigated in future studies.

Aloe Metabolites Prevent LPS-Induced Sepsis and Inflammatory Response by Inhibiting Mitogen-Activated Protein Kinase Activation

2017 ◽  
Vol 45 (04) ◽  
pp. 847-861 ◽  
Author(s):  
Chia-Yang Li ◽  
Katsuhiko Suzuki ◽  
Yung-Li Hung ◽  
Meng-Syuan Yang ◽  
Chung-Ping Yu ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Aloe Vera ◽  
Peritoneal Macrophages ◽  
Mitogen Activated Protein Kinase ◽  
Protective Effects ◽  
Raw264.7 Macrophages ◽  
Mitogen Activated Protein ◽  
Anti Inflammatory

Aloe, a polyphenolic anthranoid-containing Aloe vera leaves, is a Chinese medicine and a popular dietary supplement worldwide. In in vivo situations, polyphenolic anthranoids are extensively broken down into glucuronides and sulfate metabolites by the gut and the liver. The anti-inflammatory potential of aloe metabolites has not been examined. The aim of this study was to investigate the anti-inflammatory effects of aloe metabolites from in vitro (lipopolysaccharides (LPS)-activated RAW264.7 macrophages) and ex vivo (LPS-activated peritoneal macrophages) to in vivo (LPS-induced septic mice). The production of proinflammatory cytokines (TNF-[Formula: see text] and IL-12) and NO was determined by ELISA and Griess reagents, respectively. The expression levels of iNOS and MAPKs were analyzed by Western blot. Our results showed that aloe metabolites inhibited the expression of iNOS, decreased the production of TNF-[Formula: see text], IL-12, and NO, and suppressed the phosphorylation of MAPKs by LPS-activated RAW264.7 macrophages. In addition, aloe metabolites reduced the production of NO, TNF-[Formula: see text] and IL-12 by murine peritoneal macrophages. Furthermore, aloe administration significantly reduced the NO level and exhibited protective effects against sepsis-related death in LPS-induced septic mice. These results suggest that aloe metabolites exerted anti-inflammatory effects in vivo, and that these effects were associated with the inhibition of inflammatory mediators. Therefore, aloe could be considered an effective therapeutic agent for the treatment of sepsis.

scholarly journals Reduction of cardiomyocyte S-nitrosylation by S-nitrosoglutathione reductase protects against sepsis-induced myocardial depression

2013 ◽  
Vol 304 (8) ◽  
pp. H1134-H1146 ◽  
Author(s):  
Patrick Y. Sips ◽  
Tomoya Irie ◽  
Lin Zou ◽  
Shohei Shinozaki ◽  
Michihiro Sakai ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Ex Vivo ◽  
Myocardial Dysfunction ◽  
Endotoxic Shock ◽  
Protein S ◽  
Septic Cardiomyopathy ◽  
Protective Effects ◽  
Myocardial Depression ◽  
Lps Challenge

Myocardial depression is an important contributor to morbidity and mortality in septic patients. Nitric oxide (NO) plays an important role in the development of septic cardiomyopathy, but also has protective effects. Recent evidence has indicated that NO exerts many of its downstream effects on the cardiovascular system via protein S-nitrosylation, which is negatively regulated by S-nitrosoglutathione reductase (GSNOR), an enzyme promoting denitrosylation. We tested the hypothesis that reducing cardiomyocyte S-nitrosylation by increasing GSNOR activity can improve myocardial dysfunction during sepsis. Therefore, we generated mice with a cardiomyocyte-specific overexpression of GSNOR (GSNOR-CMTg mice) and subjected them to endotoxic shock. Measurements of cardiac function in vivo and ex vivo showed that GSNOR-CMTg mice had a significantly improved cardiac function after lipopolysaccharide challenge (LPS, 50 mg/kg) compared with wild-type (WT) mice. Cardiomyocytes isolated from septic GSNOR-CMTg mice showed a corresponding improvement in contractility compared with WT cells. However, systolic Ca2+ release was similarly depressed in both genotypes after LPS, indicating that GSNOR-CMTg cardiomyocytes have increased Ca2+ sensitivity during sepsis. Parameters of inflammation were equally increased in LPS-treated hearts of both genotypes, and no compensatory changes in NO synthase expression levels were found in GSNOR-overexpressing hearts before or after LPS challenge. GSNOR overexpression however significantly reduced total cardiac protein S-nitrosylation during sepsis. Taken together, our results indicate that increasing the denitrosylation capacity of cardiomyocytes protects against sepsis-induced myocardial depression. Our findings suggest that specifically reducing protein S-nitrosylation during sepsis improves cardiac function by increasing cardiac myofilament sensitivity to Ca2+.

Exopolysaccharide from Bifidobacterium longum subsp. longum 35624™ modulates murine allergic airway responses

2018 ◽  
Vol 9 (5) ◽  
pp. 761-773 ◽  
Author(s):  
E. Schiavi ◽  
S. Plattner ◽  
N. Rodriguez-Perez ◽  
W. Barcik ◽  
R. Frei ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Bifidobacterium Longum ◽  
Immunological Tolerance ◽  
Respiratory Allergy ◽  
In Vivo Studies ◽  
Protective Effects ◽  
Protective Mechanisms ◽  
Eosinophil Recruitment

Interactions between the host and the microbiota are thought to significantly influence immunological tolerance mechanisms at mucosal sites. We recently described that the loss of an exopolysaccharide (EPS) from Bifidobacterium longum 35624™ eliminated its protective effects in colitis and respiratory allergy murine models. Our goal was to investigate the immune response to purified EPS from B. longum 35624, determine if it has protective effects within the lung and identify the protective mechanisms. Isolated EPS from B. longum 35624 cultures was used for in vitro, ex vivo and in vivo studies. Human monocyte-derived dendritic cells (MDDCs) were used to investigate in vitro immunological responses to EPS. Cytokine secretion, expression of surface markers and signalling pathways were examined. The ovalbumin (OVA) respiratory allergy murine model was used to evaluate the in vivo immunomodulatory potential of EPS. In addition, interleukin (IL)-10 knockout (KO) mice and anti-Toll-like receptor (TLR)-2 blocking antibody were used to examine the underlying protective mechanisms of intranasal EPS administration. Stimulation of human MDDCs with EPS resulted in IL-10 secretion, but not proinflammatory cytokines. IL-10 secretion was TLR-2-dependent. Eosinophil recruitment to the lungs was significantly decreased by EPS intranasal exposure, which was associated with decreased expression of the Th2-associated markers C-C motif chemokine 11 (CCL11), C-C chemokine receptor type 3 (CCR3), IL-4 and IL-13. TLR-2-mediated IL-10 secretion was shown to be required for the reduction in eosinophils and Th2 cytokines. EPS-treatment reduced eosinophil recruitment within the lung in a respiratory inflammation mouse model, which is both TLR-2 and IL-10 mediated. EPS can be considered as a novel molecule potentially reducing the severity of chronic eosinophil-related airway disorders.

scholarly journals Bile acid bio-nanoencapsulation improved drug targeted-delivery and pharmacological effects via cellular flux: 6-months diabetes preclinical study

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Armin Mooranian ◽  
Susbin Raj Wagle ◽  
Bozica Kovacevic ◽  
Ryu Takechi ◽  
John Mamo ◽  
...  
Keyword(s):  
Bile Acid ◽  
Targeted Delivery ◽  
Oral Delivery ◽  
Ex Vivo ◽  
Biological Effects ◽  
Protective Effects ◽  
Β Cells ◽  
Positive Effects ◽  
Anti Inflammatory

AbstractThe antilipidemic drug, probucol (PB), has demonstrated potential applications in Type 2 diabetes (T2D) through its protective effects on pancreatic β-cells. PB has poor solubility and bioavailability, and despite attempts to improve its oral delivery, none has shown dramatic improvements in absorption or antidiabetic effects. Preliminary data has shown potential benefits from bile acid co-encapsulation with PB. One bile acid has shown best potential improvement of PB oral delivery (ursodeoxycholic acid, UDCA). This study aimed to examine PB and UDCA microcapsules (with UDCA microcapsules serving as control) in terms of the microcapsules’ morphology, biological effects ex vivo, and their hypoglycemic and antilipidemic and anti-inflammatory effects in vivo. PBUDCA and UDCA microcapsules were examined in vitro (formulation studies), ex vivo and in vivo. PBUDCA microcapsules exerted positive effects on β-cells viability at hyperglycemic state, and brought about hypoglycemic and anti-inflammatory effects on the prediabetic mice. In conclusion, PBUDCA co-encapsulation have showed beneficial therapeutic impact of dual antioxidant-bile acid effects in diabetes treatment.

scholarly journals Tongxinluo Prevents Endothelial Dysfunction Induced by Homocysteine ThiolactoneIn Vivovia Suppression of Oxidative Stress

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Yi Zhang ◽  
Tiecheng Pan ◽  
Xiaoxuan Zhong ◽  
Cai Cheng
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Ex Vivo ◽  
Umbilical Vein ◽  
Protective Effects ◽  
Sod Activity ◽  
Homocysteine Thiolactone ◽  
Beneficial Effects ◽  
Umbilical Vein Endothelial Cells

Aim. To explore whether Chinese traditional medicine, tongxinluo (TXL), exerts beneficial effects on endothelial dysfunction induced by homocysteine thiolactone (HTL) and to investigate the potential mechanisms.Methods and Results. Incubation of cultured human umbilical vein endothelial cells with HTL (1 mM) for 24 hours significantly reduced cell viabilities assayed by MTT, and enhanced productions of reactive oxygen species. Pretreatment of cells with TXL (100, 200, and 400 μg/mL) for 1 hour reversed these effects induced by HTL. Further, coincubation with GW9662 (0.01, 0.1 mM) abolished the protective effects of TXL on HTL-treated cells. Inex vivoexperiments, exposure of isolated aortic rings from rats to HTL (1 mM) for 1 hour dramatically impaired acetylcholine-induced endothelium-dependent relaxation, reduced SOD activity, and increased malondialdehyde content in aortic tissues. Preincubation of aortic rings with TXL (100, 200, and 400 μg/mL) normalized the disorders induced by HTL. Importantly, all effects induced by TXL were reversed by GW9662.In vivoanalysis indicated that the administration of TXL (1.0 g/kg/d) remarkably suppressed oxidative stress and prevented endothelial dysfunction in rats fed with HTL (50 mg/kg/d) for 8 weeks.Conclusions. TXL improves endothelial functions in rats fed with HTL, which is related to PPARγ-dependent suppression of oxidative stress.

scholarly journals Protective Effects of Soy Oligopeptides in Ultraviolet B-Induced Acute Photodamage of Human Skin

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Bing-rong Zhou ◽  
Li-wen Ma ◽  
Juan Liu ◽  
Jia-an Zhang ◽  
Yang Xu ◽  
...  
Keyword(s):  
Protein Expression ◽  
Human Skin ◽  
Ex Vivo ◽  
P53 Protein ◽  
Ultraviolet B ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Apoptotic Cells ◽  
Protective Effects ◽  
Bax Protein

Aim. We explored the effects of soy oligopeptides (SOP) in ultraviolet B- (UVB-) induced acute photodamage of human skin in vivo and foreskin ex vivo. Methods. We irradiated the forearm with 1.5 minimal erythemal dose (MED) of UVB for 3 consecutive days, establishing acute photodamage of skin, and topically applied SOP. Erythema index (EI), melanin index, stratum corneum hydration, and transepidermal water loss were measured by using Multiprobe Adapter 9 device. We irradiated foreskin ex vivo with the same dose of UVB (180 mJ/cm2) for 3 consecutive days and topically applied SOP. Sunburn cells were detected by using hematoxylin and eosin staining. Apoptotic cells were detected by using terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Cyclobutane pyrimidine dimers (CPDs), p53 protein, Bax protein, and Bcl-2 protein were detected by using immunohistochemical staining. Results. Compared with UVB group, UVB-irradiated skin with topically applied SOP showed significantly decreased EI. Compared with UVB group, topical SOP significantly increased Bcl-2 protein expression and decreased CPDs-positive cells, sunburn cells, apoptotic cells, p53 protein expression, and Bax protein expressions in the epidermis of UVB-irradiated foreskin. Conclusion. Our study demonstrated that topical SOP can protect human skin against UVB-induced photodamage.

scholarly journals The safety profile of Bald’s eyesalve for the treatment of bacterial infections

2020 ◽  
Author(s):  
Blessing O Anonye ◽  
Valentine Nweke ◽  
Jessica Furner-Pardoe ◽  
Rebecca Gabrilska ◽  
Afshan Rafiq ◽  
...  
Keyword(s):  
Topical Application ◽  
Safety Profile ◽  
Bacterial Infections ◽  
Ex Vivo ◽  
Corneal Opacity ◽  
Healthy Human ◽  
Patch Tests ◽  
Human Volunteers

AbstractThe rise in antimicrobial resistance has prompted the development of alternatives, such as plant-derived compounds, to combat bacterial infections. Bald’s eyesalve, a remedy used in the Early Medieval period, has previously been shown to have efficacy against Staphylococcus aureus grown in an in vitro model of soft tissue infection. This remedy also had bactericidal activity against methicillin-resistant S. aureus (MRSA) in a chronic mouse wound. However, the safety profile of Bald’s eyesalve has not yet been demonstrated, and this is vital before testing in humans. Here, we determined the safety potential of Bald’s eyesalve using in vitro, ex vivo, and in vivo models representative of skin or eye infections. We also confirmed that Bald’s eyesalve is active against an important eye pathogen, Neisseria gonorrhoeae. Low levels of cytotoxicity were observed in eyesalve-treated cell lines representative of skin and immune cells. Results from a bovine corneal opacity and permeability test demonstrated slight irritation to the cornea that resolved within 10 minutes. The slug mucosal irritation assay revealed that a low level of mucus was secreted by slugs exposed to eyesalve, indicating mild mucosal irritation. We obtained promising results from mouse wound closure experiments; no visible signs of irritation or inflammation were observed. Our results suggest that Bald’s eyesalve could be tested further on human volunteers to assess safety for topical application against bacterial infections.ImportanceAlternative treatment for bacterial infections are needed to combat the ever increasing repertoire of bacteria resistant to antibiotics. A medieval plant-based remedy, Bald’s eyesalve, shows promise as a substitute for the treatment of these infections. For any substance to be effective in the treatment of bacterial infections in humans, it is important to consider the safety profile. This is a key consideration in order to have the necessary regulatory approval. We demonstrate the safety profile of Bald’s eyesalve using a variety of models, including whole-organ and whole-animal models. Our results show that Bald’s eyesalve is mildly toxic to cultured human cells, but potentially suitable for patch tests on healthy human volunteers to assess safety for later clinical trials. Our work has the potential to transform the management of diseases caused by bacterial infections, such as diabetic foot ulcers, through topical application of a natural product cocktail based on Bald’s eyesalve.

Abstract 18901: Calgranulins S100A8, S100A9 and S100A12 are Novel Genes Modified by n-3 PUFA Supplementation and Evoked Endotoxemia in Humans

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Jane F Ferguson ◽  
Chenyi Xue ◽  
Mingyao Li ◽  
Rachana Shah ◽  
Muredach P Reilly
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Low Grade ◽  
Protective Effects ◽  
Omega 3 ◽  
Healthy Individuals ◽  
Transcriptomic Response ◽  
Pufa Supplementation

Introduction: We have previously identified genes involved in the adipose transcriptomic response to evoked endotoxemia in humans. Long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA) may modulate chronic low-grade systemic and adipose inflammation, conferring protection in cardiometabolic disease. However, given subtle effects of n-3 PUFA in vivo, intervention studies often lack power to detect effects on resting biomarkers. We applied unbiased transcriptomics (RNASeq) to human adipose tissue in healthy individuals following supplementation with n-3 PUFA in combination with evoked endotoxemia (LPS) as a unique genomic discovery model in n-3 PUFA modulation of inflammation. Methods: Using RNASeq we analyzed transcriptomes of adipose tissue biopsies from healthy individuals at three timepoints: before and after n-3 PUFA supplementation (n=7; 3600mg/day EPA/DHA) for 6-8 weeks compared with placebo (n=6), as well as during a subsequent evoked inflammatory challenge (LPS 0.6 ng/kg I.V.). We further explored candidate gene expression in response to n-3 PUFA and LPS using human monocytes and adipocytes in vitro. Results: The transcriptomic response to LPS was altered by n-3 PUFA supplementation. We found increased up-regulation of calgranulin genes in n-3 PUFA (S100A8 16-fold, p=0.002; S100A9 8-fold, p=0.002; S100A12 32-fold, p=0.01) compared with placebo (S100A8 2-fold, p=0.003; S100A9 1.4-fold, p=0.4; S100A12 5-fold, p=0.04). These inflammasome-activating genes may be involved in atherogenesis and inflammatory diseases, and may play a role in the recruitment of inflammatory cells to adipose tissue. We found differing calgranulin gene expression in vitro in adipocytes and monocytes after n-3 PUFA (up in monocytes, down in adipocytes post DHA p<0.001) and LPS treatment (n-3 PUFA dependent decrease in monocytes, increase in adipocytes) consistent with n-3 PUFA-dependent cell-type-specific responses to inflammatory activation. Conclusions: Unbiased transcriptomics and evoked inflammation permits enhanced genomic discovery in the context of nutritional intervention. A novel mechanism of n-3 PUFA protective effects in vivo may be through modulation of expression of calgranulin genes in response to innate immune activation.

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