scholarly journals Ciprofloxacin reduces tenocyte viability and proteoglycan synthesis in short-term explant cultures of equine tendon

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12003
Author(s):  
Stuart James ◽  
Johannes Schuijers ◽  
John Daffy ◽  
Jill Cook ◽  
Tom Samiric
Keyword(s):  
Cell Viability ◽  
Bacterial Infections ◽  
Recovery Period ◽  
Proteoglycan Synthesis ◽  
Rna Expression ◽  
Increased Risk ◽  
Discontinuation Of Treatment ◽  
Superficial Digital Flexor Tendon ◽  
Underlying Mechanisms ◽  
Insight Into

Fluoroquinolones are an effective, broad-spectrum antibiotic used to treat an array of bacterial infections. However, they are associated with an increased risk of tendinopathy and tendon rupture even after discontinuation of treatment. This condition is known as fluoroquinolone-associated tendinopathy, the underlying mechanisms of which are poorly understood. While many factors may be involved in the pathophysiology of tendinopathies in general, changes in tenocyte metabolism and viability, as well as alteration of proteoglycan metabolism are prominent findings in the scientific literature. This study investigated the effects of ciprofloxacin, a common fluoroquinolone, on cell viability, proteoglycan synthesis, and proteoglycan mRNA expression in equine superficial digital flexor tendon explants after 96 h treatment with between 1–300 µg/mL ciprofloxacin, and again after 8 days discontinuation of treatment. Ciprofloxacin caused significant reductions in cell viability by between 25–33% at all dosages except 10 µg/mL, and viability decreased further after 8 days discontinuation of treatment. Proteoglycan synthesis significantly decreased by approximately 50% in explants treated with 100 µg/mL and 300 µg/mL, however this effect reversed after 8 days in the absence of treatment. No significant mRNA expression changes were observed after the treatment period with the exception of versican which was down-regulated at the highest concentration of ciprofloxacin. After the recovery period, aggrecan, biglycan and versican genes were all significantly downregulated in explants initially treated with 1–100 µg/mL. Results from this study corroborate previously reported findings of reduced cell viability and proteoglycan synthesis in a whole tissue explant model and provide further insight into the mechanisms underlying fluoroquinolone-associated tendinopathy and rupture. This study further demonstrates that certain ciprofloxacin induced cellular changes are not rapidly reversed upon cessation of treatment which is a novel finding in the literature.

scholarly journals Gram-Negative Bacterial Endotoxin LPS Induces NeuGc Loss through Ets1-Dependent Downregulation of Intestine-Specific pcmah Transcript in Porcine Intestinal Cells

2020 ◽  
Vol 21 (14) ◽  
pp. 4892
Author(s):  
Choong-Hwan Kwak ◽  
Kwon-Ho Song ◽  
Cheorl-Ho Kim
Keyword(s):  
Bacterial Infections ◽  
Defense Mechanism ◽  
Bacterial Endotoxin ◽  
Microbial Infection ◽  
Gram Negative ◽  
Acetylneuraminic Acid ◽  
Host Defense Mechanism ◽  
Small Intestinal ◽  
Underlying Mechanisms ◽  
Insight Into

N-glycolylneuraminic acid (NeuGc), a non-human sialic acid derivative synthesized by cytidine-5′-monophospho-N-acetylneuraminic acid hydroxylase (CMAH), plays a crucial role in mediating infections by certain pathogens. Although it has been postulated that NeuGc biosynthesis and CMAH expression are downregulated during microbial infection, the underlying mechanisms remain unclear. The present study showed that exposure to lipopolysaccharide (LPS), a Gram-negative bacterial endotoxin, leads to loss of NeuGc biosynthesis in pig small intestinal I2I-2I cells. This LPS-induced NeuGc loss was accompanied by decreased CMAH transcript levels, especially intestine-specific 5′pcmah-1. Furthermore, LPS suppressed the activity of the Pi promoter responsible for 5′pcmah-1 by inhibiting DNA binding of Est1. These findings provide insight into the regulatory mechanisms of Neu5Gc biosynthesis during pathogenic infectious events, which may represent a host defense mechanism that protects the self against pathogenic bacterial infections even in non-sanitary environments.

The Effect of Exercise and Distraction on Blood Pressure Recovery Following an Anger-Provoking Stressor in Normotensive Young Adults

2015 ◽  
Vol 29 (2) ◽  
pp. 45-54 ◽  
Author(s):  
Faye S. Routledge ◽  
Judith A. McFetridge-Durdle ◽  
Marilyn Macdonald ◽  
Lynn Breau ◽  
Tavis Campbell
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Health ◽  
Exercise Intervention ◽  
Recovery Period ◽  
Intervention Group ◽  
Exercise Group ◽  
State Anger ◽  
Increased Risk ◽  
Anger Reactivity ◽  
Quiet Sitting

Ruminating about a prior anger provoking event is found to elevate blood pressure (BP) and delay BP recovery. Delayed BP recovery may be associated with increased risk of hypertension. Interventions that improve BP recovery may be beneficial for cardiovascular health. The purposes of this study were to evaluate the influence of rumination and anger on BP reactivity and recovery, to compare the effect of an exercise intervention or distraction intervention on BP recovery and to explore if exercise improved BP recovery by distracting participants from stressor-related rumination and anger. Healthy, normotensive participants (n = 79, mean age 22.2 ± 4.0 years) underwent an anger-recall interview stressor task, 3 min of exercise (walking), distraction (reading) or no-intervention (quiet sitting) and a 15 min recovery period. State anger reactivity was associated with Δ diastolic (D) BP reactivity and approached significance with Δ systolic (S) BP reactivity. Trait rumination was associated with greater SBP during recovery. Δ SBP recovery did not differ between the exercise, distraction and no-intervention groups. Although there were no differences in Δ DBP recovery between the exercise and no-intervention groups, distraction improved Δ DBP recovery compared to the exercise intervention but not the no-intervention. The proportion of anger-related thoughts (state rumination) in the exercise group did not differ from the distraction or no-intervention groups. However, a smaller proportion of participants in the distraction intervention reported an anger-related thought during recovery compared to the no-intervention group with 76% of their thoughts relating to the provided distraction. Overall, post-stressor exercise was not found to improve BP recovery while reading was effective at distracting individuals from angry thoughts (state rumination) but had no effect on BP compared to no-intervention.

Mechanisms underlying heart failure in type 2 diabetes mellitus

2019 ◽  
pp. 37-39
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Experimental Studies ◽  
Vascular Complications ◽  
Molecular Alterations ◽  
Increased Risk ◽  
Cardioprotective Effects ◽  
Underlying Mechanisms ◽  
Cardio Vascular

The prevalence of heart failure is markedly increased in individuals with diabetes mellitus. Numerous observational studies suggest that this increased risk for heart failure can be attributed to exacerbated vascular complications and the presence of increased risk factors in diabetic subjects. In addition, experimental studies revealed the presence of a number of distinct molecular alterations in the myocardium that occur independently of vascular disease and hypertension. Many of these molecular alterations are similarly observed in failing hearts of nondiabetic patients and have thus been proposed to contribute to the increased risk for heart failure in diabetes. The interest in understanding the underlying mechanisms of impaired cardio- vascular outcomes in diabetic individuals has much increased since the demonstration of cardioprotective effects of SGLT-2 inhibitors and GLP-1 receptor agonists in recent clinical trials. The current review therefore summarizes the distinct mechanisms that have been proposed to increase the risk for heart failure in diabetes mellitus.

The Effects of Butyric Acid on the Differentiation, Proliferation, Apoptosis, and Autophagy of IPEC-J2 Cells

2020 ◽  
Vol 20 (4) ◽  
pp. 307-317
Author(s):  
Yuan Yang ◽  
Jin Huang ◽  
Jianzhong Li ◽  
Huansheng Yang ◽  
Yulong Yin
Keyword(s):  
Cell Viability ◽  
P38 Mapk ◽  
Butyric Acid ◽  
Cell Apoptosis ◽  
Mapk Pathway ◽  
Mrna Level ◽  
Dependent Manner ◽  
M Phase ◽  
High Concentrations ◽  
Underlying Mechanisms

Background: Butyric acid (BT), a short-chain fatty acid, is the preferred colonocyte energy source. The effects of BT on the differentiation, proliferation, and apoptosis of small intestinal epithelial cells of piglets and its underlying mechanisms have not been fully elucidated. Methods: In this study, it was found that 0.2-0.4 mM BT promoted the differentiation of procine jejunal epithelial (IPEC-J2) cells. BT at 0.5 mM or higher concentrations significantly impaired cell viability in a dose- and time-dependent manner. In addition, BT at high concentrations inhibited the IPEC-J2 cell proliferation and induced cell cycle arrest in the G2/M phase. Results: Our results demonstrated that BT triggered IPEC-J2 cell apoptosis via the caspase8-caspase3 pathway accompanied by excess reactive oxygen species (ROS) and TNF-α production. BT at high concentrations inhibited cell autophagy associated with increased lysosome formation. It was found that BT-reduced IPEC-J2 cell viability could be attenuated by p38 MAPK inhibitor SB202190. Moreover, SB202190 attenuated BT-increased p38 MAPK target DDIT3 mRNA level and V-ATPase mRNA level that were responsible for normal acidic lysosomes. Conclusion: In conclusion, 1) at 0.2-0.4 mM, BT promotes the differentiation of IPEC-J2 cells; 2) BT at 0.5 mM or higher concentrations induces cell apoptosis via the p38 MAPK pathway; 3) BT inhibits cells autophagy and promotes lysosome formation at high concentrations.

Could Antioxidant Supplementation Delay Progression of Cardiovascular Disease in End-Stage Renal Disease Patients?

2020 ◽  
Vol 19 (1) ◽  
pp. 41-54 ◽  
Author(s):  
Stefanos Roumeliotis ◽  
Athanasios Roumeliotis ◽  
Xenia Gorny ◽  
Peter R. Mertens
Keyword(s):  
Oxidative Stress ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Close Association ◽  
Omega 3 ◽  
Endstage Renal Disease ◽  
Increased Risk ◽  
Underlying Mechanisms ◽  
Stage Renal Disease ◽  
End Stage

In end-stage renal disease patients, the leading causes of mortality are of cardiovascular (CV) origin. The underlying mechanisms are complex, given that sudden heart failure is more common than acute myocardial infarction. A contributing role of oxidative stress is postulated, which is increased even at early stages of chronic kidney disease, is gradually augmented in parallel to progression to endstage renal disease and is further accelerated by renal replacement therapy. Oxidative stress ensues when there is an imbalance between reactive pro-oxidants and physiologically occurring electron donating antioxidant defence systems. During the last decade, a close association of oxidative stress with accelerated atherosclerosis and increased risk for CV and all-cause mortality has been established. Lipid peroxidation has been identified as a trigger for endothelial dysfunction, the first step towards atherogenesis. In order to counteract the deleterious effects of free radicals and thereby ameliorate, or delay, CV disease, exogenous administration of antioxidants has been proposed. Here, we attempt to summarize existing data from studies that test antioxidants for CV protection, such as vitamins E and C, statins, omega-3 fatty acids and N-acetylcysteine.

A Review of Phytochemical and Pharmacological Studies of Inula Species

2020 ◽  
Vol 16 (5) ◽  
pp. 557-567
Author(s):  
Aparoop Das ◽  
Anshul Shakya ◽  
Surajit Kumar Ghosh ◽  
Udaya P. Singh ◽  
Hans R. Bhat
Keyword(s):  
Bacterial Infections ◽  
Chemical Constituents ◽  
Valuable Insight ◽  
Important Ingredient ◽  
Pharmacological Activities ◽  
Medicinal Uses ◽  
The Family ◽  
Pharmacological Studies ◽  
Perennial Herbs ◽  
Insight Into

Background: Plants of the genus Inula are perennial herbs of the family Asteraceae. This genus includes more than 100 species, widely distributed throughout Europe, Africa and Asia including India. Many of them are indicated in traditional medicine, e.g., in Ayurveda. This review explores chemical constituents, medicinal uses and pharmacological actions of Inula species. Methods: Major databases and research and review articles retrieved through Scopus, Web of Science, and Medline were consulted to obtain information on the pharmacological activities of the genus Inula published from 1994 to 2017. Results: Inula species are used either alone or as an important ingredient of various formulations to cure dysfunctions of the cardiovascular system, respiratory system, urinary system, central nervous system and digestive system, and for the treatment of asthma, diabetes, cancers, skin disorders, hepatic disease, fungal and bacterial infections. A range of phytochemicals including alkaloids, essential and volatile oils, flavonoids, terpenes, and lactones has been isolated from herbs of the genus Inula, which might possibly explain traditional uses of these plants. Conclusion: The present review is focused on chemical constituents, medicinal uses and pharmacological actions of Inula species and provides valuable insight into its medicinal potential.

scholarly journals Continuous and Cyclic Progesterone Differentially Interact with Estradiol in the Regulation of Alzheimer-Like Pathology in Female 3×Transgenic-Alzheimer’s Disease Mice

Endocrinology ◽  
2010 ◽  
Vol 151 (6) ◽  
pp. 2713-2722 ◽  
Author(s):  
Jenna C. Carroll ◽  
Emily R. Rosario ◽  
Angela Villamagna ◽  
Christian J. Pike
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Postmenopausal Women ◽  
Transgenic Mouse Model ◽  
Dependent Behavior ◽  
Potential Efficacy ◽  
Increased Risk ◽  
Neural Interactions ◽  
Β Amyloid ◽  
Insight Into

Depletion of estrogens and progesterone at menopause has been linked to an increased risk for the development of Alzheimer’s disease (AD) in women. A currently controversial literature indicates that although treatment of postmenopausal women with hormone therapy (HT) may reduce the risk of AD, several parameters of HT may limit its potential efficacy and perhaps, even exacerbate AD risk. One such parameter is continuous vs. cyclic delivery of the progestogen component of HT. Recent experimental evidence suggests that continuous progesterone can attenuate neural actions of estradiol (E2). In the present study, we compared the effects of continuous and cyclic progesterone treatment in the presence and absence of E2 in ovariectomized 3×Tg-AD mice, a transgenic mouse model of AD. We found that ovariectomy-induced hormone depletion increases AD-like pathology in female 3×Tg-AD mice, including accumulation of β-amyloid, tau hyperphosphorylation, and impaired hippocampal-dependent behavior. E2 treatment alone prevents the increases in pathology. Continuous progesterone did not affect β-amyloid levels when delivered alone but blocked the Aβ-lowering action of E2. In contrast, cyclic progesterone significantly reduced β-amyloid levels by itself and enhanced rather than inhibited the E2 effects. These results provide new insight into the neural interactions between E2 and progesterone that may prove valuable in optimizing HT regimens in postmenopausal women.

scholarly journals Good Idea But Not Here! A Pilot Study of Swedish Tourism Stakeholders’ Perceptions of Halal Tourism

2021 ◽  
Vol 13 (5) ◽  
pp. 2646
Author(s):  
Saeid Abbasian
Keyword(s):  
Content Analysis ◽  
Pilot Study ◽  
Tourism Industry ◽  
Target Group ◽  
Exploratory Research ◽  
Swedish Study ◽  
Increased Risk ◽  
Insight Into

The following study is the first Swedish study on Halal tourism in Sweden. The purpose of this exploratory research is to get insight into the perception of Halal tourism in Sweden among representatives of tourism stakeholders. The overall methodology approach in this research is qualitative, consisting of 25 qualitative questionnaires, 21 short letters, four follow-up interviews, and a web observation, and content analysis was employed. The results indicate that there is a low knowledge of Halal tourism in Sweden including Swedish tourism industry. The concept is very challenging, and profits are low. It might result in problem scenarios such as detrimental effects on non-Halal tourism, cultural difficulties and increased risk of xenophobia, anti-Islamism, and tension in the society. There is low interest for Sweden among Muslim tourists as the interest and priority for Halal tourism is rather low from Swedish tourism industry. Despite Halal tourism’s importance internationally, these representatives are rather cautious and doubtful about promotion of Sweden towards this niche. Still, a majority seems to be positive to a lighter version of Muslim-friendly tourism with secular/moderate Muslims as a target group.

scholarly journals Gut Microbiome and Metabolome Profiles Associated with High-Fat Diet in Mice

Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 482
Author(s):  
Jae-Kwon Jo ◽  
Seung-Ho Seo ◽  
Seong-Eun Park ◽  
Hyun-Woo Kim ◽  
Eun-Ju Kim ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Relative Abundance ◽  
High Fat Diet ◽  
Amplicon Sequencing ◽  
Gas Chromatography Mass Spectrometry ◽  
Control Group ◽  
Rrna Gene ◽  
High Fat ◽  
Underlying Mechanisms ◽  
Insight Into

Obesity can be caused by microbes producing metabolites; it is thus important to determine the correlation between gut microbes and metabolites. This study aimed to identify gut microbiota-metabolomic signatures that change with a high-fat diet and understand the underlying mechanisms. To investigate the profiles of the gut microbiota and metabolites that changed after a 60% fat diet for 8 weeks, 16S rRNA gene amplicon sequencing and gas chromatography-mass spectrometry (GC-MS)-based metabolomic analyses were performed. Mice belonging to the HFD group showed a significant decrease in the relative abundance of Bacteroidetes but an increase in the relative abundance of Firmicutes compared to the control group. The relative abundance of Firmicutes, such as Lactococcus, Blautia, Lachnoclostridium, Oscillibacter, Ruminiclostridium, Harryflintia, Lactobacillus, Oscillospira, and Erysipelatoclostridium, was significantly higher in the HFD group than in the control group. The increased relative abundance of Firmicutes in the HFD group was positively correlated with fecal ribose, hypoxanthine, fructose, glycolic acid, ornithine, serum inositol, tyrosine, and glycine. Metabolic pathways affected by a high fat diet on serum were involved in aminoacyl-tRNA biosynthesis, glycine, serine and threonine metabolism, cysteine and methionine metabolism, glyoxylate and dicarboxylate metabolism, and phenylalanine, tyrosine, and trypto-phan biosynthesis. This study provides insight into the dysbiosis of gut microbiota and metabolites altered by HFD and may help to understand the mechanisms underlying obesity mediated by gut microbiota.

scholarly journals Superhydrophobic Nanocoatings as Intervention against Biofilm-Associated Bacterial Infections

Nanomaterials ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 1046
Author(s):  
Yinghan Chan ◽  
Xun Hui Wu ◽  
Buong Woei Chieng ◽  
Nor Azowa Ibrahim ◽  
Yoon Yee Then
Keyword(s):  
Biofilm Formation ◽  
Bacterial Infections ◽  
Therapeutic Strategies ◽  
Public Healthcare ◽  
Persistent Infections ◽  
Promising Strategy ◽  
Antimicrobial Interventions ◽  
Novel Therapeutic Strategies ◽  
Insight Into ◽  
Microbial Attachment

Biofilm formation represents a significant cause of concern as it has been associated with increased morbidity and mortality, thereby imposing a huge burden on public healthcare system throughout the world. As biofilms are usually resistant to various conventional antimicrobial interventions, they may result in severe and persistent infections, which necessitates the development of novel therapeutic strategies to combat biofilm-based infections. Physicochemical modification of the biomaterials utilized in medical devices to mitigate initial microbial attachment has been proposed as a promising strategy in combating polymicrobial infections, as the adhesion of microorganisms is typically the first step for the formation of biofilms. For instance, superhydrophobic surfaces have been shown to possess substantial anti-biofilm properties attributed to the presence of nanostructures. In this article, we provide an insight into the mechanisms underlying biofilm formation and their composition, as well as the applications of nanomaterials as superhydrophobic nanocoatings for the development of novel anti-biofilm therapies.

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