Staphylococcus pasteuri isolates (Spvs) from human atherosclerotic plaques mediate virulence, intracellular resistance and transendothelial invasion of macrophages: A mechanistic paradigm for microbial pathogenicity in atherosclerosis

2019 ◽  
Author(s):  
Nasreen S. Haque ◽  
Jayesh Modi ◽  
Niloufar Haque ◽  
Igor Laskpwski ◽  
Romeo B. Mateo ◽  
...  
Keyword(s):  
Decisive Role ◽  
Infectious Agent ◽  
Endothelial Cell Migration ◽  
Human Consumption ◽  
Atherosclerotic Cardiovascular Disease ◽  
Plaque Vulnerability ◽  
Contributing Factors ◽  
Intracellular Resistance ◽  
Chronic Inflammatory Condition ◽  
Pure Cultures

AbstractAtherosclerotic cardiovascular disease, a chronic inflammatory condition of multifactorial etiology, is the leading cause of death worldwide. The concept of ‘bacterial persistence’ has been proposed as one of several contributing factors to this disease. We hypothesized that the infectious agent(s) found at the site of the atheroma may be dormant but perpetuate virulence in response to host defense and other physiological triggers. In this study, we sought to identify the source of persistent infection in human atherosclerotic plaque and define how pathogen virulence and host defenses mediate plaque vulnerability. Whole genome sequencing (WGS) was used to identify bacteria from pure cultures obtained from atherosclerotic tissues of living subjects diagnosed with more than 70% occlusion of the carotid artery undergoing carotid endarterectomy (CE). WGS identified the predominant species as S. pasteuri (Spv) in all CE isolates grown in pure culture except one isolate which was identified as B. licheniformis. All S. pasteuri isolates (Spvs) were found to contain genes for widespread virulence, invasion, and intracellular resistance. As macrophages (Mφs) play a decisive role at all stages of this disease we treated mouse Mφs (RAW 264.7) with Spvs. While all Spvs tested demonstrated their ability to survive phagocytosis, the highly virulent Spvs also activated Mφs and induced trans-endothelial cell migration of these cells which was mediated via the CC chemokine CCL1 and its receptor CCR8. In conclusion, we show that Spvs are found in CE plaques, have the capacity to survive phagocytosis and induce the transmigration of Mφs across an endothelial barrier in a CCL1-CCR8 dependent process. These findings highlight the significance of carotid vessels as a reservoir for S. pasteuri, a pathogen found in products used routinely in human consumption; this may explain how microbial pathogenicity modulates plaque vulnerability in atherosclerosis.

scholarly journals IL-17 Pathway Members as Potential Biomarkers of Effective Systemic Treatment and Cardiovascular Disease in Patients with Moderate-to-Severe Psoriasis

2022 ◽  
Vol 23 (1) ◽  
pp. 555
Author(s):  
Xing Wang ◽  
Hannah Kaiser ◽  
Amanda Kvist-Hansen ◽  
Benjamin D. McCauley ◽  
Lone Skov ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Plasma Proteins ◽  
Systemic Treatment ◽  
Severe Psoriasis ◽  
Atherosclerotic Cardiovascular Disease ◽  
Strong Correlations ◽  
Potential Marker ◽  
Chronic Inflammatory Condition ◽  
Circulating Levels ◽  
Potential Biomarkers

Psoriasis is a chronic inflammatory condition associated with atherosclerotic cardiovascular disease (CVD). Systemic anti-psoriatic treatments mainly include methotrexate and biological therapies targeting TNF, IL-12/23 and IL-17A. We profiled plasma proteins from patients with moderate-to-severe psoriasis to explore potential biomarkers of effective systemic treatment and their relationship to CVD. We found that systemically well-treated patients (PASI < 3.0, n = 36) had lower circulating levels of IL-17 pathway proteins compared to untreated patients (PASI > 10, n = 23). Notably, IL-17C and PI3 were decreased with all four examined systemic treatment types. Furthermore, in patients without CVD, we observed strong correlations among IL-17C/PI3/PASI (r ≥ 0.82, p ≤ 1.5 × 10−12) pairs or between IL-17A/PASI (r = 0.72, p = 9.3 × 10−8). In patients with CVD, the IL-17A/PASI correlation was abolished (r = 0.2, p = 0.24) and the other correlations were decreased, e.g., IL-17C/PI3 (r = 0.61, p = 4.5 × 10−5). Patients with moderate-to-severe psoriasis and CVD had lower levels of IL-17A compared to those without CVD (normalized protein expression [NPX] 2.02 vs. 2.55, p = 0.013), and lower IL-17A levels (NPX < 2.3) were associated with higher incidence of CVD (OR = 24.5, p = 0.0028, 95% CI 2.1–1425.1). As a result, in patients with moderate-to-severe psoriasis, we propose circulating IL-17C and PI3 as potential biomarkers of effective systemic anti-psoriatic treatment, and IL-17A as potential marker of CVD.

scholarly journals H2O2 downregulate SIRT7`s protective role of endothelial premature dysfunction via microRNA-335-5p

2022 ◽  
Author(s):  
Yixin Liu ◽  
Jinyu Yang ◽  
Xi Yang ◽  
Peng Lai ◽  
Yi Mou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Risk Factors ◽  
Endothelial Cells ◽  
Umbilical Vein ◽  
Protective Role ◽  
Atherosclerotic Cardiovascular Disease ◽  
Contributing Factors ◽  
Age Related ◽  
Underlying Mechanisms ◽  
Umbilical Vein Endothelial Cells

Endothelial senescence is believed to constitute the initial pathogenesis of the atherosclerotic cardiovascular disease (ASCVD). MicroRNA-335-5p (miR-335-5p) expression is significantly upregulated in oxidative stress-induced endothelial cells (ECs). Sirtuin7 (SIRT7) is considered to prevent EC senescence, yet data on its response to ASCVD risk factors are limited. This study analyzed the elevated levels of miR-335-5p and the decreased levels of SIRT7 in human umbilical vein endothelial cells (HUVECs) , and found that high glucose, tumour necrosis factor-α (TNF-α), and H2O2 are the three contributing factors that induced cellular senescence. The current study also assessed premature endothelial senescence and decreased proliferation, adhesion, migration, and nitric oxide secretion in HUVECs with these risk factors together with SIRT7-siRNA transfection. It found that the miR-335-5p inhibitor attenuated the downregulation of SIRT7 expression induced by oxidative stress in HUVECs, and SIRT7 overexpression exerts a rescue effect against miR-335-5p induced endothelial dysfunction. Furthermore, the direct binding of miR-335-5p to SIRT7 was observed in HEK-293T. Therefore, it can be inferred that miR-335-5p downregulates the expression of SIRT7 in human cells. Current findings may provide deeper insights into the underlying mechanisms of endothelial senescence and potential therapeutic targets of ASCVD as well as other age-related diseases.

scholarly journals Concentrations of Some Trace Elements in Vegetables Sold at Maun Market, Botswana

2016 ◽  
Vol 6 (1) ◽  
pp. 69 ◽  
Author(s):  
Keagile Bati ◽  
Oarabile Mogobe ◽  
Wellington R. L. Masamba
Keyword(s):  
Toxic Metals ◽  
Inductively Coupled Plasma ◽  
Toxic Elements ◽  
Atomic Emission ◽  
Essential Elements ◽  
Leafy Vegetables ◽  
Human Consumption ◽  
Open Market ◽  
Contributing Factors ◽  
Street Vendor

Contamination of vegetables with toxic metals is one of the most important contributing factors to ill health throughout the world, more so because vegetables are considered essential for human health and their consumption is highly recommended by health authorities. The aim of this study was to determine the concentrations of selected essential elements (Fe, Cu, Mn, Mo, Zn) and toxic elements (As, Cd, Cr, Pb) in common vegetables sold for human consumption in supermarkets and open market of Maun village, Botswana. Five vegetables (cabbage, rape, tomatoes, onions and potatoes) were purchased from different selling points, washed with de-ionised water, cut into small pieces and digested with aqua regia on a block digester, following the US. EPA method 200 - 7 and analysed for metal content using Inductively Coupled Plasma - Atomic Emission Spectroscopy (ICP-AES). The results showed that concentrations of essential and toxic metals varied with the type of vegetable and also with the market category (supermarket or street vendor). The highest concentration of essential elements was obtained from cabbage with a Zn concentration of 135.4mg/Kg and the lowest was from onion with a Mo concentration of 1.35mg/Kg. For toxic elements the highest concentration was obtained from rape vegetable with a Pb concentration of 4.73mg/Kg and the lowest from the same vegetable with Cr concentration below the detection limit. Also observed was that leafy vegetables, especially cabbage, had the highest concentrations of most trace metals. It was concluded that vegetables sold in Maun had sufficient levels of essential elements but also some had high concentrations of toxic metals. We thus recommend consumption of vegetables from the studied markets with reduced frequency to avoid metal poisoning.

Vaginal Cancer: An Iatrogenic Disease?

1975 ◽  
Vol 5 (2) ◽  
pp. 235-251 ◽  
Author(s):  
Kay Weiss
Keyword(s):  
Public Health ◽  
In Utero ◽  
Vaginal Cancer ◽  
Current Status ◽  
Human Consumption ◽  
Contributing Factors ◽  
Drug Induced ◽  
Cattle Feed ◽  
University Women ◽  
Epidemiologic Evidence

Presently we are witnessing two unique occurrences in the field of public health: the first demonstration of transplacental carcinogenesis in humans and the first drug-induced cancer epidemic in women under age 30. This article examines the current status of the vaginal cancer epidemic and possible reasons for the failure of governmental health agencies to recall and test the generation of females who were exposed to diethylstilbestrol (DES) in utero. Epidemiologic evidence indicates that the large majority of “DES daughters” may develop adenosis. The carcinogenicity of other estrogens in wide use is examined. It is pointed out that, although vaginal cancer in daughters exposed to DES in utero provided the clinical evidence to secure a Food and Drug Administration ban on DES as an additive to cattle feed, the FDA approved a new use of DES as a “morning-after pill” contraceptive even though the contraceptive contains 833,000 times the amount of DES banned for human consumption in beef. The lack of standards of informed consent in the testing of the morning-after pill on university women and the additional risk this presents to DES daughters are discussed. The sociopolitical and economic contributing factors to the vaginal cancer epidemic and the extent to which the scientific direction of medical care is influenced by economic factors are examined. Public health measures which might prevent the occurrence of such man-made epidemics in the future are recommended.

scholarly journals Mycobacterium Avium Paratuberculosisand the Etiology of Crohn’s Disease: A Review of the Controversy from the Clinician’s Perspective

2010 ◽  
Vol 24 (10) ◽  
pp. 619-624 ◽  
Author(s):  
Greg Rosenfeld ◽  
Brian Bressler
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mycobacterium Avium ◽  
Immunosuppressive Agents ◽  
Infectious Agent ◽  
Causative Role ◽  
Mycobacterium Avium Paratuberculosis ◽  
Considerable Research ◽  
Chronic Inflammatory Condition

Mycobacterium avium paratuberculosis(MAP) is an obligate intracellular organism that has frequently been associated with Crohn’s disease (CD). Because CD is a chronic inflammatory condition, many researchers have speculated that an infectious agent must be the cause of CD. MAP has often been proposed to be one such agent; however, despite considerable research, the evidence remains inconclusive. Higher levels of MAP have been found in the tissues and blood of CD patients than in controls, forming the foundation for much of the research into the role of MAP in CD and the primary argument in support of a causative role for MAP in CD. MAP is a slow-growing and fastidious organism that is difficult to grow in culture and, therefore, challenging to detect in patients. As a result, there has been variability in the results of studies attempting to detect the presence of MAP in CD patients, and considerable controversy over whether this organism has a causative role in the etiology of CD. Two main hypotheses exist with respect to the role of MAP in CD. The first is that MAP is a principal cause of CD, while the second is that MAP is more prevalent because of the immune dysfunction seen in CD but does not play a causative role. Clinicians are often faced with questions regarding the role of this organism and the need to treat it. The present article attempts to provide an overview of the controversy including the nature of the mycobacterium, the difficulty in detecting it, the use of antimycobacterial agents to treat it and the effect of immunosuppressive agents – all from a clinician’s perspective. Although the role of MAP in CD remains controversial and an area of considerable research, it is currently only of academic interest because there is no clinically useful test to identify the presence of the organism, and no evidence to support the use of antibiotics to eradicate it for the treatment of CD.

Running Exercise and Angiotensin II Type I Receptor Blocker Telmisartan Are Equally Effective in Preventing Angiotensin II-Mediated Vulnerable Atherosclerotic Lesions

2016 ◽  
Vol 22 (2) ◽  
pp. 159-168 ◽  
Author(s):  
Maxime Pellegrin ◽  
Justyna Szostak ◽  
Karima Bouzourène ◽  
Jean-François Aubert ◽  
Alain Berthelot ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Receptor Expression ◽  
Treadmill Running ◽  
Receptor Blocker ◽  
Atherosclerotic Cardiovascular Disease ◽  
Type I ◽  
Ang Ii ◽  
T Helper ◽  
Plaque Vulnerability ◽  
Running Exercise

Introduction: The present study was conducted to directly compare the efficacy of running exercise and telmisartan treatment on angiotensin (Ang) II-mediated atherosclerosis and plaque vulnerability. Materials and Methods: Apolipoprotein E-deficient (ApoE−/−) mice with Ang II-mediated atherosclerosis (2-kidney, 1-clip [2K1C] renovascular hypertension model) were randomized into 3 groups: treadmill running exercise (RUN), telmisartan treatment (TEL), and sedentary untreated controls (SED) for 5 weeks. Atherosclerosis was assessed using histological and immunohistochemical analyses. Gene expression was determined by real-time reverse transcription polymerase chain reaction. Results: TEL but not RUN mice significantly decreased (50%) atherosclerotic lesion size compared to SED. RUN and TEL promoted plaque stabilization to a similar degree in ApoE−/− 2K1C mice. However, plaque composition and vascular inflammatory markers were differently affected: RUN decreased plaque macrophage infiltration (35%), whereas TEL reduced lipid core size (88%); RUN significantly increased aortic peroxisome proliferator-activated receptor (PPAR)-α, -δ, and -γ expression, whereas TEL significantly modulated T-helper 1/T-helper 2 (Th1/Th2) aortic response toward an anti-inflammatory state (decreased aortic interleukin [IL] 2 to IL-10 and IL-2 to IL-13 expression ratios). Plaque smooth muscle cell content was similarly increased (128% and 141%, respectively). Aortic AT1 and AT2 receptor expression as well as aortic CD11c/CD206 and IL-1β/IL-1ra expression ratios were not significantly modulated by either RUN or TEL. Conclusion: Running exercise and telmisartan treatment are equally effective in preventing Ang II-mediated plaque vulnerability but through distinct cellular and molecular mechanisms. Our findings further support the use of exercise training and selective AT1 receptor blocker therapies for atherosclerotic cardiovascular disease prevention.

scholarly journals Production Significance of Bovine Respiratory Disease Lesions in Slaughtered Beef Cattle

Animals ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1770
Author(s):  
Miguel Fernández ◽  
María del Carmen Ferreras ◽  
Francisco Javier Giráldez ◽  
Julio Benavides ◽  
Valentín Pérez
Keyword(s):  
Beef Cattle ◽  
Respiratory Disease ◽  
Management System ◽  
Bacterial Infections ◽  
Bovine Respiratory Disease ◽  
Infectious Agent ◽  
Carcass Weight ◽  
Human Consumption ◽  
Associated Lesions ◽  
Production Values

Bovine respiratory disease (BRD) is still a serious concern in feedlots, where it exerts a negative effect on farm productivity. There is a shortage of studies focused on the evaluation of BRD-associated lesions at the slaughterhouse in clinically healthy animals. The objective of this work was to investigate the prevalence and type of subclinical pneumonic lesions in slaughtered beef cattle, according to the age range and management system, and its impact on carcass weight. A total of 1101 beef cattle intended for human consumption were examined at slaughter. Information on age, sex, management system and carcass weight was recorded. The presence and type of pneumonia were evaluated according to gross and microscopic findings and etiological agents by PCR. Lung pneumonic lesions appeared in 17.9% of animals and were predominant among veal calves. According to the type, chronic catarrhal pneumonia prevailed in the majority of animals, and mixed and extensively reared cattle were more likely to suffer acute fibrinous pneumonia. The presence of pneumonic lesions was associated with a significant decrease in carcass weight that had more of an impact in veal male calves coming from intensive systems. Bacterial infections were the predominant infectious agent and the only cause of acute fibrinous pneumonia, while viruses were infrequent and only found in lesions with chronic catarrhal pneumonia. This study shows the importance of BRD in beef feedlots upon production values and points out the feasibility of slaughterhouse assessment of pneumonia as a method for the evaluation of BRD significance.

Use of TEM in Plant Disease Diagnosis: A Xylem-Limited Bacterium Associated with Diseased ‘Toronto’ Creeping Bentgrass

1981 ◽  
Vol 39 ◽  
pp. 414-415
Author(s):  
Karen K. Baker ◽  
David L. Roberts
Keyword(s):  
Osmium Tetroxide ◽  
Plant Disease ◽  
Leaf Tissue ◽  
Infectious Agent ◽  
Creeping Bentgrass ◽  
Disease Diagnosis ◽  
Unknown Etiology ◽  
Agrostis Palustris ◽  
Putting Greens ◽  
Plant Disease Diagnosis

Plant disease diagnosis is most often accomplished by examination of symptoms and observation or isolation of causal organisms. Occasionally, diseases of unknown etiology occur and are difficult or impossible to accurately diagnose by the usual means. In 1980, such a disease was observed on Agrostis palustris Huds. c.v. Toronto (creeping bentgrass) putting greens at the Butler National Golf Course in Oak Brook, IL.The wilting symptoms of the disease and the irregular nature of its spread through affected areas suggested that an infectious agent was involved. However, normal isolation procedures did not yield any organism known to infect turf grass. TEM was employed in order to aid in the possible diagnosis of the disease.Crown, root and leaf tissue of both infected and symptomless plants were fixed in cold 5% glutaraldehyde in 0.1 M phosphate buffer, post-fixed in buffered 1% osmium tetroxide, dehydrated in ethanol and embedded in a 1:1 mixture of Spurrs and epon-araldite epoxy resins.

Elevated level of circulatory sTLT1 induces inflammation through SYK/MEK/ERK signalling in coronary artery disease

2019 ◽  
Vol 133 (22) ◽  
pp. 2283-2299
Author(s):  
Apabrita Ayan Das ◽  
Devasmita Chakravarty ◽  
Debmalya Bhunia ◽  
Surajit Ghosh ◽  
Prakash C. Mandal ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Chronic Inflammation ◽  
Ex Vivo ◽  
Human Subjects ◽  
Critical Role ◽  
Atherosclerotic Cardiovascular Disease ◽  
Tnf Α ◽  
Artery Disease

Abstract The role of inflammation in all phases of atherosclerotic process is well established and soluble TREM-like transcript 1 (sTLT1) is reported to be associated with chronic inflammation. Yet, no information is available about the involvement of sTLT1 in atherosclerotic cardiovascular disease. Present study was undertaken to determine the pathophysiological significance of sTLT1 in atherosclerosis by employing an observational study on human subjects (n=117) followed by experiments in human macrophages and atherosclerotic apolipoprotein E (apoE)−/− mice. Plasma level of sTLT1 was found to be significantly (P<0.05) higher in clinical (2342 ± 184 pg/ml) and subclinical cases (1773 ± 118 pg/ml) than healthy controls (461 ± 57 pg/ml). Moreover, statistical analyses further indicated that sTLT1 was not only associated with common risk factors for Coronary Artery Disease (CAD) in both clinical and subclinical groups but also strongly correlated with disease severity. Ex vivo studies on macrophages showed that sTLT1 interacts with Fcɣ receptor I (FcɣRI) to activate spleen tyrosine kinase (SYK)-mediated downstream MAP kinase signalling cascade to activate nuclear factor-κ B (NF-kB). Activation of NF-kB induces secretion of tumour necrosis factor-α (TNF-α) from macrophage cells that plays pivotal role in governing the persistence of chronic inflammation. Atherosclerotic apoE−/− mice also showed high levels of sTLT1 and TNF-α in nearly occluded aortic stage indicating the contribution of sTLT1 in inflammation. Our results clearly demonstrate that sTLT1 is clinically related to the risk factors of CAD. We also showed that binding of sTLT1 with macrophage membrane receptor, FcɣR1 initiates inflammatory signals in macrophages suggesting its critical role in thrombus development and atherosclerosis.

The Influence of Language Context on Repetitive Speech Use in Children With Autism Spectrum Disorder

2020 ◽  
Vol 29 (1) ◽  
pp. 327-334 ◽  
Author(s):  
Allison Gladfelter ◽  
Cassidy VanZuiden
Keyword(s):  
Autism Spectrum Disorder ◽  
Autism Spectrum ◽  
Individual Characteristics ◽  
Receptive Vocabulary ◽  
Spectrum Disorder ◽  
School Age Children ◽  
Social Responsiveness ◽  
Contributing Factors ◽  
Children With Asd ◽  
Language Context

Purpose Although repetitive speech is a hallmark characteristic of autism spectrum disorder (ASD), the contributing factors that influence repetitive speech use remain unknown. The purpose of this exploratory study was to determine if the language context impacts the amount and type of repetitive speech produced by children with ASD. Method As part of a broader word-learning study, 11 school-age children with ASD participated in two different language contexts: storytelling and play. Previously collected language samples were transcribed and coded for four types of repetitive speech: immediate echolalia, delayed echolalia, verbal stereotypy, and vocal stereotypy. The rates and proportions of repetitive speech were compared across the two language contexts using Wilcoxon signed-ranks tests. Individual characteristics were further explored using Spearman correlations. Results The children produced lower rates of repetitive speech during the storytelling context than the play-based context. Only immediate echolalia differed between the two contexts based on rate and approached significance based on proportion, with more immediate echolalia produced in the play-based context than in the storytelling context. There were no significant correlations between repetitive speech and measures of social responsiveness, expressive or receptive vocabulary, or nonverbal intelligence. Conclusions The children with ASD produced less immediate echolalia in the storytelling context than in the play-based context. Immediate echolalia use was not related to social skills, vocabulary, or nonverbal IQ scores. These findings offer valuable insights into better understanding repetitive speech use in children with ASD.

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