scholarly journals Bactericidal activity of avian complement: a contribution to understand avian-host tropism of Lyme borreliae

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Valerie Sürth ◽  
Isabel Lopes de Carvalho ◽  
Maria Sofia Núncio ◽  
Ana Cláudia Norte ◽  
Peter Kraiczy
Keyword(s):  
Molecular Mechanisms ◽  
Bird Species ◽  
Parus Major ◽  
Columba Livia ◽  
Sensu Stricto ◽  
Avian Host ◽  
Serum Samples ◽  
Host Tropism ◽  
Tick Infection

AbstractComplement has been considered as an important factor impacting the host–pathogen association of spirochetes belonging to the Borrelia burgdorferi sensu lato complex, and may play a role in the spirochete’s ecology. Birds are known to be important hosts for ticks and in the maintenance of borreliae. Recent field surveys and laboratory transmission studies indicated that certain avian species act as reservoir hosts for different Borrelia species. Nevertheless, our current understanding of the molecular mechanisms determining host tropism of Borrelia is still in its fledgling stage. Concerning the role of complement in avian-host tropism, only a few bird species and Borrelia species have been analysed so far. Here, we performed in vitro serum bactericidal assays with serum samples collected from four bird species including the European robin Erithacus rubecula, the great tit Parus major, the Eurasian blackbird Turdus merula, and the racing pigeon Columba livia, as well as four Borrelia species (B. afzelii, B. garinii, B. valaisiana, and B. burgdorferi sensu stricto). From July to September 2019, juvenile wild birds were caught using mist nets in Portugal. Racing pigeons were sampled in a loft in October 2019. Independent of the bird species analysed, all Borrelia species displayed an intermediate serum-resistant or serum-resistant phenotype except for B. afzelii challenged with serum from blackbirds. This genospecies was efficiently killed by avian complement, suggesting that blackbirds served as dead-end hosts for B. afzelii. In summary, these findings suggest that complement contributes in the avian–spirochete–tick infection cycle and in Borrelia-host tropism.

scholarly journals MiR-203 Targets to the 3′-UTR of SLUG to Suppress Cerebral Infarction-Induced Endothelial Cell Growth and Motility

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Yunsong Li ◽  
Wei Bi ◽  
Bing Han ◽  
Tao Yuan ◽  
Long Shi ◽  
...  
Keyword(s):  
Cerebral Infarction ◽  
Molecular Mechanisms ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Critical Role ◽  
Ectopic Expression ◽  
Serum Samples ◽  
Invasion And Migration ◽  
And Migration

Cerebral infarction is one of the leading causes of death worldwide, in which angiogenesis plays a critical role. On the other hand, accumulating evidence has demonstrated that microRNAs (miRNAs) function as key modulators in the formation and progression of cerebral infarction. However, the molecular mechanisms of miRNAs underlying cerebral infarction-associated angiogenesis remain unclear. In the present study, we indicated that the expression of miR-203 was significantly downregulated in serum samples derived from patients with cerebral infarction and in mice brain samples following middle cerebral artery occlusion (MCAO) compared with healthy controls. In vitro, the expression of miR-203 was obviously downregulated in hypoxia-induced human umbilical vein vascular endothelial cells (HUVECs). Functionally, ectopic expression of miR-203 drastically suppressed HUVEC proliferation, invasion, and migration. In addition, SLUG, a zinc finger transcriptional repressor, was identified as a direct target of miR-203 and was negatively correlated with miR-203 expression in MCAO mice and in hypoxia-induced HUVECs. Furthermore, overexpression of SLUG reversed the inhibitory effect of miR-203 on proliferation, invasion, and migration abilities of HUVECs. Taken together, our research provides a novel insight of the miR-203-SLUG axis into cerebral infarction-associated endothelial behaviors and may offer a powerful therapeutic target of cerebral ischemia.

scholarly journals Agricultural area increases the infection risk of free ranging birds to St. Louis encephalitis and West Nile viruses (Flavivirus)

2021 ◽  
Author(s):  
Ana Mansilla ◽  
Juan Grande ◽  
Adrián Diaz
Keyword(s):  
Strong Association ◽  
Bird Species ◽  
Infection Risk ◽  
Agricultural Area ◽  
Avian Host ◽  
Serum Samples ◽  
West Nile ◽  
Forested Area ◽  
Biological Variables ◽  
Free Ranging

Anthropogenic changes affect biological communities of host and vectors driving arbovirus activity. In general, urban and agricultural ecosystems harbor less avian and mosquito diversity than native ecosystems and are dominated by few species. Human activities have led to the emergence / re-emergence of different infectious pathogens particularly arboviruses representing a threat to both public health and biodiversity. Saint Louis encephalitis (SLEV) and West Nile viruses (WNV) are transmitted by Culex spp. mosquitoes as main vectors and several bird species as hosts. With the aim to study the exposure of free-ranging bird communities to SLEV and WNV in Pampean agroecosystems as well as to evaluate the environmental/ biological factors potentially associated we collected and bleed free ranging birds in 12 sites. Serum samples were analyzed by Plaque Reduction Neutralization Test (PRNT) for both viruses. Generalized Linear Mixed Models (GLMM) were performed to analyze the association between environmental / biological variables from each sampled site and avian exposition. A total of 1019 birds were sampled during 2017 - 2019. Overall, we found SLEV NTAb in 60 out of 1019 samples (5.8%) while WNV seroprevalence was 2.1% (21/1019). SLEV and WNV seroprevalence were different among the sampled sites. Agricultural area was positively associated with the SLEV-WNV infection risk for an avian host. Forested area also had a strong association but in a negative way. Our results suggest that open agricultural area increase the infection risk of free ranging birds to SLEV and WNV while forested area diminishes the infection risk maybe through a dilution effect of vector and host communities.

scholarly journals Tocilizumab (TCZ) Decreases Angiogenesis in Rheumatoid Arthritis through its Regulatory Effect on miR-146a-5p and EMMPRIN/CD147

2021 ◽  
Author(s):  
Devy Zisman ◽  
Mirna Safieh ◽  
Elina Simanovich ◽  
Joy Feld ◽  
Amalia Kinarty ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Line ◽  
Molecular Mechanisms ◽  
Tube Formation ◽  
Angiogenic Factors ◽  
Angiogenic Factor ◽  
Serum Samples ◽  
Expression Levels ◽  
Enhanced Expression

Abstract BackgroundAngiogenesis is an important contributor to the development of Rheumatoid arthritis (RA). Tocilizumab (TCZ), an anti-IL-6 receptor antibody, is used in the treatment of RA patients, and has been shown to exert anti-inflammatory effects. However, its effects on angiogenesis are not fully elucidated, and the molecular mechanisms regulating this effect are unknown. MethodsWe evaluated the concentrations of several pro- and anti-angiogenic factors and the expression levels of several microRNA molecules that are associated with RA and angiogenesis in serum samples obtained from 40 RA patients, before and 4 months after the initiation of TCZ treatment. Additionally, we used an in vitro co-culture system of fibroblasts (the HT1080 cell line) and monocytes (the U937 cell line) to explore the mechanisms of TCZ action. ResultsSerum samples from RA patients treated with TCZ exhibited reduced levels of EMMPRIN/CD147, enhanced expression of miR-146a-5p and miR-150-5p, and reduced angiogenesis as was manifested by the reduced number of tube-like structures formed by EaHy926 endothelial cell line. In vitro, the accumulation of the pro-angiogenic factors EMMRPIN, VEGF and MMP-9 in the supernatants was increased by co-culturing the HT1080 fibroblasts and the U937 monocytes, while the accumulation of the anti-angiogenic factor thrombospondin-1 (Tsp-1) and the expression levels of miR-146a-5p were reduced. Transfection of HT1080 cells with the miR-146a-5p mimic, decreased the accumulation of EMMPRIN, VEGF and MMP-9. When EMMPRIN was neutralized with a blocking antibody, supernatants derived from these co-cultures exhibited reduced migration, proliferation and tube formation in functional assays. ConclusionsOur findings implicate miR-146a-5p in the regulation of EMMPRIN and propose that TCZ affects angiogenesis through its effects on EMMRPIN and miR-146a-5p.

scholarly journals Population Densities of Birds Breeding in Urbanized Habitats in the Grabiszyn District in the City of Wrocław

2014 ◽  
Vol 63 (2) ◽  
Author(s):  
Grzegorz Kopij
Keyword(s):  
Bird Species ◽  
Passer Domesticus ◽  
Parus Major ◽  
Columba Livia ◽  
Mapping Method ◽  
City Centre ◽  
Pica Pica ◽  
Breeding Bird ◽  
Passer Montanus ◽  
The City

Abstract Studies were carried out in 2010 by mean of simplified version of the mapping method. The study area (395 ha) was located close to the city centre. It comprised a mosaic of urbanized habitats, with a clear dominance of green areas, such as parks (41.1 ha), gardens, cemeteries and tree clumps. A total of 48 breeding bird species were recorded in the whole study area. The most common (<25 pairs/100 ha) were Passer domesticus, Passer montanus, Sturnus vulgaris, Parus caeruleus, Parus major, Apus apus and Columba livia. Numerous (7-15 pairs/100 ha) were also the following species: Columba palumbus, Turdus pilaris, Sylvia atricapilla, Serinus serinus, Turdus merula and Pica pica. Insectivorous birds were the most common birds constituting 63.3%, and granivorous -32.6% of all pairs recorded. Most birds nested in tree holes (39.3%), in/on buildings (30.2%) and in trees/shrubs (25.6%). Distribution of breeding pairs of 23 bird species was presented on maps. Population trends for 17 species were documented. Rapid increase in numbers of Turdus pilaris, Corvus cornix and Phoenicurus phoenicurus and decrease of Pica pica were recorded.

scholarly journals Differential Role of Passerine Birds in Distribution of Borrelia Spirochetes, Based on Data from Ticks Collected from Birds during the Postbreeding Migration Period in Central Europe

2008 ◽  
Vol 75 (3) ◽  
pp. 596-602 ◽  
Author(s):  
Lenka Dubska ◽  
Ivan Literak ◽  
Elena Kocianova ◽  
Veronika Taragelova ◽  
Oldrich Sychra
Keyword(s):  
Czech Republic ◽  
Urban Areas ◽  
Bird Species ◽  
Parus Major ◽  
Passerine Bird ◽  
Sensu Stricto ◽  
Passerine Birds ◽  
Borrelia Garinii ◽  
The Czech Republic

ABSTRACT Borrelia spirochetes in bird-feeding ticks were studied in the Czech Republic. During the postbreeding period (July to September 2005), 1,080 passerine birds infested by 2,240 Ixodes ricinus subadult ticks were examined. Borrelia garinii was detected in 22.2% of the ticks, Borrelia valaisiana was detected in 12.8% of the ticks, Borrelia afzelii was detected in 1.6% of the ticks, and Borrelia burgdorferi sensu stricto was detected in 0.3% of the ticks. After analysis of infections in which the blood meal volume and the stage of the ticks were considered, we concluded that Eurasian blackbirds (Turdus merula), song thrushes (Turdus philomelos), and great tits (Parus major) are capable of transmitting B. garinii; that juvenile blackbirds and song thrushes are prominent reservoirs for B. garinii spirochetes; that some other passerine birds investigated play minor roles in transmitting B. garinii; and that the presence B. afzelii in ticks results from infection in a former stage. Thus, while B. garinii transmission is associated with only a few passerine bird species, these birds have the potential to distribute millions of Lyme disease spirochetes between urban areas.

scholarly journals POS0613 TOCILIZUMAB DECREASES ANGIOGENESIS IN RHEUMATOID ARTHRITIS THROUGH ITS REGULATORY EFFECT ON EMMPRIN/CD147

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 543.2-543
Author(s):  
D. Zisman ◽  
M. Safieh ◽  
E. Simanovich ◽  
J. Feld ◽  
A. Kinarty ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Culture System ◽  
Molecular Mechanisms ◽  
Serum Levels ◽  
Angiogenic Factors ◽  
Angiogenic Factor ◽  
Serum Samples ◽  
Blocking Antibody ◽  
Endothelial Layer

Background:Angiogenesis is an important contributor to the development of Rheumatoid arthritis (RA). Tocilizumab (TCZ), an anti-IL-6 receptor antibody, is an immunosuppressant used in the treatment of RA patients, but its effects on angiogenesis and the molecular mechanisms regulating new blood vessel formation are not fully elucidated.Objectives:To evaluate the concentrations of pro- and anti-angiogenic factors in serum samples of RA patients, before and after the initiation of TCZ treatment and to explore in an in vitro co-culture system the mechanisms of TCZ action.Methods:We evaluated the concentrations of EMMPRIN, VEGF, MMP-9, IL-6, NGAL, endostatin and thrombospondin-1 (Tsp-1) using commercial ELISA kits from 40 RA patients, before and 4 months after the initiation of TCZ treatment. The levels of secreted EMMPRIN, VEGF MMP-9 and Tsp-1 were measured in an in vitro co-culture system of HT1080 fibroblasts and U937 monocytes with and without addition of anti-EMMPRIN blocking antibody. In the tube formation assay serum samples and supernatnats from the co-cultures were added to endothelial layer. Images were obtained after 6 hours of incubation and the number of closed lumens were counted in two separate fields. In the wound assay, supernatants from the co-cultures, with or without the addition of the anti-EMMPRIN antibody were added to the endothelial layer after scratching. The scratch site area was measured immediately and compared to the area after 24 hours of incubation to assess the distance of cell migration.Results:Study population included 40 RA patients, 33 (82.5%) females, mean age of 57.5±11.1 years, disease duration of 7.7±5.6 years, and 53.9% positive for rheumatoid factor initiating treatment with TCZ. In this patient cohort, 25/40 (62.5%) patients were classified as “responders” according to EULAR criteria.Following 4 mounts of treatment, statistically significant reductions in the levels of EMMPRIN/CD147 (p=0.035), without significant changes in serum levels of MMP-9, VEGF, MMP-3 and MMP-7 and of the anti-angiogenetic factors Tsp-1 and endostatin were found. A statistically significant decrease in the ratio between the pro-angiogenic factor EMMPRIN and the anti-angiogenic factor Tsp-1 that was calculated for each patient 4 months after initiating TCZ was found(p=0.031). The decrease in angiogenesis was manifested by the reduced number of closed lumen tube-like structures formed by EaHy926 endothelial cell line after incubation with serum samples 4 months after initiation of TCZ, relative to the number of closed lumens formed prior to TCZ initiation (p=0.007). The ratio between EMMPRIN and Tsp-1 was significantly reduced in the responding patients versus non-responders (p=0.033), while the levels of VEGF, MMP-9, Tsp-1, and EMMPRIN were unchanged.In vitro, the accumulation of the pro-angiogenic factors EMMRPIN, VEGF and MMP-9 in the supernatants was increased in the co-culture, while the accumulation of the anti-angiogenic factor Tsp-1 was decreased. When EMMPRIN was neutralized with a blocking antibody, supernatants derived from these co-cultures exhibited reduced migration, proliferation, and tube-like structure formation in functional assays.Conclusion:Our findings suggest an important role for EMMPRIN in mediating pro-angiogenic signals in RA patients, with EMMPRIN/Tsp-1 ratio serving as a marker of angiogenesis in RA. When administered to RA patients, TCZ in turn, exerts an anti-angiogenic effect through its regulation of EMMRPIN/CD147 levels.Disclosure of Interests:None declared

scholarly journals Tocilizumab (TCZ) Decreases Angiogenesis in Rheumatoid Arthritis Through Its Regulatory Effect on miR-146a-5p and EMMPRIN/CD147

2021 ◽  
Vol 12 ◽  
Author(s):  
Devy Zisman ◽  
Mirna Safieh ◽  
Elina Simanovich ◽  
Joy Feld ◽  
Amalia Kinarty ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Line ◽  
Molecular Mechanisms ◽  
Tube Formation ◽  
Angiogenic Factors ◽  
Angiogenic Factor ◽  
Serum Samples ◽  
Expression Levels ◽  
Angiogenic Potential

BackgroundAngiogenesis is a major contributor to the development of inflammation during Rheumatoid arthritis (RA), as the vascularization of the pannus provides nutrients and oxygen for the infiltrating immune cells and proliferating synoviocytes. Tocilizumab (TCZ) is an anti-IL-6 receptor antibody that is used in the treatment of RA patients, and has been shown to exert anti-inflammatory effects. However, its effects on angiogenesis are not fully elucidated, and the molecular mechanisms regulating this effect are unknown.MethodsWe evaluated the concentrations of several pro- and anti-angiogenic factors and the expression levels of several microRNA molecules that are associated with RA and angiogenesis in serum samples obtained from 40 RA patients, before and 4 months after the initiation of TCZ treatment. Additionally, we used an in vitro co-culture system of fibroblasts (the HT1080 cell line) and monocytes (the U937 cell line) to explore the mechanisms of TCZ action.ResultsSerum samples from RA patients treated with TCZ exhibited reduced circulating levels of EMMPRIN/CD147, enhanced expression of circulating miR-146a-5p and miR-150-5p, and reduced the angiogenic potential as was manifested by the lower number of tube-like structures that were formed by EaHy926 endothelial cell line. In vitro, the accumulation in the supernatants of the pro-angiogenic factors EMMPRIN, VEGF and MMP-9 was increased by co-culturing the HT1080 fibroblasts and the U937 monocytes, while the accumulation of the anti-angiogenic factor thrombospondin-1 (Tsp-1) and the expression levels of miR-146a-5p were reduced. Transfection of HT1080 cells with the miR-146a-5p mimic, decreased the accumulation of EMMPRIN, VEGF and MMP-9. When we neutralized EMMPRIN with a blocking antibody, the supernatants derived from these co-cultures displayed reduced migration, proliferation and tube formation in the functional assays.ConclusionsOur findings implicate miR-146a-5p in the regulation of EMMPRIN and propose that TCZ affects angiogenesis through its effects on EMMPRIN and miR-146a-5p.

High resolution mapping of nucleic acid containing complexes in vitro and in situ

1996 ◽  
Vol 54 ◽  
pp. 48-49
Author(s):  
D. P. Bazett-Jones ◽  
M. J. Hendzel
Keyword(s):  
Nucleic Acid ◽  
High Resolution ◽  
Transcription Initiation ◽  
Molecular Mechanisms ◽  
Heavy Atom ◽  
Regulation Of Transcription ◽  
High Exposure ◽  
Resolution Mapping ◽  
Tata Sequence

Structural analysis of combinations of nucleosomes and transcription factors on promoter and enhancer elements is necessary in order to understand the molecular mechanisms responsible for the regulation of transcription initiation. Such complexes are often not amenable to study by high resolution crystallographic techniques. We have been applying electron spectroscopic imaging (ESI) to specific problems in molecular biology related to transcription regulation. There are several advantages that this technique offers in studies of nucleoprotein complexes. First, an intermediate level of spatial resolution can be achieved because heavy atom contrast agents are not necessary. Second, mass and stoichiometric relationships of protein and nucleic acid can be estimated by phosphorus detection, an element in much higher proportions in nucleic acid than protein. Third, wrapping or bending of the DNA by the protein constituents can be observed by phosphorus mapping of the complexes. Even when ESI is used with high exposure of electrons to the specimen, important macromolecular information may be provided. For example, an image of the TATA binding protein (TBP) bound to DNA is shown in the Figure (top panel). It can be seen that the protein distorts the DNA away from itself and much of its mass sits off the DNA helix axis. Moreover, phosphorus and mass estimates demonstrate whether one or two TBP molecules interact with this particular promoter TATA sequence.

The research of the molecular mechanisms of endothelial dysfunction in vitro

2019 ◽  
Vol XIV (1) ◽  
Author(s):  
R.E. Kalinin ◽  
I.A. Suchkov ◽  
N.V. Korotkova ◽  
N.D. Mzhavanadze
Keyword(s):  
Endothelial Dysfunction ◽  
Molecular Mechanisms

Natural products from the traditional Moroccan pharmacopoeia: A potential lead for the prevention and treatment of COVID-19

2020 ◽  
Vol 11 (SPL1) ◽  
pp. 1278-1285
Author(s):  
Mohamed Yafout ◽  
Amine Ousaid ◽  
Ibrahim Sbai El Otmani ◽  
Youssef Khayati ◽  
Amal Ait Haj Said
Keyword(s):  
Medicinal Plants ◽  
Plant Extracts ◽  
Molecular Mechanisms ◽  
Scientific Literature ◽  
Treatment Protocol ◽  
World Health ◽  
The World ◽  
Health Organization ◽  
Promising Source

The new SARS-CoV-2 belonging to the coronaviruses family has caused a pandemic affecting millions of people around the world. This pandemic has been declared by the World Health Organization as an international public health emergency. Although several clinical trials involving a large number of drugs are currently underway, no treatment protocol for COVID-19 has been officially approved so far. Here we demonstrate through a search in the scientific literature that the traditional Moroccan pharmacopoeia, which includes more than 500 medicinal plants, is a fascinating and promising source for the research of natural molecules active against SARS-CoV-2. Multiple in-silico and in-vitro studies showed that some of the medicinal plants used by Moroccans for centuries possess inhibitory activity against SARS-CoV or SARS-CoV-2. These inhibitory activities are achieved through the different molecular mechanisms of virus penetration and replication, or indirectly through stimulation of immunity. Thus, the potential of plants, plant extracts and molecules derived from plants that are traditionally used in Morocco and have activity against SARS-CoV-2, could be explored in the search for a preventive or curative treatment against COVID-19. Furthermore, safe plants or plant extracts that are proven to stimulate immunity could be officially recommended by governments as nutritional supplements.

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