scholarly journals Bovine Foamy Virus: Shared and Unique Molecular Features In Vitro and In Vivo

Viruses ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1084 ◽  
Author(s):  
Magdalena Materniak-Kornas ◽  
Juan Tan ◽  
Anke Heit-Mondrzyk ◽  
Agnes Hotz-Wagenblatt ◽  
Martin Löchelt
Keyword(s):  
Animal Studies ◽  
Foamy Virus ◽  
Companion Animals ◽  
Population Level ◽  
Medical Problems ◽  
Bovine Foamy Virus ◽  
Molecular Features ◽  
Unclear Etiology

The retroviral subfamily of Spumaretrovirinae consists of five genera of foamy (spuma) viruses (FVs) that are endemic in some mammalian hosts. Closely related species may be susceptible to the same or highly related FVs. FVs are not known to induce overt disease and thus do not pose medical problems to humans and livestock or companion animals. A robust lab animal model is not available or is a lab animal a natural host of a FV. Due to this, research is limited and often focused on the simian FVs with their well-established zoonotic potential. The authors of this review and their groups have conducted several studies on bovine FV (BFV) in the past with the intention of (i) exploring the risk of zoonotic infection via beef and raw cattle products, (ii) studying a co-factorial role of BFV in different cattle diseases with unclear etiology, (iii) exploring unique features of FV molecular biology and replication strategies in non-simian FVs, and (iv) conducting animal studies and functional virology in BFV-infected calves as a model for corresponding studies in primates or small lab animals. These studies gained new insights into FV-host interactions, mechanisms of gene expression, and transcriptional regulation, including miRNA biology, host-directed restriction of FV replication, spread and distribution in the infected animal, and at the population level. The current review attempts to summarize these findings in BFV and tries to connect them to findings from other FVs.

scholarly journals Bovine Foamy Virus Transactivator BTas Interacts with Cellular RelB To Enhance Viral Transcription

2010 ◽  
Vol 84 (22) ◽  
pp. 11888-11897 ◽  
Author(s):  
Jian Wang ◽  
Juan Tan ◽  
Hongyan Guo ◽  
Qicheng Zhang ◽  
Rui Jia ◽  
...  
Keyword(s):  
Foamy Virus ◽  
Nuclear Factor Κb ◽  
Luciferase Reporter ◽  
Viral Transcription ◽  
Bovine Foamy Virus ◽  
Intracellular Parasites ◽  
Positive Feedback Circuit ◽  
Cellular Machinery

ABSTRACT Viruses are obligate intracellular parasites that depend on cellular machinery for their efficient transcription and replication. In a previous study we reported that bovine foamy virus (BFV) is able to activate the nuclear factor κB (NF-κB) pathway through the action of its transactivator BTas to enhance viral transcription. However, the mechanism used by NF-κB to enhance BFV transcription remains elusive. To address this question, we employed a yeast two-hybrid assay to screen for BTas-interacting proteins. We found that RelB, a member of NF-κB protein family, interacts with BTas. We confirmed the putative RelB-BTas interaction in vitro and in vivo and identified the protein regions responsible for the RelB-BTas interaction. Using a luciferase reporter assay, we next showed that RelB enhances BFV transcription (BTas-induced long terminal repeat [LTR] transactivation) and that this process requires both the localization of the RelB-BTas interaction in the nucleus and the Rel homology domain of RelB. The knockdown of the cellular endogenous RelB protein using small interfering RNA (siRNA) significantly attenuated BTas-induced LTR transcription. The results of chromatin immunoprecipitation (ChIP) analysis showed that endogenous RelB binds to the viral LTR in BFV-infected cells. Together, these results suggest that BFV engages the RelB protein as a cotransactivator of BTas to enhance viral transcription. In addition, our findings indicate that BFV infection upregulates cellular RelB expression through BTas-induced NF-κB activation. Thus, this study demonstrates the existence of a positive-feedback circuit in which BFV utilizes the host's NF-κB pathway through the RelB protein for efficient viral transcription.

scholarly journals A common feature pharmacophore for FDA-approved drugs inhibiting the Ebola virus

F1000Research ◽  
2014 ◽  
Vol 3 ◽  
pp. 277 ◽  
Author(s):  
Sean Ekins ◽  
Joel S. Freundlich ◽  
Megan Coffee
Keyword(s):  
Animal Studies ◽  
Computational Models ◽  
Ebola Virus ◽  
Protein Structures ◽  
Common Features ◽  
Molecular Features ◽  
Approved Drugs ◽  
Fda Approved Drugs

We are currently faced with a global infectious disease crisis which has been anticipated for decades. While many promising biotherapeutics are being tested, the search for a small molecule has yet to deliver an approved drug or therapeutic for the Ebola or similar filoviruses that cause haemorrhagic fever. Two recent high throughput screens published in 2013 did however identify several hits that progressed to animal studies that are FDA approved drugs used for other indications. The current computational analysis uses these molecules from two different structural classes to construct a common features pharmacophore. This ligand-based pharmacophore implicates a possible common target or mechanism that could be further explored. A recent structure based design project yielded nine co-crystal structures of pyrrolidinone inhibitors bound to the viral protein 35 (VP35). When receptor-ligand pharmacophores based on the analogs of these molecules and the protein structures were constructed, the molecular features partially overlapped with the common features of solely ligand-based pharmacophore models based on FDA approved drugs. These previously identified FDA approved drugs with activity against Ebola were therefore docked into this protein. The antimalarials chloroquine and amodiaquine docked favorably in VP35. We propose that these drugs identified to date as inhibitors of the Ebola virus may be targeting VP35. These computational models may provide preliminary insights into the molecular features that are responsible for their activity against Ebola virus in vitro and in vivo and we propose that this hypothesis could be readily tested.

Decellularized bone extracellular matrix in skeletal tissue engineering

2020 ◽  
Vol 48 (3) ◽  
pp. 755-764
Author(s):  
Benjamin B. Rothrauff ◽  
Rocky S. Tuan
Keyword(s):  
Tissue Engineering ◽  
Bone Regeneration ◽  
Tissue Regeneration ◽  
Animal Studies ◽  
Tumor Resection ◽  
Regenerative Capacity ◽  
Skeletal Tissue ◽  
Large Bone

Bone possesses an intrinsic regenerative capacity, which can be compromised by aging, disease, trauma, and iatrogenesis (e.g. tumor resection, pharmacological). At present, autografts and allografts are the principal biological treatments available to replace large bone segments, but both entail several limitations that reduce wider use and consistent success. The use of decellularized extracellular matrices (ECM), often derived from xenogeneic sources, has been shown to favorably influence the immune response to injury and promote site-appropriate tissue regeneration. Decellularized bone ECM (dbECM), utilized in several forms — whole organ, particles, hydrogels — has shown promise in both in vitro and in vivo animal studies to promote osteogenic differentiation of stem/progenitor cells and enhance bone regeneration. However, dbECM has yet to be investigated in clinical studies, which are needed to determine the relative efficacy of this emerging biomaterial as compared with established treatments. This mini-review highlights the recent exploration of dbECM as a biomaterial for skeletal tissue engineering and considers modifications on its future use to more consistently promote bone regeneration.

Modulation of Matrix Metalloproteinases by Plant-Derived Products

2020 ◽  
Vol 20 ◽  
Author(s):  
Nur Najmi Mohamad Anuar ◽  
Nurul Iman Natasya Zulkafali ◽  
Azizah Ugusman
Keyword(s):  
Clinical Trials ◽  
Natural Products ◽  
Matrix Metalloproteinases ◽  
Animal Studies ◽  
Current Knowledge ◽  
In Vitro Models ◽  
In Vivo Studies ◽  
Extracellular Matrix Components

: Matrix metalloproteinases (MMPs) are a group of zinc-dependent metallo-endopeptidase that are responsible towards the degradation, repair and remodelling of extracellular matrix components. MMPs play an important role in maintaining a normal physiological function and preventing diseases such as cancer and cardiovascular diseases. Natural products derived from plants have been used as traditional medicine for centuries. Its active compounds, such as catechin, resveratrol and quercetin, are suggested to play an important role as MMPs inhibitors, thereby opening new insights into their applications in many fields, such as pharmaceutical, cosmetic and food industries. This review summarises the current knowledge on plant-derived natural products with MMP-modulating activities. Most of the reviewed plant-derived products exhibit an inhibitory activity on MMPs. Amongst MMPs, MMP-2 and MMP-9 are the most studied. The expression of MMPs is inhibited through respective signalling pathways, such as MAPK, NF-κB and PI3 kinase pathways, which contribute to the reduction in cancer cell behaviours, such as proliferation and migration. Most studies have employed in vitro models, but a limited number of animal studies and clinical trials have been conducted. Even though plant-derived products show promising results in modulating MMPs, more in vivo studies and clinical trials are needed to support their therapeutic applications in the future.

scholarly journals Occupational Exposure to Carbon Nanotubes and Carbon Nanofibres: More Than a Cobweb

Nanomaterials ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 745
Author(s):  
Enrico Bergamaschi ◽  
Giacomo Garzaro ◽  
Georgia Wilson Jones ◽  
Martina Buglisi ◽  
Michele Caniglia ◽  
...  
Keyword(s):  
Carbon Nanotubes ◽  
Animal Studies ◽  
Chemical Properties ◽  
Biological Behavior ◽  
Cross Sectional ◽  
Carbon Nanofibres ◽  
Material Entity ◽  
Cross Sectional Design

Carbon nanotubes (CNTs) and carbon nanofibers (CNFs) are erroneously considered as singular material entities. Instead, they should be regarded as a heterogeneous class of materials bearing different properties eliciting peculiar biological outcomes both in vitro and in vivo. Given the pace at which the industrial production of CNTs/CNFs is increasing, it is becoming of utmost importance to acquire comprehensive knowledge regarding their biological activity and their hazardous effects in humans. Animal studies carried out by inhalation showed that some CNTs/CNFs species can cause deleterious effects such as inflammation and lung tissue remodeling. Their physico-chemical properties, biological behavior and biopersistence make them similar to asbestos fibers. Human studies suggest some mild effects in workers handling CNT/CNF. However, owing to their cross-sectional design, researchers have been as yet unable to firmly demonstrate a causal relationship between such an exposure and the observed effects. Estimation of acceptable exposure levels should warrant a proper risk management. The aim of this review is to challenge the conception of CNTs/CNFs as a single, unified material entity and prompt the establishment of standardized hazard and exposure assessment methodologies able to properly feeding risk assessment and management frameworks.

scholarly journals Antidiabetic Properties of Naringenin: A Citrus Fruit Polyphenol

Biomolecules ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 99 ◽  
Author(s):  
Danja J. Den Hartogh ◽  
Evangelia Tsiani
Keyword(s):  
Insulin Resistance ◽  
Animal Studies ◽  
Citrus Fruit ◽  
Epidemiological Studies ◽  
Personal Health ◽  
Current Review ◽  
Vegetables And Fruits

Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by insulin resistance and hyperglycemia and is associated with personal health and global economic burdens. Current strategies/approaches of insulin resistance and T2DM prevention and treatment are lacking in efficacy resulting in the need for new preventative and targeted therapies. In recent years, epidemiological studies have suggested that diets rich in vegetables and fruits are associated with health benefits including protection against insulin resistance and T2DM. Naringenin, a citrus flavanone, has been reported to have antioxidant, anti-inflammatory, hepatoprotective, nephroprotective, immunomodulatory and antidiabetic properties. The current review summarizes the existing in vitro and in vivo animal studies examining the anti-diabetic effects of naringenin.

scholarly journals Endothelial-to-Mesenchymal Transition in Human Adipose Tissue Vasculature Alters the Particulate Secretome and Induces Endothelial Dysfunction

2019 ◽  
Vol 39 (10) ◽  
pp. 2168-2191 ◽  
Author(s):  
Bronson A. Haynes ◽  
Li Fang Yang ◽  
Ryan W. Huyck ◽  
Eric J. Lehrer ◽  
Joshua M. Turner ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Endothelial Dysfunction ◽  
Smooth Muscle Actin ◽  
Phenotypic Change ◽  
Alpha Smooth Muscle Actin ◽  
Mesenchymal Transition ◽  
Molecular Features ◽  
Endothelial To Mesenchymal Transition

Objective: Endothelial cells (EC) in obese adipose tissue (AT) are exposed to a chronic proinflammatory environment that may induce a mesenchymal-like phenotype and altered function. The objective of this study was to establish whether endothelial-to-mesenchymal transition (EndoMT) is present in human AT in obesity and to investigate the effect of such transition on endothelial function and the endothelial particulate secretome represented by extracellular vesicles (EV). Approach and Results: We identified EndoMT in obese human AT depots by immunohistochemical co-localization of CD31 or vWF and α-SMA (alpha-smooth muscle actin). We showed that AT EC exposed in vitro to TGF-β (tumor growth factor-β), TNF-α (tumor necrosis factor-α), and IFN-γ (interferon-γ) undergo EndoMT with progressive loss of endothelial markers. The phenotypic change results in failure to maintain a tight barrier in culture, increased migration, and reduced angiogenesis. EndoMT also reduced mitochondrial oxidative phosphorylation and glycolytic capacity of EC. EVs produced by EC that underwent EndoMT dramatically reduced angiogenic capacity of the recipient naïve ECs without affecting their migration or proliferation. Proteomic analysis of EV produced by EC in the proinflammatory conditions showed presence of several pro-inflammatory and immune proteins along with an enrichment in angiogenic receptors. Conclusions: We demonstrated the presence of EndoMT in human AT in obesity. EndoMT in vitro resulted in production of EV that transferred some of the functional and metabolic features to recipient naïve EC. This result suggests that functional and molecular features of EC that underwent EndoMT in vivo can be disseminated in a paracrine or endocrine fashion and may induce endothelial dysfunction in distant vascular beds.

scholarly journals Subinhibitory Antimicrobial Concentrations: A Review of In Vitro and In Vivo Data

1992 ◽  
Vol 3 (4) ◽  
pp. 193-201 ◽  
Author(s):  
George G Zhanel ◽  
Daryl J Hoban ◽  
Godfrey KM Harding
Keyword(s):  
Antimicrobial Activity ◽  
Animal Studies ◽  
Molecular Level ◽  
Bacterial Virulence ◽  
Antibacterial Effects ◽  
Wide Range ◽  
Immune Defences

Antimicrobial activity is not an ‘all or none’ effect. An increase in the rate and extent of antimicrobial action is usually observed over a wide range of antimicrobial concentrations. Subinhibitory antimicrobial concentrations are well known to produce significant antibacterial effects, and various antimicrobials at subinhibitory concentrations have been reported to inhibit the rate of bacterial growth. Bacterial virulence may be increased or decreased by subinhibitory antimicrobial concentrations by changes in the ability of bacteria to adhere to epithelial cells or by alterations in bacterial susceptibility to host immune defences. Animal studies performed in rats, hamsters and rabbits demonstrate decreased bacterial adherence, reduced infectivity and increased survival of animals treated with subinhibitory antimicrobial concentrations compared to untreated controls. The major future role of investigation of subinhibitory antimicrobial concentrations will be to define more fully, at a molecular level, how antimicrobials exert their antibacterial effects.

In vivo assessment of human vaginal oxygen and carbon dioxide levels during and post menses

2005 ◽  
Vol 99 (4) ◽  
pp. 1582-1591 ◽  
Author(s):  
Donna R. Hill ◽  
Marianne E. Brunner ◽  
Deborah C. Schmitz ◽  
Catherine C. Davis ◽  
Janine A. Flood ◽  
...  
Keyword(s):  
Animal Studies ◽  
Pathogenic Bacteria ◽  
Sensor Technology ◽  
Atmospheric Conditions ◽  
Bacterial Virulence Factor ◽  
Carbon Dioxide Levels ◽  
Kinetics Of ◽  
Insertion Process

Previous in vitro and in vivo animal studies showed that O2and CO2concentrations can affect virulence of pathogenic bacteria such as Staphylococcus aureus. The objective of this work was to measure O2and CO2levels in the vaginal environment during tampon wear using newly available sensor technology. Measurements by two vaginal sensors showed a decrease in vaginal O2levels after tampon insertion. These decreases were independent of the type of tampons used and the time of measurement (mid-cycle or during menstruation). These results are not in agreement with a previous study that concluded that oxygenation of the vaginal environment during tampon use occurred via delivery of a bolus of O2during the insertion process. Our measurements of gas levels in menses showed the presence of both O2and CO2in menses. The tampons inserted into the vagina contained O2and CO2levels consistent with atmospheric conditions. Over time during tampon use, levels of O2in the tampon decreased and levels of CO2increased. Tampon absorbent capacity, menses loading, and wear time influenced the kinetics of these changes. Colonization with S. aureus had no effect on the gas profiles during menstruation. Taken collectively, these findings have important implications on the current understanding of gaseous changes in the vaginal environment during menstruation and the potential role(s) they may play in affecting bacterial virulence factor production.

scholarly journals Cardiovascular, carcinogenic and reproductive effects of nicotine exposure: A narrative review of the scientific literature

F1000Research ◽  
2020 ◽  
Vol 8 ◽  
pp. 1586
Author(s):  
Leonie R. Price ◽  
Javier Martinez
Keyword(s):  
Cardiovascular Risk ◽  
Cancer Progression ◽  
Animal Studies ◽  
Scientific Literature ◽  
Human Cancer ◽  
Narrative Review ◽  
Nicotine Exposure ◽  
Health Related

The emergence of new tobacco heating products and electronic nicotine delivery systems (ENDS) is changing the way humans are exposed to nicotine. The purpose of this narrative review is to provide a broad overview of published scientific literature with respect to the effects of nicotine on three key health-related areas: 1) cardiovascular risk, 2) carcinogenesis and 3) reproductive outcomes. These areas are known to be particularly vulnerable to the effects of cigarette smoke, and in addition, nicotine has been hypothesized to play a role in disease pathogenesis. Acute toxicity will also be discussed. The literature to February 2019 suggests that there is no increased cardiovascular risk of nicotine exposure in consumers who have no underlying cardiovascular pathology. There is scientific consensus that nicotine is not a direct or complete carcinogen, however, it remains to be established whether it plays some role in human cancer propagation and metastasis. These cancer progression pathways have been proposed in models in vitro and in transgenic rodent lines in vivo but have not been demonstrated in cases of human cancer. Further studies are needed to determine whether nicotine is linked to decreased fertility in humans. The results from animal studies indicate that nicotine has the potential to act across many mechanisms during fetal development. More studies are needed to address questions regarding nicotine exposure in humans, and this may lead to additional guidance concerning new ENDS entering the market.

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