scholarly journals Virucidal activity of CPC-containing oral rinses against SARS-CoV-2 variants and are active in the presence of human saliva

2021 ◽  
Author(s):  
Enyia R Anderson ◽  
Edward I Patterson ◽  
Siobham Richards ◽  
Alison K Green ◽  
Sayandip Mukherjee ◽  
...  
Keyword(s):  
Oral Hygiene ◽  
Limit Of Detection ◽  
Cetylpyridinium Chloride ◽  
Human Saliva ◽  
Virucidal Activity ◽  
Physiological Conditions ◽  
Aqueous Conditions ◽  
Virucidal Efficacy

The role of human saliva in aerosol-based transmission of SARS-CoV-2 has highlighted the need to understand the potential of oral hygiene products to inactivate the virus. Here we examined the efficacy of mouthwashes containing cetylpyridinium chloride (CPC) or chlorhexidine (CHX) in inactivating SARS-CoV-2. After 30 seconds contact under standard aqueous conditions CPC mouthwashes achieved a ≥4.0log10 PFU/mL reduction in SARS-CoV-2 (USA-WA1/2020) titres whereas a comparable product containing CHX achieved <2.0log10 PFU/mL reduction. Further testing with CPC mouthwashes demonstrated efficacy against multiple SARS-CoV-2 variants, with inactivation below the limit of detection observed against the Alpha (B.1.1.7), Beta (B.1.35.1) and Gamma (P.1) variants. Virucidal efficacy of CPC mouthwash was also observed in the presence of human saliva with the product delivering ≥4.0log10 PFU/mL reduction in SARS-CoV-2 titres after 30 seconds providing additional evidence for the virucidal efficacy of CPC mouthwashes under simulated physiological conditions. Together these data suggest CPC-based mouthwashes are effective at inactivating SARS-CoV-2 and further supports the use of mouthwash to mitigate the risk of transmission during density procedures.

Involvement of Heme Oxygenase-1 in Neuropsychiatric and Neurodegenerative Diseases

2018 ◽  
Vol 24 (20) ◽  
pp. 2283-2302 ◽  
Author(s):  
Vivian B. Neis ◽  
Priscila B. Rosa ◽  
Morgana Moretti ◽  
Ana Lucia S. Rodrigues
Keyword(s):  
Neurodegenerative Diseases ◽  
Heme Oxygenase ◽  
Therapeutic Potential ◽  
Redox Homeostasis ◽  
Antioxidant Defenses ◽  
Heme Oxygenase 1 ◽  
Physiological Conditions ◽  
And Oxidative Stress ◽  
Defensive Mechanism

Heme oxygenase (HO) family catalyzes the conversion of heme into free iron, carbon monoxide and biliverdin. It possesses two well-characterized isoforms: HO-1 and HO-2. Under brain physiological conditions, the expression of HO-2 is constitutive, abundant and ubiquitous, whereas HO-1 mRNA and protein are restricted to small populations of neurons and neuroglia. HO-1 is an inducible enzyme that has been shown to participate as an essential defensive mechanism for neurons exposed to oxidant challenges, being related to antioxidant defenses in certain neuropathological conditions. Considering that neurodegenerative diseases (Alzheimer’s Disease (AD), Parkinson’s Disease (PD) and Multiple Sclerosis (MS)) and neuropsychiatric disorders (depression, anxiety, Bipolar Disorder (BD) and schizophrenia) are associated with increased inflammatory markers, impaired redox homeostasis and oxidative stress, conditions that may be associated with alterations in HO-levels/activity, the purpose of this review is to present evidence on the possible role of HO-1 in these Central Nervous System (CNS) diseases. In addition, the possible therapeutic potential of targeting brain HO-1 is explored in this review.

Pathophysiology of Thrombosis in Peripheral Artery Disease

2020 ◽  
Vol 18 (3) ◽  
pp. 204-214 ◽  
Author(s):  
Aida Habib ◽  
Giovanna Petrucci ◽  
Bianca Rocca
Keyword(s):  
Vascular Tone ◽  
Platelet Reactivity ◽  
Coagulation Factors ◽  
Peripheral Artery ◽  
Antithrombotic Agents ◽  
Pharmacological Interventions ◽  
Physiological Conditions ◽  
Vasoactive Mediators ◽  
Artery Disease

<P>Under physiological conditions, peripheral arteries release endogenous vascular-protective and antithrombotic agents. Endothelial cells actively synthesize vasoactive mediators, which regulate vascular tone and platelet reactivity thus preventing thrombosis. Atherosclerosis disrupts homeostasis and favours thrombosis by triggering pro-thrombotic responses in the vessels, platelet activation, aggregation as well as vasoconstriction, phenomena that ultimately lead to symptomatic lumen restriction or complete occlusion. <P> In the present review, we will discuss the homeostatic role of arterial vessels in releasing vascular-protective agents, such as nitric oxide and prostacyclin, the role of pro- and anti-thrombotic vascular receptors as well as the contribution of circulating platelets and coagulation factors in triggering the pro-thrombotic response(s). We will discuss the pathological consequences of disrupting the protective pathways in the arteries and the pharmacological interventions along these pathways.</P>

scholarly journals Influence of the Electrolyte Salt Concentration on DNA Detection with Graphene Transistors

Biosensors ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 24
Author(s):  
Agnes Purwidyantri ◽  
Telma Domingues ◽  
Jérôme Borme ◽  
Joana Rafaela Guerreiro ◽  
Andrey Ipatov ◽  
...  
Keyword(s):  
Phosphate Buffer ◽  
Species Interactions ◽  
Field Effect ◽  
Field Effect Transistors ◽  
Limit Of Detection ◽  
Debye Length ◽  
Intermolecular Forces ◽  
Single Layer Graphene ◽  
Dna Adsorption

Liquid-gated Graphene Field-Effect Transistors (GFET) are ultrasensitive bio-detection platforms carrying out the graphene’s exceptional intrinsic functionalities. Buffer and dilution factor are prevalent strategies towards the optimum performance of the GFETs. However, beyond the Debye length (λD), the role of the graphene-electrolytes’ ionic species interactions on the DNA behavior at the nanoscale interface is complicated. We studied the characteristics of the GFETs under different ionic strength, pH, and electrolyte type, e.g., phosphate buffer (PB), and phosphate buffer saline (PBS), in an automatic portable built-in system. The electrostatic gating and charge transfer phenomena were inferred from the field-effect measurements of the Dirac point position in single-layer graphene (SLG) transistors transfer curves. Results denote that λD is not the main factor governing the effective nanoscale screening environment. We observed that the longer λD was not the determining characteristic for sensitivity increment and limit of detection (LoD) as demonstrated by different types and ionic strengths of measuring buffers. In the DNA hybridization study, our findings show the role of the additional salts present in PBS, as compared to PB, in increasing graphene electron mobility, electrostatic shielding, intermolecular forces and DNA adsorption kinetics leading to an improved sensitivity.

scholarly journals The Potential of Nail Mini-Organ Stem Cells in Skin, Nail and Digit Tips Regeneration

2021 ◽  
Vol 22 (6) ◽  
pp. 2864
Author(s):  
Anna Pulawska-Czub ◽  
Tomasz D. Pieczonka ◽  
Paula Mazurek ◽  
Krzysztof Kobielak
Keyword(s):  
Stem Cells ◽  
Critical Role ◽  
Nail Plate ◽  
Molecular Characteristics ◽  
Continuous Growth ◽  
Physiological Conditions ◽  
Morphogenetic Protein ◽  
Slow Cycling ◽  
Bifunctional Properties

Nails are highly keratinized skin appendages that exhibit continuous growth under physiological conditions and full regeneration upon removal. These mini-organs are maintained by two autonomous populations of skin stem cells. The fast-cycling, highly proliferative stem cells of the nail matrix (nail stem cells (NSCs)) predominantly replenish the nail plate. Furthermore, the slow-cycling population of the nail proximal fold (nail proximal fold stem cells (NPFSCs)) displays bifunctional properties by contributing to the peri-nail epidermis under the normal homeostasis and the nail structure upon injury. Here, we discuss nail mini-organ stem cells’ location and their role in skin and nail homeostasis and regeneration, emphasizing their importance to orchestrate the whole digit tip regeneration. Such endogenous regeneration capabilities are observed in rodents and primates. However, they are limited to the region adjacent to the nail’s proximal area, indicating the crucial role of nail mini-organ stem cells in digit restoration. Further, we explore the molecular characteristics of nail mini-organ stem cells and the critical role of the bone morphogenetic protein (BMP) and Wnt signaling pathways in homeostatic nail growth and digit restoration. Finally, we investigate the latest accomplishments in stimulating regenerative responses in regeneration-incompetent injuries. These pioneer results might open up new opportunities to overcome amputated mammalian digits and limbs’ regenerative failures in the future.

scholarly journals TP53-Induced Glycolysis and Apoptosis Regulator (TIGAR) Is Upregulated in Lymphocytes Stimulated with Concanavalin A

2021 ◽  
Vol 22 (14) ◽  
pp. 7436
Author(s):  
Helga Simon-Molas ◽  
Xavier Vallvé-Martínez ◽  
Irene Caldera-Quevedo ◽  
Pere Fontova ◽  
Claudia Arnedo-Pac ◽  
...  
Keyword(s):  
Concanavalin A ◽  
Carbon Flux ◽  
Human Lymphocytes ◽  
Tumor Development ◽  
Pentose Phosphate ◽  
Akt Signaling Pathway ◽  
G6pdh Activity ◽  
Physiological Conditions ◽  
Glucose 6 Phosphate Dehydrogenase

The glycolytic modulator TP53-Inducible Glycolysis and Apoptosis Regulator (TIGAR) is overexpressed in several types of cancer and has a role in metabolic rewiring during tumor development. However, little is known about the role of this enzyme in proliferative tissues under physiological conditions. In the current work, we analysed the role of TIGAR in primary human lymphocytes stimulated with the mitotic agent Concanavalin A (ConA). We found that TIGAR expression was induced in stimulated lymphocytes through the PI3K/AKT pathway, since Akti-1/2 and LY294002 inhibitors prevented the upregulation of TIGAR in response to ConA. In addition, suppression of TIGAR expression by siRNA decreased the levels of the proliferative marker PCNA and increased cellular ROS levels. In this model, TIGAR was found to support the activity of glucose 6-phosphate dehydrogenase (G6PDH), the first enzyme of the pentose phosphate pathway (PPP), since the inhibition of TIGAR reduced G6PDH activity and increased autophagy. In conclusion, we demonstrate here that TIGAR is upregulated in stimulated human lymphocytes through the PI3K/AKT signaling pathway, which contributes to the redirection of the carbon flux to the PPP.

scholarly journals Role of carbon and nitrogen in the improvement of corrosion resistance of new powder metallurgy Co-Cr-Mo alloys

2020 ◽  
Vol 38 (3) ◽  
pp. 273-286 ◽  
Author(s):  
Cristina Garcia-Cabezon ◽  
Celia Garcia-Hernandez ◽  
Maria L. Rodriguez-Mendez ◽  
Gemma Herranz ◽  
Fernando Martin-Pedrosa
Keyword(s):  
Mechanical Properties ◽  
Corrosion Resistance ◽  
Powder Metallurgy ◽  
Nitrogen Content ◽  
Powder Metallurgy Technique ◽  
Carbon And Nitrogen ◽  
Physiological Conditions ◽  
Carbon And Nitrogen Content ◽  
Astm F75

AbstractMicrostructural changes that result in relevant improvements in mechanical properties and electrochemical behavior can be induced using different sintering conditions of ASTM F75 cobalt alloys during their processing using powder metallurgy technique. It has been observed that the increase in carbon and nitrogen content improves corrosion resistance and mechanical properties as long as the precipitation of carbides and nitrides is avoided, thanks to the use of rapid cooling in water after the sintering stage. In addition, the reduction of the particle size of the powder improves hardness and resistance to corrosion in both acid medium with chlorides and phosphate-buffered medium that simulates the physiological conditions for its use as a biomaterial. These results lead to increased knowledge of the role of carbon and nitrogen content in the behavior displayed by the different alloys studied.

scholarly journals Bone remodeling stages under physiological conditions and glucocorticoid in excess: Focus on cellular and molecular mechanisms

2021 ◽  
Vol 12 (2) ◽  
pp. 212-227
Author(s):  
V. V. Povoroznyuk ◽  
N. V. Dedukh ◽  
M. A. Bystrytska ◽  
V. S. Shapovalov
Keyword(s):  
Growth Factors ◽  
Bone Resorption ◽  
Signaling Pathways ◽  
Bone Remodeling ◽  
Molecular Mechanisms ◽  
Signaling Molecules ◽  
Physiological Conditions ◽  
Bone Cell Differentiation ◽  
Repressive Effect

This review provides a rationale for the cellular and molecular mechanisms of bone remodeling stages under physiological conditions and glucocorticoids (GCs) in excess. Remodeling is a synchronous process involving bone resorption and formation, proceeding through stages of: (1) resting bone, (2) activation, (3) bone resorption, (4) reversal, (5) formation, (6) termination. Bone remodeling is strictly controlled by local and systemic regulatory signaling molecules. This review presents current data on the interaction of osteoclasts, osteoblasts and osteocytes in bone remodeling and defines the role of osteoprogenitor cells located above the resorption area in the form of canopies and populating resorption cavities. The signaling pathways of proliferation, differentiation, viability, and cell death during remodeling are presented. The study of signaling pathways is critical to understanding bone remodeling under normal and pathological conditions. The main signaling pathways that control bone resorption and formation are RANK / RANKL / OPG; M-CSF – c-FMS; canonical and non-canonical signaling pathways Wnt; Notch; MARK; TGFβ / SMAD; ephrinB1/ephrinB2 – EphB4, TNFα – TNFβ, and Bim – Bax/Bak. Cytokines, growth factors, prostaglandins, parathyroid hormone, vitamin D, calcitonin, and estrogens also act as regulators of bone remodeling. The role of non-encoding microRNAs and long RNAs in the process of bone cell differentiation has been established. MicroRNAs affect many target genes, have both a repressive effect on bone formation and activate osteoblast differentiation in different ways. Excess of glucocorticoids negatively affects all stages of bone remodeling, disrupts molecular signaling, induces apoptosis of osteocytes and osteoblasts in different ways, and increases the life cycle of osteoclasts. Glucocorticoids disrupt the reversal stage, which is critical for the subsequent stages of remodeling. Negative effects of GCs on signaling molecules of the canonical Wingless (WNT)/β-catenin pathway and other signaling pathways impair osteoblastogenesis. Under the influence of excess glucocorticoids biosynthesis of biologically active growth factors is reduced, which leads to a decrease in the expression by osteoblasts of molecules that form the osteoid. Glucocorticoids stimulate the expression of mineralization inhibitor proteins, osteoid mineralization is delayed, which is accompanied by increased local matrix demineralization. Although many signaling pathways involved in bone resorption and formation have been discovered and described, the temporal and spatial mechanisms of their sequential turn-on and turn-off in cell proliferation and differentiation require additional research.

Bacterial Adhesion to Oral Tissues: A Model for Infectious Diseases

1989 ◽  
Vol 68 (5) ◽  
pp. 750-760 ◽  
Author(s):  
R.J. Gibbons
Keyword(s):  
Conformational Changes ◽  
Oral Hygiene ◽  
Bacterial Adhesion ◽  
Periodontal Diseases ◽  
Bacterial Colonization ◽  
Human Saliva ◽  
Bacterial Attachment ◽  
Poor Oral Hygiene ◽  
Human Teeth ◽  
Mucosal Surfaces

The majority of bacteria which colonize humans display sharp host and tissue tropisms; consequently, relatively little is known about how they initiate colonization on mucosal surfaces. The mouth has a variety of features which have enabled it to serve as a useful model for the discovery of basic principles of host-parasite interactions occurring in mucosal environments. Early studies demonstrated that indigenous bacteria attach to surfaces of the mouth in a highly selective manner; attachment was often observed to correlate with colonization. These studies led to the recognition that bacterial attachment is an essential step for colonization in environments which contain surfaces exposed to a fluid flow. Bacterial adhesion has subsequently grown into a major area of infectious disease research. Many bacteria have been found to possess proteinaceous components, called "adhesins", on their surfaces which bind in a stereochemically specific manner to complementary molecules, or "receptors", on the tissue surface. Adhesins are often lectins which bind to saccharide receptors, but some adhesins are thought to bind to proteinaceous receptors. Studies of components of human saliva, which adsorb to hydroxyapatite (HA) surfaces similar to those of teeth, and promote the attachment of prominent plaque bacteria, have revealed that the acidic proline-rich proteins (PRPs) promote the attachment of several important bacteria. These include strains of Actinomyces viscosus, Bacteroides gingival is, some strains of Streptococcus mutans, and others. The salivary PRP's are a unique family of molecules. However, segments of PRPs are structurally related to collagen. This may be significant, since B. gingivalis and certain cariogenic streptococci bind to collagenous substrata, and such interactions may facilitate their invasion into gingival tissues, or into dentin or cementum, respectively. Another unexpected observation was that although A. viscosus and other bacteria bind avidly to PRPs adsorbed onto apatitic surfaces, they do not interact with PRPs in solution. PRP molecules evidently undergo a conformational change when they adsorb to HA, and adhesins of A. viscosus recognize cryptic segments which are only exposed in adsorbed molecules. This provides the bacteria with a mechanism for efficiently attaching to teeth while suspended in saliva. It also offers a molecular explanation for their sharp tropisms for human teeth. It has proven convenient to refer to such hidden receptors for bacterial adhesins as "cryptitopes" (from cryptic, meaning hidden, and topo, meaning place). The generation of cryptitopes due to conformational changes or because of enzymatic modifications appears to be involved in the colonization of several bacteria on mucosal surfaces. In addition, there is evidence which suggests that elevated levels of neuraminidases and proteases associated with poor oral hygiene and gingivitis may also generate cryptitopes which promote colonization of certain Gram-negative bacteria associated with destructive periodontal diseases. These enzymes concurrently destroy receptors required for attachment of relatively benign species such as S. mitis and S. sanguis. Thus, the elevated levels of enzymes previously reported present in crevicular fluid and saliva of individuals with poor oral hygiene appear to have the potential to modulate bacterial colonization.

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