MICROWAVE IRRADIATED GREEN BIGINELLI REACTION†EMPLOYING APPLE, POMEGRANATE AND GRAPE JUICE AS ECO-FRIENDLY REACTION MEDIUM

Objective: The main objective of this work is to explore the utility of apple, pomegranate and grape juice as an eco-friendly reaction medium for microwave assisted green Biginelli reaction.Methods: A series of Biginelli reactions were carried out in various fruit juice medium by employing an equimolar mixture of urea, ethyl acetoacetate and aromatic aldehyde as reactants. All the reactions were performed with the help of microwave irradiation. After successful completion of the reactions, the crude products were isolated, and the pure products were obtained after recrystallization of the crude product from hot ethanol.Results: It was worth to note that all the reactions were completed successfully within few minutes of duration. Pure apple, pomegranate and grape juices were proved to be fruitful as eco-friendly reaction medium for performing microwave-assisted green Biginelli reaction.Conclusion: A green, eco-friendly and cost-effective method was developed for microwave assisted green Biginelli reaction†in apple, pomegranate and grape juice medium. This new method will further motivate the researchers to use more of common fruit juices instead of toxic solvents as reaction medium for multi-component condensation reactions.Keywords: Green synthesis, Fruit Juice, Biginelli reaction, Microwav

Poor Oral Health and its Neurological Consequences: Mechanisms of Porphyromonas gingivalis Involvement in Cognitive Dysfunction

Purpose of review: There is an increasing body of evidence from epidemiology and laboratory investigations on periodontal disease being a risk factor for dementia. In particular, Porphyromonas gingivalis infections in animal models suggest causal associations with Alzheimer’s disease (AD). This review focuses on how P. gingivalis infections promote the incidence of functional loss in AD. Latest findings: The risk of the sporadic form of AD doubles when periodontitis persists for ten or more years. AD differs from other forms of dementia in that the clinical signs together with the presence of amyloid-beta (Aβ) plaques and neurofibrillary tangles must be present at autopsy. P. gingivalis oral infections in mice have demonstrated all of the characteristic pathological and clinical features of AD following infection of the brain. Summary: Multiple factors (inflammation, Aβ oligomers, and bacterial factors) are likely to disrupt neuronal communication channels (synapses) as a plausible explanation for the functional loss

Porphyromonas gingivalis periodontal infection and its putative links with Alzheimer’s disease

Periodontal disease (PD) and Alzheimer’s disease (AD) are inflammatory conditions affecting the global adult population. In the pathogenesis of PD, subgingival complex bacterial biofilm induces inflammation that leads to connective tissue degradation and alveolar bone resorption around the teeth. In health, junctional epithelium seals the gingiva to the tooth enamel, thus preventing bacteria from entering the gingivae. Chronic PD involves major pathogens (Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia) which have an immune armoury that can circumvent host’s immune surveillance to create, and maintain an inflammatory mediator rich, and toxic environment to grow and survive. The neurodegenerative condition, AD is characterised by poor memory and specific hallmark proteins; periodontal pathogens are increasingly being linked with this dementing condition. It is therefore becoming important to understand associations of periodontitis with relevance to late-onset AD. The aim of this review is to discuss the relevance of finding the keystone periodontal pathogen P. gingivalis in AD brains and its plausible contribution to the aetiological hypothesis of this dementing condition

Inflammasome involvement in Alzheimer’s disease

Inflammasomes are responsible for the maturation of pro-inflammatory cytokines such as interleukin (IL)-1β, IL-18 and IL-33 and activation of inflammatory cell death, pyroptosis. They assemble in response to cellular infection and stress or to tissue damage, promote inflammatory reactions and are important in regulating innate immunity particularly by acting as platforms for activation of caspase proteases. They appear to be involved in several pathological processes activated by microbes including Alzheimer’s disease (AD). Best characterized in microbial pathogenesis is the nucleotide-binding domain and leucine-rich repeat (NLR)-protein 3 (NLRP3) inflammasome. AD is a neurodegenerative condition in which the neuropathological hallmarks are the deposition of amyloid beta (Aβ) and hyperphosphorylated tau protein coated neurofibrillary tangles. For decades, the role of the innate immune system in the aetiology of AD was considered less important but the recently discovered inflammatory genes by Genome-wide association studies driving inflammation in this disease has changed this view. Innate immune inflammatory activity in the AD brain can result from the pathological hallmark protein Aβ as well as from specific bacterial infections that tend to possess weak immunostimulatory responses for peripheral blood myeloid cell recruitment to the brain. The weak immunostimulatory activity is a consequence of their immune evasion strategies and survival. In this review we discuss the possibility that inflammasomes, particularly via the NLR family of proteins NLRP3 are involved in the pathogenesis of AD. In addition, we discuss the plausible contribution of specific bacteria playing a role in influencing the activity of the NLRP3 inflammasome to AD progression

Periodontitis, pathogenesis and progression: miRNA-mediated cellular responses to Porphyromonas gingivalis

Porphyromonas gingivalis is considered a keystone pathogen in periodontitis, a disease typically driven by dysbiosis of oral inflammophilic polymicrobial pathobionts. To combat infectious agents, the natural defense response of the host is to switch on inflammatory signaling cascades, whereby miRNA species serve as alternative genetic inhibitory transcriptional endpoints. miRNA profiles from diseased sites differ from those detected in disease free tissues. miRNA profiles could therefore be harnessed as potential diagnostic/prognostic tools. The regulatory role of some miRNA species (miRNA-128, miRNA-146, miRNA-203 and miRNA-584) in the innate immune system, suggests these molecular signatures also have potential in therapy. P. gingivalis associated miRNAs are likely to influence the innate immune response whereas its LPS may affect the nature of host miRNAs and their mRNA targets. This mini review discusses miRNA-dependent transcriptional and regulatory phenomena ensuing immune signaling cascade switch-on with development and progression of periodontitis initiated by P. gingivalis lipopolysaccharide (LPS) exposure

Challenging the Clostridium botulinum toxin type A (BoNT/A) with a selection of microorganisms by culture methods and extended storage of used vials to assess the loss of sterility

In 2002, botulinum toxin type A (BoNT/A) was approved by the US Food and Drug Administration (FDA) for cosmetic use. However, there may be procedural differences between the ways in which a clinician handles, applies and stores the product compared to the suggested guidelines of the manufacturer for handling and storage. To this end vials (N = 12) of BoNT/A were tested for the incidence of microbial contamination followed by challenging the product with a selection of microorganisms by culture methods and by using a calcein release assay to contaminate multi-dose vials at the single concentration used for facial aesthetics. A culture, droplet method was used to count microorganisms challenged with the therapeutic product and to compare viability levels in appropriate controls as well as measuring their lytic properties via an existing cell-free system involving calcein release. Counts of test organisms within the droplets, with the product and the controls without the product were undertaken using Image J software. The result from the incidence of in-vial contamination was inconclusive. Bacterial levels between controls and product challenged groups demonstrated no differences in the growth of viable microorganisms following immediate contact (p = ≥ 0.05). The cell-free calcein release assay demonstrated differences at all time points for low levels of lysis in each case with bacterial lipid extract and were statistically significant (p = 0.011). Although these data appear to correlate with the minimum inhibitory concentration, the additives and vial integrity are also likely to contribute to the maintenance of BoNT/A sterility

Oral Inflammation, Tooth Loss, Risk Factors, and Association with Progression of Alzheimer’s Disease

Periodontitis is a polymicrobial chronic inflammatory disease of tooth-supporting tissues with bacterial etiology affecting all age groups, becoming chronic in a subgroup of older individuals. Periodontal pathogens Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola are implicated in the development of a number of inflammatory pathologies at remote organ sites, including Alzheimer’s disease (AD). The initial inflammatory hypothesis proposed that AD hallmark proteins were the main contributors of central nervous system (CNS) inflammation. This hypothesis is expanding to include the role of infections, lifestyle, and genetic and environmental factors in the pathogenesis of AD. Periodontal disease (PD) typifies a condition that encompasses all of the above factors including pathogenic bacteria. These bacteria not only are the source of low-grade, chronic infection and inflammation that follow daily episodes of bacteremia arising from everyday tasks such as brushing, flossing teeth, chewing food, and during dental procedures, but they also disseminate into the brain from closely related anatomical pathways. The long-term effect of inflammatory mediators, pathogens, and/or their virulence factors, reaching the brain systemically or otherwise would, over time, prime the brain’s own microglia in individuals who have inherent susceptibility traits. Such susceptibilities contribute to inadequate neutralization of invading agents, upon reaching the brain. This has the capacity to create a vicious cycle of sustained local inflammatory milieu resulting in the loss of cytoarchitectural integrity and vital neurons with subsequent loss of function (deterioration in memory). The possible pathways between PD and AD development are considered here, as well as environmental factors that may modulate/exacerbate AD symptoms

An evaluation of the molecular mode of action of trans-resveratrol in the Porphyromonas gingivalis lipopolysaccharide challenged neuronal cell model

Abstract I. Background: Porphyromonas gingivalis triggers a range of innate immune responses in the host that can contribute to the development of periodontitis and dementing diseases including Alzheimer's disease (AD). This study aimed to assess the mode of action of trans-resveratrol in modulating the P. gingivalis lipopolysaccharide (PgLPS) induced metabolic inflammation in the neuronal cell model. II. Methods & Results: Confluent IMR-32 neuroblastoma cells were treated with transresveratrol from Polygonum cuspidatum in the presence or absence of PgLPS. The abundance of messenger ribo-nucleic acid (mRNA) transcript of a panel of 92 genes was quantitatively assessed through targeted transcriptome profiling technique and the biochemical pathways affected were identified through Ingenuity Pathway Analysis. Gene expression analysis revealed that trans-resveratrol down-regulated the mRNA of multiple gene markers including growth factors, transcription factors, kinases, trans-membrane receptors, cytokines and enzymes that were otherwise activated by PgLPS treatement of IMR-32 neuroblastoma cells. Pathway analysis demonstrated that the cellular oxidative stress caused by the activation of phosphoinositide-3-kinase/Akt1 (PI3K/Akt1) pathway that leads to the production of reactive oxygen species (ROS), chronic inflammatory response induced by the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) pathway and nutrient utilization pathways were favourably modulated by trans-resveratrol in the PgLPS challenged IMR-32 cells. III. Conclusions: This study demonstrates the potential of trans-resveratrol as a bioactive compound with multiple modes of intracellular action further supporting its therapeutic application in the neuroinflammatory diseases