Bacterial Outer Membrane Vesicles Mediate Cytosolic Localization of LPS and Caspase-11 Activation.

Sensing of lipopolysaccharide (LPS) in the cytosol triggers caspase-11 activation and is central to host defense against Gram-negative bacterial infections and to the pathogenesis of sepsis. Most Gram-negative bacteria that activate caspase-11, however, are not cytosolic, and the mechanism by which LPS from these bacteria gains access to caspase-11 in the cytosol remains elusive. Here, we identify outer membrane vesicles (OMVs) produced by Gram-negative bacteria as a vehicle that delivers LPS into the cytosol triggering caspase-11-dependent effector responses in vitro and in vivo. OMVs are internalized via endocytosis, and LPS is released into the cytosol from early endosomes. The use of hypovesiculating bacterial mutants, compromised in their ability to generate OMVs, reveals the importance of OMVs in mediating the cytosolic localization of LPS. Collectively, these findings demonstrate a critical role for OMVs in enabling the cytosolic entry of LPS and, consequently, caspase-11 activation during Gram-negative bacterial infections.

Gasdermin D Restrains Type I Interferon Response to Cytosolic DNA by Disrupting Ionic Homeostasis.

Inflammasome-activated caspase-1 cleaves gasdermin D to unmask its pore-forming activity, the predominant consequence of which is pyroptosis. Here, we report an additional biological role for gasdermin D in limiting cytosolic DNA surveillance. Cytosolic DNA is sensed by Aim2 and cyclic GMP-AMP synthase (cGAS) leading to inflammasome and type I interferon responses, respectively. We found that gasdermin D activated by the Aim2 inflammasome suppressed cGAS-driven type I interferon response to cytosolic DNA and Francisella novicida in macrophages. Similarly, interferon-ß (IFN-ß) response to F. novicida infection was elevated in gasdermin D-deficient mice. Gasdermin D-mediated negative regulation of IFN-ß occurred in a pyroptosis-, interleukin-1 (IL-1)-, and IL-18-independent manner. Mechanistically, gasdermin D depleted intracellular potassium (K+) via membrane pores, and this K+ efflux was necessary and sufficient to inhibit cGAS-dependent IFN-ß response. Thus, our findings have uncovered an additional interferon regulatory module involving gasdermin D and K+ efflux.

Effect of silver diamine fluoride application on the microtensile bond strength of three commonly used restorative materials in primary teeth: An ultrastructural study.

INTRODUCTION: Caries in primary teeth rapidly advances owing to its thin structure, thereby requiring restoration. However, restorations often fail due to various causes such as secondary caries and reduced microtensile bond strength (µTBS), which calls for the use of antimicrobial agents such as silver diamine fluoride (SDF). AIM: This study aims to measure and analyse the effect of SDF application on the µTBS of three regularly used restorative materials to dentin of primary teeth as well as compare the types of bond failure interfaces under SEM. MATERIALS AND METHODS: The study comprised 60 samples equally divided into six groups among three restorative materials, namely, glass ionomer cement (GIC, Groups I and II), resin-modified glass ionomer cement (RMGIC, Groups III and IV), and composite resin (Groups V and VI) with subdivisions of A and B, where A represented samples with SDF application and B represented samples without SDF application. RESULTS AND OBSERVATIONS: It was observed that µTBS of RMGIC to sound and carious dentin irrespective of SDF application was found to be statistically significant (P < 0.05), and when GIC, RMGIC, and composite resins were compared to both sound and carious dentin irrespective of SDF application, it was statistically significant (P < 0.05). SEM analysis revealed predominantly cohesive failures among all the groups. CONCLUSION: Based on the results, it was concluded that SDF has no adverse effect on the µTBS of GIC, RMGIC, and composite resin to both carious and sound dentin of primary teeth.

In Vitro Assays to Study Inflammasome Activation in Primary Macrophages.

Inflammasomes are multimeric complexes that can sense pathogens and danger signals in the environment. Upon detection of stimuli, caspase-1 is recruited to the inflammasome complex that cleaves and activates pro-inflammatory cytokines, thus initiating a cascade of inflammatory events. While inflammasomes form a crucial component of the host response to pathogens and danger molecules, their unchecked activation can result in the development of autoimmune diseases, metabolic disorders, and pathological outcomes. This chapter describes some assays to detect the measurable outcomes of inflammasome formation and activation. The protocol describes the methods to study the inflammasome pathway using an in vitro assay in primary macrophages. It can be applied to studies investigating the pathway mechanisms and potential therapeutics in the form of inhibitors or activators.

Impact of aquatic microplastics and nanoplastics pollution on ecological systems and sustainable remediation strategies of biodegradation and photodegradation.

The extreme degree of microplastics contamination and its negative impact on ecosystems has become a serious and emerging global concern. Microplastics are mainly generated from products that are used primarily in our everyday lives and are also generated from the fragmentation of larger plastic wastes. It easily penetrates the food chain and, when ingested by aquatic animals or humans, can pose serious health problems. Recently, several technologies have been developed to control the unrestricted spread of microplastics and possibly eradicate them; however, still under investigation. In this review, we have illustrated the types of microplastics, their harmful effect on living things, and the progress to degrade them to protect the environment and life on earth. Several promising and eco-friendly technologies including microbial and enzymatic approaches are enticing to eliminate the microplastics. Also, the photodegradation of microplastics contaminations appeals as a more fascinating approach. The metal oxide-assisted photodegradation of microplastics has also been taken into account. This work presented an impact on the comprehensive research for the effective degradation of different microplastic compositions as well as emerging green approaches for a sustainable environment and a healthier life.

Nikolsky's sign: A pathognomic boon.

Nikolsky's sign has been a very useful diagnostic tool in cases of skin disorders like pemphigus, toxic epidermal necrolysis, etc., The sign is demonstrated when lateral pressure is applied on the border of an intact blister, which results in the dislodgment of the normal epidermis and extension of the blister.

Evaluation of cystic schwannoma of masticator space - A case report.

Schwannoma is a benign neoplasm originating from the neural sheath and occurring in up to 45% of the cases of extracranial neurogenic tumors. Schwannomas of masticator spaces are rare. This article reports the case of an intraoral schwannoma occupying the masseteric and buccal spaces of a 55-year-old woman, for whom detailed imaging investigations were performed, comprising conventional extraoral radiographs, ultrasound, and plain and contrast enhanced magnetic resonance imaging. The lesion was surgically resected.

Pemphigus vulgaris - A report of three cases and review of literature.

Pemphigus vulgaris (PV) is an autoimmune, potentially life-threatening disease causing blisters and erosions of the skin and mucous membranes associated with intraepithelial acantholysis. The underlying mechanism responsible for causing intraepithelial lesions is the binding of immunoglobulin G autoantibodies to desmoglein 3, a transmembrane glycoprotein adhesion molecule present on desmosomes. Histological features comprise intraepithelial cleft and Tzanck cells. Corticosteroids remain the mainstay of the treatment plan. In this article, we have discussed about the diagnosis of three patients suffering from PV, the treatment rendered, and the outcome of the same.

Emerging Insights into Noncanonical Inflammasome Recognition of Microbes.

Inflammasomes are cytosolic multi-molecular complexes that sense intracellular microbial danger signals and metabolic perturbations. Inflammasome activation leads to the activation of caspase-1 and the release of pro-inflammatory cytokines IL-1ß and IL-18 accompanied by cell death. An inflammasome-based surveillance machinery for Gram-negative bacterial infections has been recently discovered. This noncanonical inflammasome relies on sensing the cytosolic presence of lipopolysaccharide of Gram-negative bacteria via inflammatory caspases such as caspase-4, -5, and -11. This review discusses the recent findings related to the mechanism of activation of the noncanonical inflammasome and its biological functions.

Air oxygenation chemistry of 4-TBC catalyzed by chloro bridged dinuclear copper(II) complexes of pyrazole based tridentate ligands: synthesis, structure, magnetic and computational studies.

Four dinuclear bis(µ-Cl) bridged copper(II) complexes, [Cu(2)(µ-Cl)(2)(L(X))(2)](ClO(4))(2) (L(X) = N,N-bis[(3,5-dimethylpyrazole-1-yl)-methyl]benzylamine with X = H(1), OMe(2), Me(3) and Cl(4)), have been synthesized and characterized by the single crystal X-ray diffraction method. In these complexes, each copper(II) center is penta-coordinated with square-pyramidal geometry. In addition to the tridentate L(X) ligand, a chloride ion occupies the last position of the square plane. This chloride ion is also bonded to the neighboring Cu(II) site in its axial position forming an SP-I dinuclear Cu(II) unit that exhibits small intramolecular ferromagnetic interactions and supported by DFT calculations. The complexes 1-3 exhibit methylmonooxygenase (pMMO) behaviour and oxidise 4-tert-butylcatechol (4-TBCH(2)) with molecular oxygen in MeOH or MeCN to 4-tert-butyl-benzoquinone (4-TBQ), 5-methoxy-4-tert-butyl-benzoquinone (5-MeO-4-TBQ) as the major products along with 6,6'-Bu(t)-biphenyl-3,4,3',4'-tetraol and others as minor products. These are further confirmed by ESI- and FAB-mass analyses. A tentative catalytic cycle has been framed based on the mass spectral analysis of the products and DFT calculations on individual intermediates that are energetically feasible.