mSphere of Influence: Revisiting the central dogma, again!

Dr. Parimal Samir works in the field of host-pathogen interactions. In this mSphere of Influence article, he reflects on how the manuscript entitled " gene synthesis by an antiviral reverse transcriptase" by Samuel Sternberg and colleagues made an impact by reminding him that there is still so much to discover in life sciences.

Investigation of Resin Tag Lengths of Three Commercially Available Pit and Fissure Sealants.

Aim: The aim of this study was to perform a comparative evaluation of the length of resin tags produced by three different types of pit and fissure sealants (Embrace WetBond, Helioseal Clear, and Fuji VII) using scanning electron microscopy.

Materials And Methods: Thirty extracted mandibular premolars were randomly divided into three groups of ten. Each group was treated with one of the sealants - Embrace WetBond, Helioseal Clear, or Fuji VII.

A murine model of post-acute neurological sequelae following SARS-CoV-2 variant infection.

Viral variant is one known risk factor associated with post-acute sequelae of COVID-19 (PASC), yet the pathogenesis is largely unknown. Here, we studied SARS-CoV-2 Delta variant-induced PASC in K18-hACE2 mice. The virus replicated productively, induced robust inflammatory responses in lung and brain tissues, and caused weight loss and mortality during the acute infection.

An Evaluation of Postoperative Pain after Root Canal Instrumentation Using Manual K-files and Kedo-S Rotary files in Primary Molars.

Aim: To determine postoperative pain after root canal instrumentation using manual K-file and rotary Kedo-S files in primary molars.

Material And Method: Thirty-six primary mandibular molars from 4- to 8-year-old children requiring pulpectomy were randomly split into two groups of 18 teeth each, that is, manual file K-file (Group I) and Kedo-S rotary file (Group II). Children's pre- and postoperative pain was assessed using a four-point scale at different time intervals.

A Murine Model of Post-acute Neurological Sequelae Following SARS-CoV-2 Variant Infection.

Viral variant is one known risk factor associated with post-acute sequelae of COVID-19 (PASC), yet the pathogenesis is largely unknown. Here, we studied SARS-CoV-2 Delta variant-induced PASC in K18-hACE2 mice. The virus replicated productively, induced robust inflammatory responses in lung and brain tissues, and caused weight loss and mortality during the acute infection.

TNFR1 signaling converging on FGF14 controls neuronal hyperactivity and sickness behavior in experimental cerebral malaria.

Background: Excess tumor necrosis factor (TNF) is implicated in the pathogenesis of hyperinflammatory experimental cerebral malaria (eCM), including gliosis, increased levels of fibrin(ogen) in the brain, behavioral changes, and mortality. However, the role of TNF in eCM within the brain parenchyma, particularly directly on neurons, remains underdefined. Here, we investigate electrophysiological consequences of eCM on neuronal excitability and cell signaling mechanisms that contribute to observed phenotypes.

Cellular Stress: Modulator of Regulated Cell Death.

Cellular stress response activates a complex program of an adaptive response called integrated stress response (ISR) that can allow a cell to survive in the presence of stressors. ISR reprograms gene expression to increase the transcription and translation of stress response genes while repressing the translation of most proteins to reduce the metabolic burden. In some cases, ISR activation can lead to the assembly of a cytoplasmic membraneless compartment called stress granules (SGs).

Comparing the Effectiveness of Low-Level Laser Therapy and Topical Steroid Therapy Combination Regimen With Routine Topical Steroid Therapy in the Management of Oral Lichen Planus Symptomatic Patients.

Background: For symptomatic oral lichen planus (OLP), a wide range of therapeutic approaches have been suggested. To minimize discomfort and symptoms among individuals with symptomatic OLP, extensive therapy is frequently needed. Therefore, finding a new therapeutic approach that may effectively manage OLP's symptoms and signs while having few adverse effects continues to be a difficult task.

A Correlation between Clinical Classification of Dental Pulp and Periapical Diseases with its Patho Physiology and Pain Pathway.

Background: Dental pain due to pulpal involvement is difficult to diagnose due to the apparent inaccessibility of pulp to the clinical tests, indistinct symptoms, and referred toothache originating from the periodontal tissues. Though we have various clinical classification systems to categorize pulpal diseases, we are yet biased about the exact pathophysiology and pain pathway associated with it. Dental pulp has a complex physiology, and so is its pathophysiology.

SNIP1 and PRC2 coordinate cell fates of neural progenitors during brain development.

Stem cell survival versus death is a developmentally programmed process essential for morphogenesis, sizing, and quality control of genome integrity and cell fates. Cell death is pervasive during development, but its programming is little known. Here, we report that Smad nuclear interacting protein 1 (SNIP1) promotes neural progenitor cell survival and neurogenesis and is, therefore, integral to brain development.

Brain transcriptomics reveal the activation of neuroinflammation pathways during acute infection in mice.

Scrub typhus, an acute febrile illness caused by (), is prevalent in endemic areas with one million new cases annually. Clinical observations suggest central nervous system (CNS) involvement in severe scrub typhus cases. Acute encephalitis syndrome (AES) associated with infection is a major public health problem; however, the underlying mechanisms of neurological disorder remain poorly understood.

The linkage between prevalence of integron I and reduced susceptibility to biocides in MDR isolated from neonates.

Background And Objectives: causes challenging nosocomial fatal infections including neonatal sepsis. Our study aims at clarifying the contribution of integrons in the observed reduced susceptibility of multidrug-resistant (MDR) isolated from septicemic neonates to the clinically used antimicrobial agents and biocides.

Materials And Methods: Eighty-six isolates were collected from Mansoura University Children's Hospital from septicemic neonates.

Comparative Evaluation of Adhesive Bond Strength of Conventional GIC and Cention N to Enamel and Dentin of Primary Teeth: An Study.

Aim: The aim of this study was to evaluate and compare the adhesive bond strength of conventional glass ionomer cement (GIC) and Cention N to the primary enamel and dentin using an accelerated fatigue test.

Materials And Methods: A total of 30 sound human primary molars were collected and were mounted on a metal cylindrical block using acrylic resin, embedding the root up to cemento-enamel junction (CEJ). Proximal box was prepared on both mesial and distal surfaces, one of the cavity was restored with GIC (Type 9) and the other proximal cavity with Cention N.

Estimation of scopoletin from a polyherbal formulation composition using HPLC coupled with fluorescence detector through the concept of Design of Experiment.

High-performance liquid chromatography (HPLC) coupled with a fluorescence detector was used to analyse bioactive phytoconstituent scopoletin from a polyherbal composition derived from the extract prepared from roots of Argyreia nervosa, roots of Withania somnifera, and fruits of Tribulus terrestris. This analytical method was developed as a quality control tool for standardization of the composition to be formulated to enhance spermatogenesis. Chromatographic separation was achieved using Luna® (250 mm × 4.

DEAD/H-Box Helicases in Immunity, Inflammation, Cell Differentiation, and Cell Death and Disease.

DEAD/H-box proteins are the largest family of RNA helicases in mammalian genomes, and they are present in all kingdoms of life. Since their discovery in the late 1980s, DEAD/H-box family proteins have been a major focus of study. They have been found to play central roles in RNA metabolism, gene expression, signal transduction, programmed cell death, and the immune response to bacterial and viral infections.

Integrated stress response restricts macrophage necroptosis.

The integrated stress response (ISR) regulates cellular homeostasis and cell survival following exposure to stressors. Cell death processes such as apoptosis and pyroptosis are known to be modulated by stress responses, but the role of the ISR in necroptosis is poorly understood. Necroptosis is an inflammatory, lytic form of cell death driven by the RIPK3-MLKL signaling axis.

ADAR1 restricts ZBP1-mediated immune response and PANoptosis to promote tumorigenesis.

Cell death provides host defense and maintains homeostasis. Zα-containing molecules are essential for these processes. Z-DNA binding protein 1 (ZBP1) activates inflammatory cell death, PANoptosis, whereas adenosine deaminase acting on RNA 1 (ADAR1) serves as an RNA editor to maintain homeostasis.

Inflammatory Cell Death, PANoptosis, Mediated by Cytokines in Diverse Cancer Lineages Inhibits Tumor Growth.

Resistance to cell death is a hallmark of cancer. Immunotherapy, particularly immune checkpoint blockade therapy, drives immune-mediated cell death and has greatly improved treatment outcomes for some patients with cancer, but it often fails clinically. Its success relies on the cytokines and cytotoxic functions of effector immune cells to bypass the resistance to cell death and eliminate cancer cells.

TLR and IKK Complex-Mediated Innate Immune Signaling Inhibits Stress Granule Assembly.

Cellular stress can induce cytoplasmic ribonucleoprotein complexes called stress granules that allow the cells to survive. Stress granules are also central to cellular responses to infections, in which they can act as platforms for viral sensing or modulate innate immune signaling through pattern recognition receptors. However, the effect of innate immune signaling on stress granules is poorly understood.

DDX3X coordinates host defense against influenza virus by activating the NLRP3 inflammasome and type I interferon response.

Viruses and hosts have coevolved for millions of years, leading to the development of complex host-pathogen interactions. Influenza A virus (IAV) causes severe pulmonary pathology and is a recurrent threat to human health. Innate immune sensing of IAV triggers a complex chain of host responses.

Synergism of TNF-α and IFN-γ Triggers Inflammatory Cell Death, Tissue Damage, and Mortality in SARS-CoV-2 Infection and Cytokine Shock Syndromes.

COVID-19 is characterized by excessive production of pro-inflammatory cytokines and acute lung damage associated with patient mortality. While multiple inflammatory cytokines are produced by innate immune cells during SARS-CoV-2 infection, we found that only the combination of TNF-α and IFN-γ induced inflammatory cell death characterized by inflammatory cell death, PANoptosis. Mechanistically, TNF-α and IFN-γ co-treatment activated the JAK/STAT1/IRF1 axis, inducing nitric oxide production and driving caspase-8/FADD-mediated PANoptosis.

Galactosaminogalactan activates the inflammasome to provide host protection.

Inflammasomes are important sentinels of innate immune defence that are activated in response to diverse stimuli, including pathogen-associated molecular patterns (PAMPs). Activation of the inflammasome provides host defence against aspergillosis, which is a major health concern for patients who are immunocompromised. However, the Aspergillus fumigatus PAMPs that are responsible for inflammasome activation are not known.

Synergism of TNF-α and IFN-γ triggers inflammatory cell death, tissue damage, and mortality in SARS-CoV-2 infection and cytokine shock syndromes.

The COVID-19 pandemic has caused significant morbidity and mortality. Currently, there is a critical shortage of proven treatment options and an urgent need to understand the pathogenesis of multi-organ failure and lung damage. Cytokine storm is associated with severe inflammation and organ damage during COVID-19.