Microbiota-derived proteins synergize with IL-23 to drive IL22 production in model type 3 innate lymphoid cells.

Microbiota-induced production of IL-22 by type 3 innate lymphoid cells (ILC3) plays an important role in maintaining intestinal health. Such IL-22 production is driven, in part, by IL-23 produced by gut myeloid cells that have sensed select microbial-derived mediators. The extent to which ILC3 can directly respond to microbial metabolites via IL-22 production is less clear, in part due to the difficulty of isolating and maintaining sufficient numbers of viable ILC3 ex vivo.

Role of Trained Immunity in Heath and Disease.

Purpose Of Review: This review aims to explore the role of immune memory and trained immunity, focusing on how innate immune cells like monocytes, macrophages, and natural killer cells undergo long-term epigenetic and metabolic rewiring. Specifically, it examines the mechanisms by which trained immunity, often triggered by infection or vaccination, could impact cardiac processes and contribute to both protective and pathological responses within the cardiovascular system.

Recent Findings: Recent research demonstrates that vaccination and infection not only activate immune responses in circulating monocytes and tissue macrophages but also affect immune progenitor cells within the bone marrow environment, conferring lasting protection against heterologous infections.

Investigation of the Mesencephalic Astrocyte Derived Neurotrophic Factor-Endoplasmic Reticulum Stress Pathway in Mood Disorders.

Background: Bipolar disorder (BD) has been associated with impaired cellular resilience. Recent studies have shown abnormalities in the unfolded protein response (UPR) in BD. The UPR is the cellular response to endoplasmic reticulum (ER) stress.

Efficacy, safety, and multi-omics analysis of pembrolizumab combined with nab-paclitaxel and platinum as first-line treatment in patients with recurrent or metastatic head and neck squamous cell carcinoma: A single-arm phase 2 study.

Objective: Based on the findings of the KEYNOTE-048 study, pembrolizumab in combination with platinum and fluorouracil is the standard first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). The efficacy and safety of pembrolizumab combined with nab-paclitaxel and platinum in such patients remain unexplored.

Methods: This single-arm phase 2 study enrolled patients with R/M HNSCC who received pembrolizumab (200 mg), nab-paclitaxel (260 mg/m²), and either cisplatin (75 mg/m²) or carboplatin [area under the curve (AUC) 5] every 21 d for up to six cycles, followed by pembrolizumab maintenance therapy.

A simple phylogenetic approach to analyze hypermutated HIV proviruses reveals insights into their dynamics and persistence during antiretroviral therapy.

Hypermutated proviruses, which arise in a single Human Immunodeficiency Virus (HIV) replication cycle when host antiviral APOBEC3 proteins introduce extensive guanine to adenine mutations throughout the viral genome, persist in all people living with HIV receiving antiretroviral therapy (ART). However, hypermutated sequences are routinely excluded from phylogenetic trees because their extensive mutations complicate phylogenetic inference, and as a result, we know relatively little about their within-host evolutionary origins and dynamics. Using >1400 longitudinal single-genome-amplified HIV sequences isolated from six women over a median of 18 years of follow-up-including plasma HIV RNA sequences collected over a median of 9 years between seroconversion and ART initiation, and >500 proviruses isolated over a median of 9 years on ART-we evaluated three approaches for masking hypermutation in nucleotide alignments.

Induction of phospholipase A2 group 4C by HCV infection regulates lipid droplet formation.

Background & Aims: Hepatic steatosis, characterized by lipid accumulation in hepatocytes, is a key diagnostic feature in patients with chronic hepatitis C virus (HCV) infection. This study aimed to clarify the involvement of phospholipid metabolic pathways in the pathogenesis of HCV-induced steatosis.

Methods: The expression and distribution of lipid species in the livers of human liver chimeric mice were analyzed using imaging mass spectrometry.

Panitumumab plus 5-fluorouracil and folinic acid or 5-fluorouracil and folinic acid alone as maintenance therapy in RAS wild-type metastatic colorectal cancer (PanaMa, AIO KRK 0212): final efficacy analysis of a randomised, open-label, phase 2 trial.

Background: The PanaMa trial aimed to compare the efficacy of 5-fluorouracil and folinic acid (FU/FA) ± panitumumab maintenance in untreated wild-type metastatic colorectal cancer (mCRC) patients.

Methods: In this final phase 2 trial analysis, adult mCRC patients responding to six cycles of FU/FA, oxaliplatin and panitumumab were randomized (1:1, open-label) to maintenance of either FU/FA + panitumumab or FU/FA alone. The primary endpoint was superiority of progression-free survival of maintenance (PFS; time from random assignment to progression/death) in favour of FU/FA + panitumumab.

Interpretable Deep-Learning p Prediction for Small Molecule Drugs via Atomic Sensitivity Analysis.

Machine learning (ML) models now play a crucial role in predicting properties essential to drug development, such as a drug's logscale acid-dissociation constant (p). Despite recent architectural advances, these models often generalize poorly to novel compounds due to a scarcity of ground-truth data. Further, these models lack interpretability.

3D Bioprinted Head and Neck Squamous Cell Carcinoma (HNSCC) Model Using Tunicate Derived Nanocellulose (NC) Bioink.

Head and neck squamous cell carcinoma (HNSCC) are invasive solid tumors accounting for high mortality. To improve the clinical outcome, a better understanding of the tumor and its microenvironment (TME) is crucial. Three -dimensional (3D) bioprinting is emerging as a powerful tool for recreating the TME in vitro.

From Isolation to Application: Utilising Phage-Antibiotic Synergy in Murine Bacteremia Model to Combat Multidrug-Resistant Enterococcus faecalis.

Enterococcus species, natural inhabitants of the human gut, have become major causes of life-threatening bloodstream infections (BSIs) and the third most frequent cause of hospital-acquired bacteremia. The rise of high-level gentamicin resistance (HLGR) in enterococcal isolates complicates treatment and revives bacteriophage therapy. This study isolated and identified forty E.

Advances in Preclinical Research of Theranostic Radiopharmaceuticals in Nuclear Medicine.

Theranostics of nuclear medicine refers to the combination of radionuclide imaging and internal irradiation therapy, which is currently a research hotspot and an important direction for the future development of nuclear medicine. Radiopharmaceutical is a vital component of nuclear medicine and serves as one of the fundamental pillars of molecular imaging and precision medicine. At present, a variety of radiopharmaceuticals have been developed for various targets such as fibroblast activation protein (FAP), prostate-specific membrane antigen (PSMA), somatostatin receptor 2 (SSTR2), C-X-C motif chemokine receptor 4 (CXCR4), human epidermal growth factor-2 (HER2), and integrin αvβ, and some of them have been successfully applied in clinical practice.

Circulating MicroRNAs in Patients with Psoriasis Treated with Anti-IL-23: A Cohort Study.

Introduction: Psoriasis is characterized by aberrant keratinocyte activity and immune cell infiltration, driven by immune-mediated pathways. MicroRNAs (miRNAs) play crucial roles in regulating these processes, offering insights into disease mechanisms and therapeutic targets.

Objectives: This study aimed to investigate changes in circulating miRNAs in psoriasis patients undergoing risankizumab therapy, an anti-IL-23 monoclonal antibody, to understand its impact on disease pathogenesis and treatment response.

Proteomic signature of HIV-associated subclinical left atrial remodeling and incident heart failure.

People living with HIV are at higher risk of heart failure and associated left atrial remodeling compared to people without HIV. Mechanisms are unclear but have been linked to inflammation and premature aging. Here we obtain plasma proteomics concurrently with cardiac magnetic resonance imaging in two independent study populations to identify parallels between HIV-related and aging-related immune dysfunction that could contribute to atrial remodeling and clinical heart failure.

A broadly neutralizing antibody against the SARS-CoV-2 Omicron sub-variants BA.1, BA.2, BA.2.12.1, BA.4, and BA.5.

The global spread of Severe Acute Respiratory Syndrome Coronavirus 2. (SARS-CoV-2) and its variant strains, including Alpha, Beta, Gamma, Delta, and now Omicron, pose a significant challenge. With the constant evolution of the virus, Omicron and its subtypes BA.

Viruses and neurodegeneration: a growing concern.

Neurodegenerative diseases (NDDs) cause a progressive loss of neurons. Since NDDs are multifactorial, the precise etiology varies on the basis of the type of disease and patient history. Cohort studies and case studies have demonstrated a potential link between viral infections and the onset or progression of NDDs.

Point of view: Challenges in implementation of new immunotherapies for Alzheimer's disease.

The advancement of disease-modifying treatments (DMTs) for Alzheimer's disease (AD), along with the approval of three amyloid-targeting therapies in the US and several other countries, represents a significant development in the treatment landscape, offering new hope for addressing this once untreatable chronic progressive disease. However, significant challenges persist that could impede the successful integration of this class of drugs into clinical practice. These challenges include determining patient eligibility, appropriate use of diagnostic tools and genetic testing in patient care pathways, effective detection and monitoring of side effects, and improving the healthcare system's readiness by engaging both primary care and dementia specialists.

Examining the effect of direct-from-blood bacterial testing on antibiotic administration and clinical outcomes: a protocol and statistical analysis plan for a pragmatic randomised trial.

Introduction: Patients with suspected bacterial infection frequently receive empiric, broad-spectrum antibiotics prior to pathogen identification due to the time required for bacteria to grow in culture. Direct-from-blood diagnostics identifying the presence or absence of bacteria and/or resistance genes from whole blood samples within hours of collection could enable earlier antibiotic optimisation for patients suspected to have bacterial infections. However, few randomised trials have evaluated the effect of using direct-from-blood bacterial testing on antibiotic administration and clinical outcomes.

Novel Tryptophyllin Peptides from Physalaemus centralis Inhibit Oxidative Stress-Induced Endothelial Dysfunction in Rat Aorta Preparation.

Amphibian skin is a rich source of molecules with biotechnological potential, including the tryptophyllin family of peptides. Here, we report the identification and characterization of two tryptophyllin peptides, FPPEWISR and FPWLLS-NH, from the skin of the Central Dwarf Frog, Physalaemus centralis. These peptides were identified through cDNA cloning and sequence comparison.

Chronic low-dose REV-ERBs agonist SR9009 mitigates constant light-induced weight gain and insulin resistance via adipogenesis modulation.

Background: Obesity and circadian rhythm disruption are significant global health concerns, contributing to an increased risk of metabolic disorders. Both adipose tissue and circadian rhythms play critical roles in maintaining energy homeostasis, and their dysfunction is closely linked to obesity. This study aimed to assess the effects of chronic low-dose SR9009, a REV-ERB ligand, on circadian disruption induced by constant light exposure in mice.

The relationship between patient-reported and clinician-assessed outcome measures in Inclusion body myositis - insights from a retrospective cohort study.

Inclusion body myositis (IBM) is an inflammatory myopathy, characterised by slow progression of weakness, skeletal muscle atrophy, and heterogeneous clinical presentation. This variability in disease progression and presentation complicates tracking of clinical progress and intervention response in clinical trials, presenting challenges in identifying reliable outcome measures. We aimed to identify the most useful suite of clinician-assessed and patient-reported outcome measures (PROMs) for use in clinical practice and trials from a selection of the most commonly used outcome measures in IBM.

CMPK2 promotes NLRP3 inflammasome activation via mtDNA-STING pathway in house dust mite-induced allergic rhinitis.

Background: House dust mite (HDM) is the leading allergen for allergic rhinitis (AR). Although allergic sensitisation by inhaled allergens renders susceptible individuals prone to developing AR, the molecular mechanisms driving this process remain incompletely elucidated.

Objective: This study aimed to elucidate the molecular mechanisms underlying HDM-induced AR.

A multilevel social network approach to studying multiple disease-prevention behaviors.

The effective prevention of many infectious and non-infectious diseases relies on people concurrently adopting multiple prevention behaviors. Individual characteristics, opinion leaders, and social networks have been found to explain why people take up specific prevention behaviors. However, it remains challenging to understand how these factors shape multiple interdependent behaviors.

Inhibited peroxidase activity of peroxiredoxin 1 by palmitic acid exacerbates nonalcoholic steatohepatitis in male mice.

Reactive oxygen species exacerbate nonalcoholic steatohepatitis (NASH) by oxidizing macromolecules; yet how they promote NASH remains poorly understood. Here, we show that peroxidase activity of global hepatic peroxiredoxin (PRDX) is significantly decreased in NASH, and palmitic acid (PA) binds to PRDX1 and inhibits its peroxidase activity. Using three genetic models, we demonstrate that hepatic PRDX1 protects against NASH in male mice.