NaHS alters synaptic plasticity proteins and enhances dendritic arborization to improve cognitive and motor deficits after traumatic brain injury in mice.

Background And Purpose: Traumatic brain injury (TBI) is a complex medical condition affecting people globally. Hydrogen sulfide (HS) is a recently discovered gaseous mediator and is dysregulated in the brain after TBI. Sodium hydrogen sulfide (NaHS), a known donor of HS, is beneficial in various biological processes involving aging and diseases, including injury.

Subphenotypic features of patients with sepsis and ARDS: a multicenter cohort study.

Objectives: Patients with sepsis are often comorbid with acute respiratory distress syndrome (ARDS), and the phenotypic characteristics of pulmonary and non-pulmonary infections leading to ARDS are still unclear. This study aimed to compare the phenotypic characteristics of ARDS resulting from pulmonary infections and other non-site infections and provide better guidance for clinical treatment.

Methods: We conducted a multicenter cohort analysis using data from the Tianjin Medical University General Hospital, Medical Information Mart for Intensive Care-IV (MIMIC-IV), and the electronic intensive care unit (eICU) databases.

Structural insights into the recognition of tetrapyrrole substrates by ancestral class II chelatase CfbA.

Nickel-chelatase CfbA, unlike descendant chelatases, is an ancestral class II chelatase with a symmetric active site architecture. CfbA utilizes sirohydrochlorin (SHC) as a physiological substrate in the biosynthesis of coenzyme F430. CbiX, a structural analog of CfbA, can use uroporphyrin III (UPIII) and uroporphyrin I (UPI) as non-physiological substrates.

Defects in meiosis I contribute to the genesis of androgenetic hydatidiform moles.

To identify novel genes responsible for recurrent hydatidiform moles (HMs), we performed exome sequencing on 75 unrelated patients who were negative for mutations in the known genes. We identified biallelic deleterious variants in 6 genes, FOXL2, MAJIN, KASH5, SYCP2, MEIOB, and HFM1, in patients with androgenetic HMs, including a familial case of 3 affected members. Five of these genes are essential for meiosis I, and their deficiencies lead to premature ovarian insufficiency.

Efficient Neutralizing Antibodies Induction by Human Parvovirus B19 Epitope-Presenting Protein Nanoparticles.

Human parvovirus B19 (B19V) causes fetal hydrops in pregnant women. Despite the significant impact of this virus, effective vaccines remain unclear. In this study, we successfully engineered B19V protein nanoparticles by fusing the N-terminal receptor-binding domain corresponding to 5-80 amino acids of VP1 with two distinct types of self-assembling protein nanoparticles.

Staphylococcal superantigens evoke temporary and reversible T cell anergy, but fail to block the development of a bacterium specific cellular immune response.

Superantigens (sAgs) are bacterial virulence factors that induce a state of immune hyperactivation by forming a bridge between certain subsets of T cell receptor (TCR) β chains on T lymphocytes, and class II major histocompatibility complex (MHC-II) molecules; this cross-linking leads to indiscriminate T cell activation, cytokine storm and toxic shock. Here we show that sAg exposure drives the preferential expansion of naive and central memory T cell subsets, but not effector or resident memory T cells, which instead, hyper release pro-inflammatory cytokines. A targeted therapeutic approach to minimise cytokine release by effector memory T cells attenuated sAg-induced cytokine release.

Clinical progression of Parkinson's disease in the early 21st century: Insights from the accelerating medicine partnership (AMP-PD) data.

Background: Parkinson's disease (PD) therapeutic strategies have evolved since levodopa introduction in mid 1900s. To understand their impact and research gaps, this study delineated the clinical progression of PD in recent years.

Methods: Using Accelerating Medicine Partnership-PD (AMP-PD) data harmonized from seven biomarker discovery studies (2010-2020), we extracted: overall [Schwab and England (S&E), PD Questionnaire (PDQ-39)]; motor [Movement Disorders Society Unified PD Rating Scale (MDS-UPDRS)-II and -III and Hoehn & Yahr (HY)]; and non-motor [MDS-UPDRS-I, University of Pennsylvania Smell Identification Test (UPSIT), Montreal Cognitive Assessment (MoCA), and Epworth Sleepiness Scale (ESS)] scores.

Targeting mitochondrial metabolism by the mitotoxin bromoxib in leukemia and lymphoma cells.

Targeting mitochondrial metabolism represents a promising approach for cancer treatment. Here, we investigated the mitotoxic potential of the polybrominated diphenyl ether bromoxib, a natural compound isolated from the marine sponge Dysidea family. We could show that bromoxib comprised strong cytotoxicity in different leukemia and lymphoma cell lines (such as HL60, HPBALL, Jurkat, K562, KOPTK1, MOLT4, SUPB15 and Ramos), but also in solid tumor cell lines (such as glioblastoma cell lines SJ-GBM2 and TP365MG).

The PI3K-AKT-mTOR axis persists as a therapeutic dependency in KRAS-driven non-small cell lung cancer.

Introduction: KRAS and KRAS inhibitors represent a major translational breakthrough for non-small cell lung cancer (NSCLC) and cancer in general by directly targeting its most mutated oncoprotein. However, resistance to these small molecules has highlighted the need for rational combination partners necessitating a critical understanding of signaling downstream of KRAS mutant isoforms.

Methods: We contrasted tumor development between Kras and Kras genetically engineered mouse models (GEMMs).

ω-Amidase and Its Substrate α-Ketoglutaramate (the α-Keto Acid Analogue of Glutamine) as Biomarkers in Health and Disease.

A large literature exists on the biochemistry, chemistry, metabolism, and clinical importance of the α-keto acid analogues of many amino acids. However, although glutamine is the most abundant amino acid in human tissues, and transamination of glutamine to its α-keto acid analogue (α-ketoglutaramate; KGM) was described more than seventy years ago, little information is available on the biological importance of KGM. Herein, we summarize the metabolic importance of KGM as an intermediate in the glutamine transaminase - ω-amidase (GTωA) pathway for the conversion of glutamine to anaplerotic α-ketoglutarate.

Application of Human Plasma Targeted Lipidomics and Analysis of Toxic Elements to Capture the Metabolic Complexities of Hypothyroidism.

Background: Hypothyroidism (HT) affects millions worldwide and can lead to various lipid disorders. The metabolic complexity and the influence of toxic elements in autoimmune and non-autoimmune HT subtypes are not fully understood. This study aimed to investigate the relationships between plasma lipidome, toxic elements, and clinical classifications of HT in unexposed individuals.

Prevention of cardiometabolic diseases through dietary modifications.

Purpose Of Review: Cardiometabolic diseases (CMDs) increasingly contribute to the cumulative burden of morbidity and mortality worldwide. Here, we reviewed intervention studies using a randomized controlled trial (RCT) design as well as meta-analyses of RCTs aimed at testing the effectiveness of different dietary approaches for CMD prevention.

Recent Findings: Recent studies testing dietary approaches for CMD prevention were summarized narratively, with a focus on interventions based on caloric restriction and fasting, healthy dietary patterns and food-based dietary modifications.

A sex-dependent algorithm including kappa free light chain for multiple sclerosis diagnosis.

Multiple sclerosis (MS) diagnosis includes the presence of restricted oligoclonal bands (OCB) in cerebrospinal fluid (CSF), but it has several limitations, as it is an observer-dependent time-consuming technique and offers a dichotomous result. Thus kappa free light chains (KFLC) have emerged as a quantitative alternative. However, the cut-off values for KFLC have not been well established yet and it is not clear if differences between sexes exist.

Nucleolar Pol II interactome reveals TBPL1, PAF1, and Pol I at intergenic rDNA drive rRNA biogenesis.

Ribosomal DNA (rDNA) repeats harbor ribosomal RNA (rRNA) genes and intergenic spacers (IGS). RNA polymerase (Pol) I transcribes rRNA genes yielding rRNA components of ribosomes. IGS-associated Pol II prevents Pol I from excessively synthesizing IGS non-coding RNAs (ncRNAs) that can disrupt nucleoli and rRNA production.

Editorial: Protein post-translational modifications in the nervous system: from development to disease and ageing.

PTMs are crucial for biological processes contributing to healthy organ function. Protein post-translational modifications (PTMs), such as phosphorylation (P), acetylation (Ac), SUMOylation (SUMO), S-nitrosylation (Nitro), ubiquitination (Ub) and glycosylation (Glyco), affect a wide range of cellular and biological functions as depicted in this cartoon. Perturbations lead to severe consequences for the normal function of the brain and other organs, such as muscle.

Effect of lipid-polymer hybrid nanoparticles on the biophysical function and lateral structure of pulmonary surfactant: Mechanistic in vitro studies.

The interaction between inhaled drug-loaded nanoparticles and pulmonary surfactant (PS) is critical for the efficacy and safety of inhaled nanomedicines. Here, we investigated the effect of small interfering RNA (siRNA)-loaded lipid-polymer hybrid nanoparticles (LPNs), which are designed for treatment of lung inflammation, on the physiological function of PS. By using biophysical in vitro methods we show that siRNA-loaded LPNs affect the biophysical function and lateral structure of PS.

Suppression of non-muscle myosin II boosts T cell cytotoxicity against tumors.

Increasing evidence highlights the importance of immune mechanoregulation in establishing and sustaining tumor-specific cytotoxicity required for desirable immunotherapeutic outcomes. However, the molecular connections between mechanobiological inputs and outputs and the designated immune activities remain largely unclear. Here, we show that partial inhibition of non-muscle myosin II (NM II) augmented the traction force exerted by T cells and potentiated T cell cytotoxicity against tumors.

P-type pilus PapG protein elicits toll-like receptor 2-mediated immune activation during cancer immunotherapy.

The immune activation ability of FimH, an adhesion protein in pili of Escherichia coli (E. coli), has been recently reported. However, studies on the immune activity of PapG, another major pili terminal protein, have not been well explored.

Ruthenium(II) complexes containing PEGylated N-heterocyclic carbene ligands for tunning biocompatibility in the fight against cancer.

A synthetic procedure was designed for the preparation and characterization of Ag and Ru complexes containing NHC ligands functionalized with PEG fragments. Stability studies were conducted to gain insight of the species in water and other solvents like DMSO, or with reagents like imidazole as representative group for histidine amino acid. The presence of Cl atoms instead of H in the 4,5 positions of the N-heterocyclic carbene afforded higher water stability.