A human oral commensal-mediated protection against Sjögren's syndrome with maintenance of T cell immune homeostasis and improved oral microbiota.

Sjögren's syndrome (SS) is a prevalent systemic autoimmune disease with substantial impacts on women's health worldwide. Although oral Haemophilus parainfluenzae is reduced in SS, its significance remains unclear. This study aimed to elucidate the pathophysiological role of H.

Unravelling molecular mechanisms in atherosclerosis using cellular models and omics technologies.

Despite the discovery and prevalent clinical use of potent lipid-lowering therapies, including statins and PCSK9 inhibitors, cardiovascular diseases (CVD) caused by atherosclerosis remain a large unmet clinical need, accounting for frequent deaths worldwide. The pathogenesis of atherosclerosis is a complex process underlying the presence of modifiable and non-modifiable risk factors affecting several cell types including endothelial cells (ECs), monocytes/macrophages, smooth muscle cells (SMCs) and T cells. Heterogeneous composition of the plaque and its morphology could lead to rupture or erosion causing thrombosis, even a sudden death.

Olaparib enhancing radiosensitization and anti-metastatic effect of oral cancer by targeting IL-17A signal.

Purpose: We tested whether the PARP inhibitor, Olaparib, can effectively enhance radiosensitivity while inhibiting OSCC growth and metastasis in vitro and in vivo. Patient samples were used for survival validation.

Methods: The present study investigated the effect of Olaparib and ionizing radiation (IR) on clonogenic, migratory, and invasive ability in human IR-sensitive (OML1) and IR-resistant (OML1-R) OSCC cell lines.

Structural Deformations in Cucurbit[n]urils: Analysis, Host-Guest Dependence, and Automated Ellipticity Measurements Using ElliptiCB[n].

Cucurbit[n]urils (CB[n]s) are cyclic macrocycles with rich host-guest chemistry. In many cases, guest binding in CB[n]s results in host structural deformations. Unfortunately, measuring such deformations remains a major challenge, with only a handful of manual estimations reported in the literature.

Synthesis, Characterization, and Reactivity of a Synthetic End-On Cobalt(II) Alkyl Persulfide Complex as a Model Platform for Thiolate Persulfidation.

Persulfides (RSS) are ubiquitous source of sulfides (S) in biology, and interactions between RSS and bioinorganic metal centers play critical roles in biological hydrogen sulfide (HS) biogenesis, signaling, and catabolism. Here, we report the use of contact-ion stabilized [Na(15-crown-5)][BuSS] () as a simple synthon to access rare metal alkyl persulfide complexes and to investigate the reactivity of RSS with transition metal centers to provide insights into metal thiolate persulfidation, including the fundamental difference between alkyl persulfides and alkyl thiolates. Reaction of with [Co(TPA)(OTf)] afforded the η-alkyl persulfide complex [Co(TPA)(SSBu)] (), which was characterized by X-ray crystallography, UV-vis spectroscopy, and Raman spectroscopy.

Activity-Based Fluorescent Probes for Hydrogen Sulfide and Related Reactive Sulfur Species.

Hydrogen sulfide (HS) is not only a well-established toxic gas but also an important small molecule bioregulator in all kingdoms of life. In contemporary biology, HS is often classified as a "gasotransmitter," meaning that it is an endogenously produced membrane permeable gas that carries out essential cellular processes. Fluorescent probes for HS and related reactive sulfur species (RSS) detection provide an important cornerstone for investigating the multifaceted roles of these important small molecules in complex biological systems.

Integrative transcriptomic and genomic analyses unveil the IFI16 variants and expression as MASLD progression markers.

Background And Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a broad and continuous spectrum of liver diseases ranging from fatty liver to steatohepatitis. The intricate interactions of genetic, epigenetic, and environmental factors in the development and progression of MASLD remain elusive. Here, we aimed to achieve an integrative understanding of the genomic and transcriptomic alterations throughout the progression of MASLD.

Identification of signature gene set as highly accurate determination of metabolic dysfunction-associated steatotic liver disease progression.

Background/aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by fat accumulation in the liver. MASLD encompasses both steatosis and MASH. Since MASH can lead to cirrhosis and liver cancer, steatosis and MASH must be distinguished during patient treatment.

Major adverse cardiovascular events in advanced-stage lung cancer: a multicenter cohort study.

Background: Lung cancers are common worldwide. First-line targeted therapy and chemotherapy are both standard treatments in the current guidelines. With the development of new anticancer therapy, the lifespan of patients with late-stage lung cancer has increased.

Ola1p trafficking indicates an interaction network between mitochondria, lipid droplets, and stress granules in times of stress.

Protein aggregates arise naturally under normal physiological conditions, but their formation is accelerated by age or stress-induced protein misfolding. When the stressful event dissolves, these aggregates are removed by mechanisms, such as aggrephagy, chaperone-mediated autophagy, refolding attempts, or the proteasome. It was recently shown that mitochondria in yeast cells may support these primarily cytosolic processes.

From Cardiorenal Syndrome to Chronic Cardiovascular and Kidney Disorder: A Conceptual Transition.

The association between cardiac and kidney dysfunction has received attention over the past two decades. A putatively unique syndrome, the cardiorenal syndrome, distinguishing five subtypes on the basis of the chronology of cardiac and kidney events, has been widely adopted. This review discusses the methodologic and practical problems inherent to the current classification of cardiorenal syndrome.

Advances and Opportunities in HS Measurement in Chemical Biology.

Hydrogen sulfide (HS) is an important biological mediator across all kingdoms of life and plays intertwined roles in various disciplines, ranging from geochemical cycles to industrial processes. A common need across these broad disciplines is the ability to detect and measure HS in complex sample environments. This Perspective focuses on key advances and opportunities for HS detection and quantification that are relevant to chemical biology.

A class-specific effect of dysmyelination on the excitability of hippocampal interneurons.

The role of myelination for axonal conduction is well-established in projection neurons but little is known about its significance in GABAergic interneurons. Myelination is discontinuous along interneuron axons and the mechanisms controlling myelin patterning and segregation of ion channels at the nodes of Ranvier have not been elucidated. Protein 4.

Distinct long-term disease activity trajectories differentiate early on treatment with etanercept in both rheumatoid arthritis and spondylarthritis patients: a prospective cohort study.

To characterize disease activity trajectories and compare long-term drug retention between rheumatoid (RA) and spondylarthritis (SpA) patients initiating tumor necrosis factor inhibitor (TNFi) treatment (etanercept). Prospective observational study of RA, axial (AxSpA) and peripheral SpA (PerSpA) patients initiating etanercept during 2004-2020. Kaplan-Meier plots were used for drug retention comparisons and multivariable Cox regression models for predictors of discontinuation.

Measuring the Impact of Genetic Heterogeneity and Chromosomal Inversions on the Efficacy of CRISPR-Cas9 Gene Drives in Different Strains of .

The human malaria vector is becoming increasingly resistant to insecticides, spurring the development of genetic control strategies. CRISPR-Cas9 gene drives can modify a population by creating double-stranded breaks at highly specific targets, triggering copying of the gene drive into the cut site ("homing"), ensuring its inheritance. The DNA repair mechanism responsible requires homology between the donor and recipient chromosomes, presenting challenges for the invasion of laboratory-developed gene drives into wild populations of target species species complex, which show high levels of genome variation.

Understanding Reactive Sulfur Species through P/S Synergy.

We investigated the differential oxidative and nucleophilic chemistry of reactive sulfur and oxygen anions (SSNO, SNO, NO, S, and HS) using the simple reducing electrophile PPhCl. In the case of SSNO reacting with PPhCl, a complex mixture of mono and diphosphorus products is formed exclusively in the P(V) oxidation state. We found that the phosphine stoichiometry dictates selectivity for oxidation to P=S/P=O products or transformation to P species.

The Aging Enteric Nervous System.

The gut and the brain communicate via the nervous system, hormones, microbiota-mediated substances, and the immune system. These intricate interactions have led to the term "gut-brain axis". Unlike the brain-which is somewhat protected-the gut is exposed to a variety of factors throughout life and, consequently, might be either more vulnerable or better adapted to respond to these challenges.

Taming the Dichalcogenides: Isolation, Characterization, and Reactivity of Elusive Perselenide, Persulfide, Thioselenide, and Selenosulfide Anions.

Reactive sulfur species (RSS) and reactive selenium species (RSeS) play integral roles in hydrogen sulfide (HS) and hydrogen selenide (HSe) biological signaling pathways, and dichalcogenide anions are proposed transient intermediates that facilitate a variety of biochemical transformations. Herein we report the selective synthesis, isolation, spectroscopic and structural characterization, and fundamental reactivity of persulfide (RSS), perselenide (RSeSe), thioselenide (RSSe), and selenosulfide (RSeS) anions. The isolated chalcogenides do not rely on steric protection for stability and have steric profiles analogous to cysteine (Cys).

Solubilization of elemental sulfur by surfactants promotes reduction to HS by thiols.

Elemental sulfur (S) may contribute to sulfane sulfur (S) storage in biological systems. We demonstrate that surfactants can solubilize S in water and promote S reduction to HS by thiols. Moreover, anionic and cationic surfactants interact differently with intermediate S carriers, highlighting how specific hydrophobic microenvironments impact reactive sulfur species.

Innate Immunity System in Patients With Cardiovascular and Kidney Disease.

With a global burden of 844 million, chronic kidney disease (CKD) is now considered a public health priority. Cardiovascular risk is pervasive in this population, and low-grade systemic inflammation is an established driver of adverse cardiovascular outcomes in these patients. Accelerated cellular senescence, gut microbiota-dependent immune activation, posttranslational lipoprotein modifications, neuroimmune interactions, osmotic and nonosmotic sodium accumulation, acute kidney injury, and precipitation of crystals in the kidney and the vascular system all concur in determining the unique severity of inflammation in CKD.