Metabolic reprogramming and macrophage expansion define ACPA-negative rheumatoid arthritis: insights from single-cell RNA sequencing.

Background: Anti-citrullinated peptide antibodies (ACPA)-negative (ACPA-) rheumatoid arthritis (RA) presents significant diagnostic and therapeutic challenges due to the absence of specific biomarkers, underscoring the need to elucidate its distinctive cellular and metabolic profiles for more targeted interventions.

Methods: Single-cell RNA sequencing data from peripheral blood mononuclear cells (PBMCs) and synovial tissues of patients with ACPA- and ACPA+ RA, as well as healthy controls, were analyzed. Immune cell populations were classified based on clustering and marker gene expression, with pseudotime trajectory analysis, weighted gene co-expression network analysis (WGCNA), and transcription factor network inference providing further insights.

Clinical Analysis of MOG Antibody-Associated Disease Overlapped With Anti-NMDA Receptor Encephalitis: A Long-Term Retrospective Study.

To summarise the clinical characteristics, radiological features, treatments and prognosis of patients with myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) overlapped with NMDA receptor (NMDAR) encephalitis. We retrospectively analysed patients who exhibited dual positivity for MOG antibodies and NMDAR antibodies in serum/CSF from Jan 2018 to Jun 2023. Ten patients with MOGAD and NMDAR encephalitis were enrolled.

Use of esketamine for tracheoscopic drug injection: a randomized controlled trial.

Background: Sufentanil may induce hypotensive bradycardia and other adverse reactions in elderly patients during anesthesia, while esketamine exhibits sedative and analgesic effects with minimal impact on respiration and circulation. The objective of this study was to investigate the impact of these two anesthetics on vital signs in patients undergoing bronchoscopy and lavage under general anesthesia.

Method: This study was a randomized controlled trial with a parallel design.

DL-3-n-Butylphthalide Ameliorates Post-stroke Emotional Disorders by Suppressing Neuroinflammation and PANoptosis.

Post-stroke emotional disorders such as post-stroke anxiety and post-stroke depression are typical symptoms in patients with stroke. They are closely associated with poor prognosis and low quality of life. The State Food and Drug Administration of China has approved DL-3-n-butylphthalide (NBP) as a treatment for ischemic stroke (IS).

Dexmedetomidine attenuates acute stress-impaired learning and memory in mice by maintaining the homeostasis of intestinal flora.

Dexmedetomidine (Dex) has been used in surgery to improve patients' postoperative cognitive function. However, the role of Dex in stress-induced anxiety-like behaviors and cognitive impairment is still unclear. In this study, we tested the role of Dex in anxiety-like behavior and cognitive impairment induced by acute restrictive stress and analyzed the alterations of the intestinal flora to explore the possible mechanism.

P75CD64 neutrophils promote sepsis-induced acute lung injury.

Patients suffering from sepsis-induced acute lung injury (ALI) exhibit a high mortality rate, and their prognosis is closely associated with infiltration of neutrophils into the lungs. In this study, we found a significant elevation of CD64 neutrophils, which highly expressed p75 neurotrophin receptor (p75) in peripheral blood of mice and patients with sepsis-induced ALI. p75CD64 neutrophils were also abundantly expressed in the lung of ALI mice induced by lipopolysaccharide.

Expression of proBDNF/p75 in peripheral blood lymphocytes of patients with sepsis and its impact on lymphocyte differentiation.

Objectives: Sepsis is a life-threatening organ dysfunction caused by the host's imbalanced response to infection. Due to lack of effective treatments, it has always been the difficulty and focus of clinical treatment of sepsis. Studies have shown that pro-brain-derived neurotrophic factor (proBDNF) binds to the high-affinity total neurotrophic factor p75 neurotrophin receptor (p75), which activates downstream signaling cascades and disrupts immunological inflammation and plays an important role in the progression of sepsis.

Mitochondrial and metabolic dysfunction of peripheral immune cells in multiple sclerosis.

Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by the infiltration of inflammatory cells and demyelination of nerves. Mitochondrial dysfunction has been implicated in the pathogenesis of MS, as studies have shown abnormalities in mitochondrial activities, metabolism, mitochondrial DNA (mtDNA) levels, and mitochondrial morphology in immune cells of individuals with MS. The presence of mitochondrial dysfunctions in immune cells contributes to immunological dysregulation and neurodegeneration in MS.

ProBDNF contributed to patrolling monocyte infiltration and renal damage in systemic lupus erythematosus.

Monocyte aberrations have been increasingly recognized as contributors to renal damage in systemic lupus erythematosus (SLE), however, recognition of the underlying mechanisms and modulating strategies is at an early stage. Our studies have demonstrated that brain-derived neurotrophic factor precursor (proBDNF) drives the progress of SLE by perturbing antibody-secreting B cells, and proBDNF facilitates pro-inflammatory responses in monocytes. By utilizing peripheral blood from patients with SLE, GEO database and spontaneous MRL/lpr lupus mice, we demonstrated in the present study that CX3CR1 patrolling monocytes (PMo) numbers were decreased in SLE.

Multiple functions and regulatory network of miR-150 in B lymphocyte-related diseases.

MicroRNAs (miRNAs) play vital roles in the post-transcriptional regulation of gene expression. Previous studies have shown that miR-150 is a crucial regulator of B cell proliferation, differentiation, metabolism, and apoptosis. miR-150 regulates the immune homeostasis during the development of obesity and is aberrantly expressed in multiple B-cell-related malignant tumors.

ProBDNF and its receptors in immune-mediated inflammatory diseases: novel insights into the regulation of metabolism and mitochondria.

Immune-mediated inflammatory diseases (IMIDs) consist of a common and clinically diverse group of diseases. Despite remarkable progress in the past two decades, no remission is observed in a large number of patients, and no effective treatments have been developed to prevent organ and tissue damage. Brain-derived neurotrophic factor precursor (proBDNF) and receptors, such as p75 neurotrophin receptor (p75) and sortilin, have been proposed to mediate intracellular metabolism and mitochondrial function to regulate the progression of several IMIDs.

Hyperactivity of the CD155 immune checkpoint suppresses anti-viral immunity in patients with coronary artery disease.

Pre-existent cardiovascular disease is a risk factor for weak anti-viral immunity, but underlying mechanisms remain undefined. Here, we report that patients with coronary artery disease (CAD) have macrophages (Mϕ) that actively suppress the induction of helper T cells reactive to two viral antigens: the SARS-CoV2 Spike protein and the Epstein-Barr virus (EBV) glycoprotein 350. CAD Mϕ overexpressed the methyltransferase METTL3, promoting the accumulation of N⁶-methyladenosine (m6A) in Poliovirus receptor (CD155) mRNA.

Brain-Derived Neurotrophic Factor Precursor Contributes to a Proinflammatory Program in Monocytes/Macrophages After Acute Myocardial Infarction.

Background The imbalance of monocyte/macrophage polarization toward the preferential proinflammatory phenotype and a lack of normal inflammation resolution are present in acute myocardial infarction (AMI). Our previous study showed that upregulation of brain-derived neurotrophic factor precursor (proBDNF) in M2-like monocytes may contribute to the proinflammatory response in the Stanford type-A acute aortic dissection. The present study aimed to investigate the role of proBDNF signaling in monocytes/macrophages in the progress of AMI.

Aging-associated HELIOS deficiency in naive CD4 T cells alters chromatin remodeling and promotes effector cell responses.

Immune aging combines cellular defects in adaptive immunity with the activation of pathways causing a low-inflammatory state. Here we examined the influence of age on the kinetic changes in the epigenomic and transcriptional landscape induced by T cell receptor (TCR) stimulation in naive CD4 T cells. Despite attenuated TCR signaling in older adults, TCR activation accelerated remodeling of the epigenome and induced transcription factor networks favoring effector cell differentiation.

Mitochondria as disease-relevant organelles in rheumatoid arthritis.

Mitochondria are the controllers of cell metabolism and are recognized as decision makers in cell death pathways, organizers of cytoplasmic signaling networks, managers of cellular stress responses, and regulators of nuclear gene expression. Cells of the immune system are particularly dependent on mitochondrial resources, as they must swiftly respond to danger signals with activation, trafficking, migration, and generation of daughter cells. Analogously, faulty immune responses that lead to autoimmunity and tissue inflammation rely on mitochondria to supply energy, cell building blocks and metabolic intermediates.

The transcription factor RFX5 coordinates antigen-presenting function and resistance to nutrient stress in synovial macrophages.

Tissue macrophages (Mϕ) are essential effector cells in rheumatoid arthritis (RA), contributing to autoimmune tissue inflammation through diverse effector functions. Their arthritogenic potential depends on their proficiency to survive in the glucose-depleted environment of the inflamed joint. Here, we identify a mechanism that links metabolic adaptation to nutrient stress with the efficacy of tissue Mϕ to activate adaptive immunity by presenting antigen to tissue-invading T cells.

Long Non-Coding RNA RFPL3S Functions as a Biomarker of Prognostic and Immunotherapeutic Prediction in Testicular Germ Cell Tumor.

The incidence of testicular germ cell tumor (TGCT) is currently on the rise worldwide, of which 15%-30% of patients have occur recurrence and metastasis. However, clinical methods for diagnosing TGCT and judging its prognosis remained inadequate. In this study, we aimed to explore the possibility of testis-specific long-chain non-coding RNA (lncRNA) Ret finger protein-like 3S (RFPL3S) as a biomarker for TGCT diagnosis, prognosis, and treatment response by reviewing the TGCT gene expression data in Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases.

Up-regulation of proBDNF/p75 signaling in antibody-secreting cells drives systemic lupus erythematosus.

Inappropriate expansion of antibody-secreting cells (ASCs) is typical of systemic lupus erythematosus (SLE), but the regulatory signaling of pathogenic ASCs is unclear. The present study shows that brain-derived neurotrophic factor precursor (proBDNF) and its high-affinity pan-75 neurotrophin receptor (p75) are highly expressed in CD19CD27CD38 ASCs in patients with SLE and in CD19CD44CD138 ASCs in lupus-like mice. The increased proBDNF ASCs were positively correlated with clinical symptoms and higher titers of autoantibodies in SLE.

Mitochondrial aspartate regulates TNF biogenesis and autoimmune tissue inflammation.

Misdirected immunity gives rise to the autoimmune tissue inflammation of rheumatoid arthritis, in which excess production of the cytokine tumor necrosis factor (TNF) is a central pathogenic event. Mechanisms underlying the breakdown of self-tolerance are unclear, but T cells in the arthritic joint have a distinctive metabolic signature of ATP acetyl-CoA proinflammatory effector cells. Here we show that a deficiency in the production of mitochondrial aspartate is an important abnormality in these autoimmune T cells.

Distinct Polarization Dynamics of Microglia and Infiltrating Macrophages: A Novel Mechanism of Spinal Cord Ischemia/Reperfusion Injury.

Purpose: Recent studies indicate that microglia and monocyte-derived macrophages (MDMs) have different roles in diseases such as stroke and spinal cord injury, yet their respective polarized phenotypes and roles remain unclear in spinal cord ischemia/reperfusion injury (SCIRI).

Methods: We established a mouse model of SCIRI by transient aortic occlusion followed by reperfusion. Basso mouse scale (BMS) scores were used to test the locomotor functions.

Injection of Anti-proBDNF Attenuates Hippocampal-Dependent Learning and Memory Dysfunction in Mice With Sepsis-Associated Encephalopathy.

Sepsis-associated encephalopathy (SAE) is a risk factor for cognitive and memory dysfunction; however, the mechanism remains unclear. Brain-derived neurotrophic factor (BDNF) was reported to have a positive effect on cognition and emotion regulation, but the study of its precursor, proBDNF, has been limited. This study aimed to elucidate the effects and associated mechanisms of hippocampal proBDNF in a lipopolysaccharide (LPS)-induced SAE mouse model.

Serum Levels of BDNF in Patients with Adenoma and Colorectal Cancer.

The present study is aimed at examining the serum levels of brain-derived neurotrophic factor (BDNF) and investigating its role in differential diagnosis of colorectal cancer (CRC). . In a Chinese population, we conducted a case-control study to compare the diagnostic performance of serum levels of BDNF and carcinoembryonic antigen (CEA) for CRC.

Brain-derived neurotrophic factor precursor in the immune system is a novel target for treating multiple sclerosis.

Brain-derived neurotrophic factor precursor (proBDNF) is expressed in the central nervous system (CNS) and the immune system. However, the role of proBDNF in the pathogenesis of multiple sclerosis (MS) is unknown. Peripheral blood and post-mortem brain and spinal cord specimens were obtained from multiple sclerosis patients to analyze proBDNF expression in peripheral lymphocytes and infiltrating immune cells in the lesion site.

Hippocampal LASP1 ameliorates chronic stress-mediated behavioral responses in a mouse model of unpredictable chronic mild stress.

Substantial evidence has revealed that abnormalities in synaptic plasticity play important roles during the process of depression. LASP1 (LIM and SH3 domain protein 1), a member of actin-binding proteins, has been shown to be associated with the regulation of synaptic plasticity. However, the role of LASP1 in the regulation of mood is still unclear.