Alzheimer's disease risk associated with changes in Epstein-Barr virus nuclear antigen 1-specific epitope targeting antibody levels.

Background: Alzheimer's disease (AD) is a neurodegenerative disorder influenced by age, sex, genetic factors, immune alterations, and infections. Multiple lines of evidence suggest that changes in antibody response are linked to AD pathology.

Methods: To elucidate the mechanisms underlying AD development, we investigated antibodies that target autoimmune epitopes using high-resolution epitope microarrays.

A new compound, phomaherbarine A, induces cytolytic reactivation in epstein-barr virus-positive B cell lines.

Epstein-Barr virus (EBV), the first virus found to induce cancer in humans, has been frequently detected in various types of B cell lymphomas. During its latent phase, EBV expresses a limited set of proteins crucial for its persistence. Induction of the lytic phase of EBV has shown promise in the treatment of EBV-associated malignancies.

Variants in the WDR44 WD40-repeat domain cause a spectrum of ciliopathy by impairing ciliogenesis initiation.

WDR44 prevents ciliogenesis initiation by regulating RAB11-dependent vesicle trafficking. Here, we describe male patients with missense and nonsense variants within the WD40 repeats (WDR) of WDR44, an X-linked gene product, who display ciliopathy-related developmental phenotypes that we can model in zebrafish. The patient phenotypic spectrum includes developmental delay/intellectual disability, hypotonia, distinct craniofacial features and variable presence of brain, renal, cardiac and musculoskeletal abnormalities.

Mycoplasma fermentans infection induces human necrotic neuronal cell death via IFITM3-mediated amyloid-β (1-42) deposition.

Mycoplasma fermentans is a proposed risk factor of several neurological diseases that has been detected in necrotic brain lesions of acquired immunodeficiency syndrome patients, implying brain invasiveness. However, the pathogenic roles of M. fermentans in neuronal cells have not been investigated.

Transcriptional regulation of Notch1 by nuclear factor-κB during T cell activation.

Notch1 plays important roles in T cell development and is highly expressed in activated CD4 T cells. However, the underlying mechanism of Notch1 transcription in T cells has not been fully characterized. Therefore, we aimed to determine how Notch1 expression is regulated during the activation of CD4 T cells.

FAM167A is a key molecule to induce BCR-ABL-independent TKI resistance in CML via noncanonical NF-κB signaling activation.

Background: BCR-ABL-independent drug resistance is a barrier to curative treatment of chronic myeloid leukemia (CML). However, the molecular pathways underlying BCR-ABL-independent tyrosine kinase inhibitor (TKI) resistance remain unclear.

Methods: In silico bioinformatic analysis was performed to identify the most active transcription factor and its inducer that contribute to BCR-ABL-independent TKI resistance.

Two Opposing Roles of SARS-CoV-2 RBD-Reactive Antibodies in Pre-Pandemic Plasma Samples From Elderly People in ACE2-Mediated Pseudovirus Infection.

A novel coronavirus designated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged and caused an outbreak of unusual viral pneumonia. Several reports have shown that cross-reactive antibodies against SARS-CoV-2 also exist in people unexposed to this virus. However, the neutralizing activity of cross-reactive antibodies is controversial.

TGF-β Increases MFGE8 Production in Myeloid-Derived Suppressor Cells to Promote B16F10 Melanoma Metastasis.

There is growing evidence that myeloid-derived suppressor cells (MDSCs) are directly involved in all stages leading to metastasis. Many mechanisms for this effect have been proposed, but mechanisms of coregulation between tumor cells and MDSCs remain poorly understood. In this study, we demonstrate that MDSCs are a source of milk fat globule-epidermal growth factor (EGF) factor 8 (MFGE8), which is known to be involved in tumor metastasis.

Integrated Quantitative Phosphoproteomics and Cell-based Functional Screening Reveals Specific Pathological Cardiac Hypertrophy-related Phosphorylation Sites.

Cardiac hypertrophic signaling cascades resulting in heart failure diseases are mediated by protein phosphorylation. Recent developments in mass spectrometry-based phosphoproteomics have led to the identification of thousands of differentially phosphorylated proteins and their phosphorylation sites. However, functional studies of these differentially phosphorylated proteins have not been conducted in a large-scale or high-throughput manner due to a lack of methods capable of revealing the functional relevance of each phosphorylation site.

Discovery of Novel Pyrimidine-Based Capsid Assembly Modulators as Potent Anti-HBV Agents.

Core assembly modulators of viral capsid proteins have been developed as an effective treatment of chronic hepatitis B virus (HBV) infection. In this study, we synthesized novel potent pyrimidine derivatives as core assembly modulators, and their antiviral effects were evaluated in in vitro and in vivo biological experiments. One of the synthesized derivatives, compound (R = MeSO, R = 1-piperidin-4-amine, R = 3-Cl-4-F-aniline) displayed potent inhibitory effects in the in vitro assays (52% inhibition in the protein-based assay at 100 nM and an IC value of 181 nM in the serum HBV DNA quantification assay).

ZIP8 exacerbates collagen-induced arthritis by increasing pathogenic T cell responses.

Zinc is a trace element that is essential for immune responses. Therefore, changes in cellular zinc levels in specific immune cells may influence inflammatory autoimmune diseases, such as rheumatoid arthritis (RA). However, the regulation of zinc mobilization in immune cells and its role in the pathogenesis of RA are not fully understood.

PDK1 Is Required for Maintenance of CD4 Foxp3 Regulatory T Cell Function.

Regulatory T (Treg) cells have an essential role in maintaining immune homeostasis, in part by suppressing effector T cell functions. Phosphoinositide-dependent kinase 1 (PDK1) is a pleiotropic kinase that acts as a key effector downstream of PI3K in many cell types. In T cells, PDK1 has been shown to be critical for activation of NF-κB and AKT signaling upon TCR ligation and is therefore essential for effector T cell activation, proliferation, and cytokine production.

The Functional Roles and Applications of Immunoglobulins in Neurodegenerative Disease.

Natural autoantibodies, immunoglobulins (Igs) that target self-proteins, are common in the plasma of healthy individuals; some of the autoantibodies play pathogenic roles in systemic or tissue-specific autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. Recently, the field of autoantibody-associated diseases has expanded to encompass neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD), with related studies examining the functions of Igs in the central nervous system (CNS). Recent evidence suggests that Igs have various effects in the CNS; these effects are associated with the prevention of neurodegeneration, as well as induction.

Recent insights of T cell receptor-mediated signaling pathways for T cell activation and development.

T cell activation requires extracellular stimulatory signals that are mainly mediated by T cell receptor (TCR) complexes. The TCR recognizes antigens on major histocompatibility complex molecules with the cooperation of CD4 or CD8 coreceptors. After recognition, TCR-induced signaling cascades that propagate signals via various molecules and second messengers are induced.

Comparison of Two Analytical Platforms in Cerebrospinal Fluid Biomarkers for the Classification of Alzheimer's Disease Spectrum with Amyloid PET Imaging.

Background: Cerebrospinal fluid (CSF) amyloid-β1-42 (Aβ1-42), total tau protein (t-Tau), and phosphorylated Tau (p-Tau) are ATN biomarkers for Alzheimer's disease (AD) and reflect pathogenic changes in the brain. CSF biomarkers of AD are considered for inclusion in the diagnostic criteria for research and clinical purposes to reduce the uncertainty of clinical diagnosis and to distinguish among AD stages.

Objective: This study aims to compare two commercially available analytical platforms with respect to accuracy and the potential for early diagnosis of AD.

Development of a mass spectrometric screening assay for hepatitis B virus entry inhibitors.

Sodium taurocholate cotransporting polypeptide (NTCP) involved in bile acid transport in the liver is an entry receptor of hepatitis B virus (HBV). In the present study, we introduce a mass spectrometric screening assay for targeting HBV entry inhibitors that can reduce NTCP transporter activity by employing taurocholic acid (TCA) labeled with stable isotope (2,2,4,4-d-TCA, d-TCA) and NTCP-overexpressing human liver cancer cell lines such as HepG2 and Huh-7. The accuracy and reliability of the proposed mass spectrometric NTCP activity assay have been validated with known HBV inhibitors including cyclosporine A (CsA) and pre-S1 peptide (PreS/2-48 or myrcludex B analog) that suppress the entry of HBV into hepatocytes by targeting NTCP.

SERPINA3 is a key modulator of HNRNP-K transcriptional activity against oxidative stress in HCC.

Most studies about serpin peptidase inhibitor, clade A member 3 (SERPINA3) has been limited to its inhibitory functions and mechanisms. Herein, we report a novel role of SERPINA3 in transcriptional regulation of HCC progression-related genes. Among 19 selected genes through HCC cell isolation system based on telomere length, microarray analyses, and cell-based studies, SERPINA3 was the strongest determinant of increases in telomere length, HCC cell proliferation, survival, migration, and invasion.

Ciclopirox inhibits Hepatitis B Virus secretion by blocking capsid assembly.

Chronic hepatitis B virus (HBV) infection can cause cirrhosis and hepatocellular carcinoma and is therefore a serious public health problem. Infected patients are currently treated with nucleoside/nucleotide analogs and interferon α, but this approach is not curative. Here, we screen 978 FDA-approved compounds for their ability to inhibit HBV replication in HBV-expressing HepG2.

Cerebrospinal Fluid Biomarkers for the Diagnosis of Prodromal Alzheimer's Disease in Amnestic Mild Cognitive Impairment.

Background/aims: Disease-modifying therapy for Alzheimer's disease (AD) has led to a need for biomarkers to identify prodromal AD and very early stage of AD dementia. We aimed to identify the cutoff values of cerebrospinal fluid (CSF) biomarkers for detecting prodromal AD.

Methods: We assessed 56 patients with amnestic mild cognitive impairment (aMCI) who underwent lumbar puncture.