Anti-ZSCAN1 Autoantibodies Are a Feasible Diagnostic Marker for ROHHAD Syndrome Not Associated with a Tumor.

Recent studies have reported the presence of autoantibodies against zinc finger and SCAN domain-containing protein 1 (ZSCAN1) in the sera of patients with rapid-onset obesity with hypoventilation, hypothalamic and autonomic dysregulation (ROHHAD) syndrome associated with neuroendocrine tumors, suggesting immunologic and paraneoplastic processes as the pathologic underpinnings. Moreover, several hypothalamic regions, including the subfornical organ (SFO), were reported to exhibit antibody reactivity in a patient with ROHHAD syndrome not associated with a tumor. Whether ROHHAD syndrome not associated with a tumor is associated with anti-ZSCAN1 autoantibodies remains unclear.

Autoantibodies to nuclear valosin-containing protein-like protein: systemic sclerosis-specific antibodies revealed by in vitro human proteome.

Objectives: To identify and characterize undescribed systemic sclerosis (SSc)-specific autoantibodies targeting nucleolar antigens and to assess their clinical significance.

Methods: We conducted proteome-wide autoantibody screening (PWAS) against serum samples from SSc patients with nucleolar patterned anti-nuclear antibodies (NUC-ANAs) of specific antibodies (Abs) unknown, utilizing wet protein arrays fabricated from in vitro human proteome. Controls included SSc patients with already-known SSc-specific autoantibodies, patients with other connective tissue diseases and healthy subjects.

The Autoantibody Array Assay: A Novel Autoantibody Detection Method.

Systemic sclerosis (SSc) and dermatomyositis (DM) are autoimmune collagen diseases. Specific autoantibodies are known to be involved in their pathogeneses, each presenting with a different clinical manifestation. Although immunoprecipitation is the gold standard method for detecting autoantibodies, it is difficult to perform in all cases owing to the use of radioisotopes.

Comprehensive autoantibody profiling in systemic autoimmunity by a highly-sensitive multiplex protein array.

Comprehensive autoantibody evaluation is essential for the management of autoimmune disorders. However, conventional methods suffer from poor sensitivity, low throughput, or limited availability. Here, using a proteome-wide human cDNA library, we developed a novel multiplex protein assay (autoantibody array assay; A-Cube) covering 65 antigens of 43 autoantibodies that are associated with systemic sclerosis (SSc) and polymyositis/dermatomyositis (PM/DM).

LncRNA induces p53 degradation by interfering with the interaction between p53 and the SART3-USP15 complex.

Mammalian genomes encode large number of long noncoding RNAs (lncRNAs) that play key roles in various biological processes, including proliferation, differentiation, and stem cell pluripotency. Recent studies have addressed that some lncRNAs are dysregulated in human cancers and may play crucial roles in tumor development and progression. Here, we show that the lncRNA is required for the proliferation and tumorigenicity of colon cancer cells with wild-type p53.

Significance of anti-transcobalamin receptor antibodies in cutaneous arteritis revealed by proteome-wide autoantibody screening.

Cutaneous arteritis (CA) is a single-organ vasculitis that exclusively affects the small to medium-sized arteries of the skin. Diagnosis depends on a histological investigation with skin biopsy, which could be burdensome for both patients and clinicians. Moreover, the pathogenesis of CA remains unstudied, and treatment has not yet been established.

HOXB7 induces STAT3-mediated transformation and lung metastasis in immortalized mammary gland NMuMG cells.

The homeobox family genes are often dysregulated in various cancer types. Particularly HOXB7 amplification and overexpression correlate with poor prognosis in various cancer such as gastric, pancreatic, and lung cancers. Moreover, HOXB7 is known to contribute to cancer progression by promoting epithelial to mesenchymal transition, anticancer drug resistance, and angiogenesis.

RNA-binding protein LIN28A upregulates transcription factor HIF1α by posttranscriptional regulation via direct binding to UGAU motifs.

Hypoxia-inducible factor 1α (HIF1α) is a transcription factor that regulates angiogenesis under hypoxic conditions. To investigate the posttranscriptional regulatory mechanism of HIF1α, we performed a cell-based screening to reveal potential cis-elements and the regulatory RNA-binding proteins that act as trans-factors. We found that LIN28A promoted HIF1α protein expression independently of the downregulation of microRNA let-7, which is also directly mediated by LIN28A.

Autoantibody Landscape Revealed by Wet Protein Array: Sum of Autoantibody Levels Reflects Disease Status.

Autoantibodies are found in various pathological conditions such as autoimmune diseases, infectious diseases, and malignant tumors. However their clinical implications have not yet been fully elucidated. Herein, we conducted proteome-wide autoantibody screening and quantification with wet protein arrays consisting of proteins synthesized from proteome-wide human cDNA library (HuPEX) maintaining their three-dimensional structure.

Identification of clinical factors related to antibody-mediated immune response to the subfornical organ.

Objective: We recently reported cases of adipsic hypernatremia caused by autoantibodies against the subfornical organ in patients with hypothalamic-pituitary lesions. This study aimed to clarify the clinical features of newly identified patients with adipsic hypernatremia whose sera displayed immunoreactivity to the mouse subfornical organ.

Design: Observational cohort study of patients diagnosed with adipsic hypernatremia in Japan, United States, and Europe.

Curcumin activates G protein-coupled receptor 97 (GPR97) in a manner different from glucocorticoid.

Curcumin is a yellow pigment in turmeric (Curcuma longa) with various physiological effects in the body. To elucidate the molecular mechanisms by which bioactive compounds exert their function, identification of their molecular targets is crucial. In this study, we show that curcumin activates G protein-coupled receptor 97 (GPR97).

Identification of G protein-coupled receptor 55 (GPR55) as a target of curcumin.

The identification of molecular targets of bioactive food components is important to understand the mechanistic aspect of their physiological functions. Here, we have developed a screening system that enables us to determine the activation of G protein-coupled receptors (GPCRs) by food components and have identified GPR55 as a target for curcumin. Curcumin activated GPR55 and induced serum-response element- and serum-response factor-mediated transcription, which were inhibited by Rho kinase and GPR55 antagonists.

Development of an in vitro carcinogenesis model of human papillomavirus-induced cervical adenocarcinoma.

Cervical adenocarcinoma (ADC) is the second most common pathological subtype of cervical cancer after squamous cell carcinoma. It accounts for approximately 20% of cervical cancers, and the incidence has increased in the past few decades, particularly among young patients. The persistent infection of high-risk human papillomavirus (HPV) is responsible for most cervical ADC.

Identification and characterization of the antigen recognized by the germ cell mAb TRA98 using a human comprehensive wet protein array.

TRA98 is a rat monoclonal antibody (mAb) which recognizes a specific antigen in the nuclei of germ cells. mAb TRA98 has been used to understand the mechanism of germ cell development and differentiation in many studies. In mice, the antigen recognized by mAb TRA98 or GCNA1 has been reported to be a GCNA gene product, but despite the demonstration of the immunoreactivity of this mAb in human testis and sperm in 1997, the antigen in humans remains unknown, as of date.

Dermal fibroblast-like cells reprogrammed directly from adipocytes in mouse.

In deep burns, early wound closure is important for healing, and skin grafting is mainly used for wound closure. However, it is difficult to achieve early wound closure in extensive total body surface area deep burns due to the lack of donor sites. Dermal fibroblasts, responsible for dermis formation, may be lost in deep burns.

Sox10 Functions as an Inducer of the Direct Conversion of Keratinocytes Into Neural Crest Cells.

Neural crest cells (NCCs) are highly migratory multipotent cells that play critical roles in embryogenesis. The generation of NCCs is controlled by various transcription factors (TFs) that are regulated by each other and combine to form a regulatory network. We previously reported that the conversion of mouse fibroblasts into NCCs was achieved by the overexpression of only one TF, Sox10; therefore, Sox10 may be a powerful inducer of the conversion of NCCs.

A Pilot Study on the Effect of Anti-Thrombopoietin Antibody on Platelet Count in Patients with Type 2 Diabetes.

Thrombopoietin (THPO) is a circulatory cytokine that plays an important role in platelet production. The presence of anti-THPO antibody relates to thrombocytopenia and is rarely seen in hematopoietic and autoimmune diseases. To date, there had been no reports that focused on the anti-THPO antibody in patients with type 2 diabetes mellitus (T2DM).

Promotion of the Warburg effect is associated with poor benefit from adjuvant chemotherapy in colorectal cancer.

Metabolic reprogramming, including the Warburg effect, is a hallmark of cancer. Indeed, the diversity of cancer metabolism leads to cancer heterogeneity, but accurate assessment of metabolic properties in tumors has not yet been undertaken. Here, we performed absolute quantification of the expression levels of 113 proteins related to carbohydrate metabolism and antioxidant pathways, in stage III colorectal cancer surgical specimens from 70 patients.

Development of INSOL-tag for proteome-wide protein handling and its application in protein array analysis.

Proteomic analysis requires protein tags that enable high-throughput handling; however, versatile tags that can be used in in vitro expression systems are currently lacking. In this study, we developed an insoluble protein tag, INSOL-tag, derived from human transcription factor MafG. The INSOL-tagged target protein is expressed in a eukaryotic in vitro expression system and recovered as a pellet following centrifugation at 19,000 × g for 20 min.

Extracellular transglutaminase 2 induces myotube hypertrophy through G protein-coupled receptor 56.

Skeletal muscle secretes biologically active proteins that contribute to muscle hypertrophy in response to either exercise or dietary intake. The identification of skeletal muscle-secreted proteins that induces hypertrophy can provide critical information regarding skeletal muscle health. Dietary provitamin A, β-carotene, induces hypertrophy of the soleus muscle in mice.

Prognostic significance of IMMT expression in surgically-resected lung adenocarcinoma.

Background: Mitochondrial dysfunction contributes to many types of human disorders and cancer progression. Inner membrane mitochondrial protein (IMMT) plays an important role in the maintenance of mitochondrial structure and function. The aims of this study were to examine IMMT expression in lung adenocarcinoma and evaluate its correlation with clinicopathological parameters and patient prognosis.

UHRF1-KAT7-mediated regulation of TUSC3 expression via histone methylation/acetylation is critical for the proliferation of colon cancer cells.

The epigenetic factor UHRF1 regulates transcription by modulating DNA methylation and histone modification, and plays critical roles in proliferation, development, and tumorigenesis. Here, we show that Wnt/c-Myc signaling upregulates UHRF1, which in turn downregulates TUSC3, a candidate tumor suppressor gene that is frequently deleted or downregulated in several cancers. We also show that UHRF1-mediated downregulation of TUSC3 is required for the proliferation of colon cancer cells.