Chitinase-3-Like Protein 1 as a Therapeutic Target for Inflammatory Diseases.

Chitinase-3-like protein 1 (CHI3L1) is a secreted glycoprotein involved in macrophage polarization, apoptosis, and inflammation, and carcinogenesis. The expression of CHI3L1 is significantly increased in various inflammatory and immunological diseases, such as rheumatoid arthritis, Alzheimer's disease, and atopic dermatitis. Several studies suggest that CHI3L1 may be a viable therapeutic target for these diseases, given its ability to release various pro-inflammatory cytokines, including interleukin (IL)-1β, IL-4, IL-6, IL-13, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ).

Anti-arthritis Effect of Anti-chitinase-3-like 1 Antibody Through Inhibition of MMP3.

Chitinase-3-like 1 (CHI3L1) is a key factor in regulating inflammatory processes and development of rheumatoid arthritis (RA) since is highly produced by synoviocytes and macrophages in the development RA. Collagen-induced arthritis (CIA) model is the most widely used because its pathogenesis is similar to human RA. Thus, we aimed to investigate if anti-CHI3L1 antibody could reduce RA development in the CIA model.

Phosphorylation of an RNA-Binding Protein Rck/Me31b by Hippo Is Essential for Adipose Tissue Aging.

The metazoan lifespan is determined in part by a complex signaling network that regulates energy metabolism and stress responses. Key signaling hubs in this network include insulin/IGF-1, AMPK, mTOR, and sirtuins. The Hippo/Mammalian Ste20-like Kinase1 (MST1) pathway has been reported to maintain lifespan in Caenorhabditis elegans, but its role has not been studied in higher metazoans.

Non-coding RNA RMRP governs RAB31-dependent MMP secretion, enhancing ovarian cancer invasion.

Non-coding RNAs (ncRNAs) are frequently dysregulated in various cancers and have been implicated in the etiology and progression of cancer. Ovarian cancer, the most fatal gynecological cancer, has a poor prognosis and a high patient fatality rate due to metastases. In this study, we classified patients with ovarian cancer into three groups based on their ncRNA expression levels.

Intraosseous xanthoma simultaneously treated with mandibular prognathism using sagittal split ramus osteotomy in the mandible: a case report and literature review.

Xanthomas are benign lesions characterized by the aggregation of lipid-laden histiocytes and foamy cells within tissues. Intraosseous xanthomas (IOXs), especially those in the jaw bone, are rare, with only around 50 cases documented. This case report describes an IOX located at an osteotomy site in the mandible during sagittal split ramus osteotomy (SSRO).

The immune sensitivity caused by DUSP11, an RNA 5'-end maturation phosphatase, is adjusted by a human non-coding RNA, nc886.

All cellular transcripts initially have a tri-phosphate (PPP) group at the 5'-end, recognized as a pathogen-associated molecular pattern (PAMP) by a cell's innate immune system. The removal of 5'-PPP occurs to varying extents, causing immune imbalance. However, how cells manage this situation has not yet been documented.

A1AT dysregulation of metabolically stressed hepatocytes by Kupffer cells drives MASH and fibrosis.

Metabolic dysfunction-associated steatohepatitis (MASH) is associated with the activation of Kupffer cells (KCs) and hepatic stellate cells, at which point a metabolically stressed hepatocyte becomes integral to the progression of the disease. We observed a significant reduction in the level of alpha-1-antitrypsin (A1AT), a hepatocyte-derived secreted factor, in both patients with MASH and mice fed a fast-food diet (FFD). KC-mediated hepatic inflammation, most notably IL-1β, led to the transcriptional inhibition of A1AT by HNF4α.

Multi-Omics Study Reveals Nc886/vtRNA2-1 as a Positive Regulator of Prostate Cancer Cell Immunity.

Noncoding RNA 886 has emerged as a pivotal regulatory RNA with distinct functions across tissues, acting as a regulator of protein activity by directly binding to protein partners. While it is well recognized as a tumor suppressor in prostate cancer, the underlying molecular mechanisms remain elusive. To discover the principal pathways regulated by nc886 in prostate cancer, we used a transcriptomic and proteomic approach analyzing malignant DU145, LNCaP, PC3, and benign RWPE-1 prostate cell line models transiently transfected with in vitro transcribed nc886 or antisense oligonucleotides.

The mystique of epigenetic regulation: the remarkable case of a human noncoding RNA, nc886.

nc886 is a regulatory noncoding RNA that is transcribed by RNA polymerase III (Pol III), is variably expressed in different biological contexts, and plays roles in inflammation and cancer. Epigenetic mechanisms play an intriguing role in regulating nc886 expression. As a maternally imprinted gene and metastable epiallele, nc866 exhibits polymorphic imprinting, with a methylation status that is influenced by environmental and biological factors.

Epigenome-wide analysis across the development span of pediatric acute lymphoblastic leukemia: backtracking to birth.

Background: Cancer is the leading cause of disease-related mortality in children. Causes of leukemia, the most common form, are largely unknown. Growing evidence points to an origin in-utero, when global redistribution of DNA methylation occurs driving tissue differentiation.

The Versatile Roles of nc886, a Fascinating and Peculiar Regulatory Non-Coding RNA, in Cancer.

This review concerns nc886, a 101-nucleotide non-coding RNA (ncRNA). Because nc886 is transcribed by RNA polymerase III (Pol III) and contains a CpG island in its promoter region, its expression is regulated by several transcription factors and the DNA methylation status. These features drive nc886 expression in two opposing directions during tumorigenesis.

TIM-3 on myeloid cells promotes pulmonary inflammation through increased production of galectin-3.

T cell immunoglobulin and mucin-containing molecule 3 (TIM-3) exhibits unique, cell type- and context-dependent characteristics and functions. Here, we report that TIM-3 on myeloid cells plays essential roles in modulating lung inflammation. We found that myeloid cell-specific TIM-3 knock-in (FSF-TIM3/LysM-Cre) mice have lower body weight and shorter lifespan than WT mice.

Galectin-9 Mediates the Functions of Microglia in the Hypoxic Brain Tumor Microenvironment.

Galectin-9 (Gal-9) is a multifaceted regulator of various pathophysiologic processes that exerts positive or negative effects in a context-dependent manner. In this study, we elucidated the distinctive functional properties of Gal-9 on myeloid cells within the brain tumor microenvironment (TME). Gal-9-expressing cells were abundant at the hypoxic tumor edge in the tumor-bearing ipsilateral hemisphere compared with the contralateral hemisphere in an intracranial mouse brain tumor model.

Single-cell RNA sequencing of nc886, a non-coding RNA transcribed by RNA polymerase III, with a primer spike-in strategy.

Single-cell RNA sequencing (scRNA-seq) has emerged as a versatile tool in biology, enabling comprehensive genomic-level characterization of individual cells. Currently, most scRNA-seq methods generate barcoded cDNAs by capturing the polyA tails of mRNAs, which exclude many non-coding RNAs (ncRNAs), especially those transcribed by RNA polymerase III (Pol III). Although previously thought to be expressed constitutively, Pol III-transcribed ncRNAs are expressed variably in healthy and disease states and play important roles therein, necessitating their profiling at the single-cell level.

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.

nc886, an RNA Polymerase III-Transcribed Noncoding RNA Whose Expression Is Dynamic and Regulated by Intriguing Mechanisms.

nc886 is a medium-sized non-coding RNA that is transcribed by RNA polymerase III (Pol III) and plays diverse roles in tumorigenesis, innate immunity, and other cellular processes. Although Pol III-transcribed ncRNAs were previously thought to be expressed constitutively, this concept is evolving, and nc886 is the most notable example. The transcription of nc886 in a cell, as well as in human individuals, is controlled by multiple mechanisms, including its promoter CpG DNA methylation and transcription factor activity.

Generation and analysis of whole-genome sequencing data in human mammary epithelial cells.

Breast cancer is the most common cancer worldwide, and advanced breast cancer with metastases is incurable mainly with currently available therapies. Therefore, it is essential to understand molecular characteristics during the progression of breast carcinogenesis. Here, we report a dataset of whole genomes from the human mammary epithelial cell system derived from a reduction mammoplasty specimen.

Combined Toxicological Effects of Di (2-Ethylhexyl) Phthalate and UV-B Irradiation through Endoplasmic Reticulum Stress-Tight Junction Disruption in Human HaCaT Keratinocytes.

Di (2-ethylhexyl) phthalate (DEHP) is widely used as a plasticizer, and human exposure to DEHP is widespread and frequent. However, information about the combined effect of DEHP and ultraviolet (UV)-B on the skin are still limited. We investigated the cytotoxic effects of DEHP and UV-B on HaCaT keratinocytes and evaluated the related underlying mechanisms involving endoplasmic reticulum (ER) stress signals and the disruption of junction complexes as an effective target for skin inflammation.