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. Here, we investigate the genomes, epigenomes, and transcriptomes of MASLD patients to identify signature gene set for more accurate tracking of MASLD progression. @*Methods@#Biopsy-tissue and blood samples from patients with 134 MASLD, comprising 60 steatosis and 74 MASH patients were performed omics analysis. SVM learning algorithm were used to calculate most predictive features. Linear regression was applied to find signature gene set that distinguish the stage of MASLD and to validate their application into independent cohort of MASLD. @*Results@#After performing WGS, WES, WGBS, and total RNA-seq on 134 biopsy samples from confirmed MASLD patients, we provided 1,955 MASLD-associated features, out of 3,176 somatic variant callings, 58 DMRs, and 1,393 DEGs that track MASLD progression. Then, we used a SVM learning algorithm to analyze the data and select the most predictive features. Using linear regression, we identified a signature gene set capable of differentiating the various stages of MASLD and verified it in different independent cohorts of MASLD and a liver cancer cohort. @*Conclusions@#We identified a signature gene set (i.e., CAPG, HYAL3, WIPI1, TREM2, SPP1, and RNASE6) with strong potential as a panel of diagnostic genes of MASLD-associated disease.

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. This system comprises pre-stasis 184D cells, considered normal, and seven cell lines along cancer progression series that are immortalized or additionally acquired anchorage-independent growth. Our analysis of the whole-genome sequencing (WGS) data indicates that those seven cancer progression series cells have somatic mutations whose number ranges from 8,393 to 39,564 (with an average of 30,591) compared to 184D cells. These WGS data and our mutation analysis will provide helpful information to identify driver mutations and elucidate molecular mechanisms for breast carcinogenesis

Inhibition of Chitinase-3-like-1 by K284-6111 Reduces Atopic Skin Inflammation via Repressing Lactoferrin

Chitinase-3-like-1 (CHI3L1) is known to induce inflammation in the progression of allergic diseases. Previous our studies revealed that 2-({3-[2-(1-cyclohexen-1-yl)ethyl]-6,7-dimethoxy-4-oxo-3,4-dihydro-2-quinazolinyl}sulfanyl)-N-(4-ethylphenyl)butanamide (K284-6111; K284), the CHI3L1 inhibiting compound, has the anti-inflammatory effect on neuroinflammation. In this study, we investigated that K284 treatment could inhibit the development of atopic dermatitis (AD). To identify the effect of K284, we used phthalic anhydride (5% PA)-induced AD animal model and in vitro reconstructed human skin model. We analyzed the expression of AD-related cytokine mediators and NF-κB signaling by Western blotting, ELISA and quantitative real-time PCR. Histological analysis showed that K284 treatment suppressed PA-induced epidermal thickening and infiltration of mast cells.K284 treatment also reduced PA-induced release of inflammatory cytokines. In addition, K284 treatment inhibited the expression of NF-κB activity in PA-treated skin tissues and TNF-α and IFN-γ-treated HaCaT cells. Protein-association network analysis indicated that CHI3L1 is associated with lactoferrin (LTF). LTF was elevated in PA-treated skin tissues and TNF-α and IFN-γ-induced HaCaT cells. However, this expression was reduced by K284 treatment. Knockdown of LTF decreased the expression of inflammatory cytokines in TNF-α and IFN-γ-induced HaCaT cells. Moreover, anti-LTF antibody treatment alleviated AD development in PA-induced AD model. Our data demonstrate that CHI3L1 targeting K284 reduces AD-like skin inflammation and K284 could be a promising therapeutic agent for AD by inhibition of LTF expression.

Inhibition of Chitinase-3-like-1 by K284-6111 Reduces Atopic Skin Inflammation via Repressing Lactoferrin

Chitinase-3-like-1 (CHI3L1) is known to induce inflammation in the progression of allergic diseases. Previous our studies revealed that 2-({3-[2-(1-cyclohexen-1-yl)ethyl]-6,7-dimethoxy-4-oxo-3,4-dihydro-2-quinazolinyl}sulfanyl)-N-(4-ethylphenyl)butanamide (K284-6111; K284), the CHI3L1 inhibiting compound, has the anti-inflammatory effect on neuroinflammation. In this study, we investigated that K284 treatment could inhibit the development of atopic dermatitis (AD). To identify the effect of K284, we used phthalic anhydride (5% PA)-induced AD animal model and in vitro reconstructed human skin model. We analyzed the expression of AD-related cytokine mediators and NF-κB signaling by Western blotting, ELISA and quantitative real-time PCR. Histological analysis showed that K284 treatment suppressed PA-induced epidermal thickening and infiltration of mast cells.K284 treatment also reduced PA-induced release of inflammatory cytokines. In addition, K284 treatment inhibited the expression of NF-κB activity in PA-treated skin tissues and TNF-α and IFN-γ-treated HaCaT cells. Protein-association network analysis indicated that CHI3L1 is associated with lactoferrin (LTF). LTF was elevated in PA-treated skin tissues and TNF-α and IFN-γ-induced HaCaT cells. However, this expression was reduced by K284 treatment. Knockdown of LTF decreased the expression of inflammatory cytokines in TNF-α and IFN-γ-induced HaCaT cells. Moreover, anti-LTF antibody treatment alleviated AD development in PA-induced AD model. Our data demonstrate that CHI3L1 targeting K284 reduces AD-like skin inflammation and K284 could be a promising therapeutic agent for AD by inhibition of LTF expression.

Preoperative thrombocytosis predicts prognosis in stage II colorectal cancer patients

PURPOSE: Thrombocytosis is known to be a poor prognostic factor in several types of solid tumors. The prognostic role of preoperative thrombocytosis in colorectal cancer remains limited. The aim of this study is to investigate the prognostic role of preoperative thrombocytosis in stage II colorectal cancer. METHODS: Two hundred eighty-four patients with stage II colorectal cancer who underwent surgical resection between December 2003 and December 2009 were retrospectively reviewed. Thrombocytosis was defined as platelet > 450 × 10(9)/L. We compared patients with thrombocytosis and those without thrombocytosis in terms of survival. RESULTS: The 5-year disease-free survival (DFS) rates were lower in patients with thrombocytosis compared to those without thrombocytosis in stage II colorectal cancer (73.3% vs. 89.6%, P = 0.021). Cox multivariate analysis demonstrated that thrombocytosis (hazard ratio, 2.945; 95% confidence interval, 1.127-7.697; P = 0.028) was independently associated with DFS in patients with stage II colorectal cancer. CONCLUSION: This study showed that thrombocytosis is a prognostic factor predicting DFS in stage II colorectal cancer patients.

A Novel Type of Non-coding RNA, nc886, Implicated in Tumor Sensing and Suppression

nc886 (=vtRNA2-1, pre-miR-886, or CBL3) is a newly identified non-coding RNA (ncRNA) that represses the activity of protein kinase R (PKR). nc886 is transcribed by RNA polymerase III (Pol III) and is intriguingly the first case of a Pol III gene whose expression is silenced by CpG DNA hypermethylation in several types of cancer. PKR is a sensor protein that recognizes evading viruses and induces apoptosis to eliminate infected cells. Like viral infection, nc886 silencing activates PKR and induces apoptosis. Thus, the significance of the nc886:PKR pathway in cancer is to sense and eliminate pre-malignant cells, which is analogous to PKR's role in cellular innate immunity. Beyond this tumor sensing role, nc886 plays a putative tumor suppressor role as supported by experimental evidence. Collectively, nc886 provides a novel example how epigenetic silencing of a ncRNA contributes to tumorigenesis by controlling the activity of its protein ligand.

Small Non-coding Transfer RNA-Derived RNA Fragments (tRFs): Their Biogenesis, Function and Implication in Human Diseases

tRNA-derived RNA fragments (tRFs) are an emerging class of non-coding RNAs (ncRNAs). A growing number of reports have shown that tRFs are not random degradation products but are functional ncRNAs made of specific tRNA cleavage. They play regulatory roles in several biological contexts such as cancer, innate immunity, stress responses, and neurological disorders. In this review, we summarize the biogenesis and functions of tRFs.

Radiologic Analysis of Nasal Septal Fracture in Nasal Bone Fracture Patients through Computerized Tomography / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Diagnosis of nasal bone fracture is important because of not only deformity of the external nose but also because of other additional injuries around the nose. The purpose of this study is to explore the incidence, type, location and direction of nasal septal fracture in nasal bone fracture patients who were diagnosed by nasal bone CT. SUBJECTS AND METHOD: We analysed the medical records and films of 135 nasal bone fracture patients who were diagnosed by computerized tomography from January 2005 to September 2005. The nasal bone fracture was classified by six types on nasal bone CT: unilateral, bilateral, open book, impacted, greenstick, comminuted. The external deviation of nasal bone (20 degree below or up) and correlation between septal fracture and nasal bone fracture were analysed by chi-square test (p<0.05). RESULTS: The incidence of each type of nasal bone fracture is unilateral (41%), bilateral (18%), open book (8%), impacted (6%), green stick (17%), and comminuted (10%). The incidence of combined septal fracture was high in comminuted and impacted rather than in unilateral and bilateral (p<0.05). And there was no correlation between the directions of the trauma force and nasal septal deviation. CONCLUSION: The incidence of concurrent nasal septal fracture when nasal bone fracture occur is relatively high, so we must consider nasal septum more carefully on nasal trauma.

The Effect of Posterior Lumbar Interbody Fusion After Posterolateral Fusion in Degenerative Spondylolisthesis / 대한정형외과학회잡지

PURPOSE: To determine the necessity of an additional posterior lumbar interbody fusion (PLIF) after a posterolateral fusion (PLF) for the treatment of degenerative spondylolisthesis (DS). MATERIALS AND METHODS: A retrospective study, after a minimum follow-up of 2 years was conducted on forty patients who underwent a single level decompression and instrumented fusion for DS with spinal stenosis at the L4-5 level. A PLF was performed in 21 patients, and a circumferential fusion (CF) with an additional PLIF in 19 patients. According to the fusion methods and preoperative segmental mobility, the patients were divided into four groups; s-PLF group (PLF in the stable group, n=13), s-PLIF group (CF in the stable group, n=11), u-PLF group (PLF in the unstable group, n=8), and u-PLIF group (CF in the unstable group, n=8). Clinical and radiographic comparisions between the PLF and PLIF groups were performed. RESULTS: The mean decrements of Oswestry Disability Index (Visual Analog Scale) scores were 29% (5.5), 29% (5.9), 22% (2.6) and 42% (5.9) respectively for the s-PLF, s-PLIF, u-PLF and u-PLIF groups, and a statistical difference was found only between the u-PLF and u-PLIF groups (ODI: p=0.032, VAS: p=0.004). Fusion rates were 92%, 100%, 88% and 100% respectively. The mean slip angle increments were serially 2.5 degrees, -3.1 degrees, -1.5 degrees and -0.3 degrees, and the mean percent slip decrements were 6.7%, 8.7%, 5.1% and 3.7%, and the mean disc height increments were -0.4 mm, 1.8 mm, 0.5 mm and 3.0 mm, and the mean lumbar lordosis increments were 8.6 degrees, 4.7 degrees, -1.9 degrees and 1.9 degrees and the mean sacral tilt increments were 3.8 degrees, 3.4 degrees, -1.3 degrees and 0.9 degrees. Statistical differences were found only between the s-PLF and s-PLIF groups in slip angle increments (p=0.029) and between the s-PLF and s-PLIF groups (p=0.043) and between the u-PLF and u-PLIF groups (p=0.042) in disc height increments. CONCLUSION: PLF alone provided successful clinical outcome in stable group, but CF provided better clinical outcomes in the unstable groups. This study suggests that preoperative segmental mobility may be a criterion to determine whether or not an additional PLIF is necessary in the treatment of lumbar DS.