CRISPR/Cas9-Mediated Knockout Zebrafish: Unraveling the Pathogenesis of Erythropoietic Protoporphyria and Facilitating Drug Screening.

Erythropoietic protoporphyria (EPP1) results in painful photosensitivity and severe liver damage in humans due to the accumulation of fluorescent protoporphyrin IX (PPIX). While zebrafish () models for porphyria exist, the utility of ferrochelatase () knockout zebrafish, which exhibit EPP, for therapeutic screening and biological studies remains unexplored. This study investigated the use of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated -knockout zebrafish larvae as a model of EPP1 for drug screening.

Mitochondrial Fission Is Involved in Heat Resistance in Zebrafish.

Global warming and extreme weather events pose a significant threat to global biodiversity, with rising water temperatures exerting a profound influence on fish conservation and fishery development. In this study, we used zebrafish as a model organism to explore the impact of a heat acclimation period on their survival rates. The results demonstrated that a 2-month heat acclimation period almost completely mitigated heat stress-induced mortality in zebrafish.

Prediction of Lymph Node Metastasis in T1 Colorectal Cancer Using Artificial Intelligence with Hematoxylin and Eosin-Stained Whole-Slide-Images of Endoscopic and Surgical Resection Specimens.

According to the current guidelines, additional surgery is performed for endoscopically resected specimens of early colorectal cancer (CRC) with a high risk of lymph node metastasis (LNM). However, the rate of LNM is 2.1-25.

Revealing the pathogenesis of keloids based on the status: Active vs inactive.

Recently, the pathomechanisms of keloids have been extensively researched using transcriptomic analysis, but most studies did not consider the activity of keloids. We aimed to profile the transcriptomics of keloids according to their clinical activity and location within the keloid lesion, compared with normal and mature scars. Tissue samples were collected (keloid based on its activity (active and inactive), mature scar from keloid patients and normal scar (NS) from non-keloid patients).

Revisiting roles of mast cells and neural cells in keloid: exploring their connection to disease activity.

Background: Mast cells (MCs) and neural cells (NCs) are important in a keloid microenvironment. They might contribute to fibrosis and pain sensation within the keloid. However, their involvement in pathological excessive scarring has not been adequately explored.

Non-contrast low-dose CT can be used for volumetry of ADPKD.

Background: Kidney volume provides important information for the diagnosis and prognosis of autosomal dominant polycystic kidney disease (ADPKD), as well as for the evaluation of the effects of drugs such as tolvaptan. Non-contrast computed tomography (CT) is commonly used for volumetry, and this study examined the correspondence and correlation of kidney volume measured by standard-dose or low-dose CT.

Methods: Axial standard-dose and low-dose CT images with 1-mm slices were obtained from 24 ADPKD patients.

Intercellular cross-talk through lineage-specific gap junction of cancer-associated fibroblasts related to stromal fibrosis and prognosis.

Stromal fibrosis in cancer is usually associated with poor prognosis and chemotherapy resistance. It is thought to be caused by fibroblasts; however, the exact mechanism is not yet well understood. The study aimed to identify lineage-specific cancer-associated fibroblast (CAF) subgroup and their associations with extracellular matrix remodeling and clinical significances in various tumor types using single-cell and bulk RNA sequencing data.

Narirutin ameliorates alcohol-induced liver injury by targeting MAPK14 in zebrafish larvae.

Background: Alcohol-associated liver disease (ALD) encompasses a range of hepatic abnormalities, including isolated alcoholic steatosis, steatohepatitis, and cirrhosis. The flavanone-7-O-glycoside narirutin (NRT), the primary flavonoid in citrus peel, has antioxidant, anti-inflammatory, and lipid-lowering activity. We investigated the effects of NRT on liver injury induced by alcohol and explored the underlying mechanisms.

The Prognostic Value of Micropapillary Pattern in Colon Cancer and Its Role as a High-Risk Feature in Patients With Stage II Disease.

Background: The association of a micropapillary pattern with oncologic outcomes has not been fully studied in patients with colon cancer.

Objective: We evaluated the prognostic value of a micropapillary pattern, especially for patients with stage II colon cancer.

Design: A retrospective comparative cohort study using propensity score matching.

Loss of pex5 sensitizes zebrafish to fasting due to deregulated mitochondria, mTOR, and autophagy.

Animal models have been utilized to understand the pathogenesis of Zellweger spectrum disorders (ZSDs); however, the link between clinical manifestations and molecular pathways has not yet been clearly established. We generated peroxin 5 homozygous mutant zebrafish (pex5) to gain insight into the molecular pathogenesis of peroxisome dysfunction. pex5 display hallmarks of ZSD in humans and die within one month after birth.

Impact of needle type on substitution volume during online hemodiafiltration: plastic cannulae versus metal needles.

Background: Plastic cannulae have attracted increasing interest as an alternative to traditional metal needles with the aim of reducing cannulation-related complications. We investigated whether the substitution volumes during hemodiafiltration differ using these two types of needles in dialysis patients.

Methods: An intervention study involving 26 hemodialysis patients was conducted in Korea between March and September in 2021.

Utility of artificial intelligence with deep learning of hematoxylin and eosin-stained whole slide images to predict lymph node metastasis in T1 colorectal cancer using endoscopically resected specimens; prediction of lymph node metastasis in T1 colorectal cancer.

Background: When endoscopically resected specimens of early colorectal cancer (CRC) show high-risk features, surgery should be performed based on current guidelines because of the high-risk of lymph node metastasis (LNM). The aim of this study was to determine the utility of an artificial intelligence (AI) with deep learning (DL) of hematoxylin and eosin (H&E)-stained endoscopic resection specimens without manual-pixel-level annotation for predicting LNM in T1 CRC. In addition, we assessed AI performance for patients with only submucosal (SM) invasion depth of 1000 to 2000 μm known to be difficult to predict LNM in clinical practice.

Fusions in 1113 Solid Tumors in a Single Institution.

Most fusions occur at very low frequencies in various common cancers. Recent recommendations on testing recommend immunohistochemistry (IHC) as the initial test for tumor types with a low frequency of fusions. This study investigated the accuracy of an IHC assay to detect fusions and characterize the clinicopathological and molecular features of -rearranged tumors.

PRRX1 is a master transcription factor of stromal fibroblasts for myofibroblastic lineage progression.

Although stromal fibroblasts play a critical role in cancer progression, their identities remain unclear as they exhibit high heterogeneity and plasticity. Here, a master transcription factor (mTF) constructing core-regulatory circuitry, PRRX1, which determines the fibroblast lineage with a myofibroblastic phenotype, is identified for the fibroblast subgroup. PRRX1 orchestrates the functional drift of fibroblasts into myofibroblastic phenotype via TGF-β signaling by remodeling a super-enhancer landscape.

Expression of SLC22A18 regulates oxaliplatin resistance by modulating the ERK pathway in colorectal cancer.

Although oxaliplatin-based chemotherapy is the current standard adjuvant therapy for colorectal cancer (CRC), the molecular mechanisms underlying oxaliplatin resistance remain unclear. Here, we examined the molecular mechanisms underlying SLC22A18-associated oxaliplatin resistance and strategies for overcoming oxaliplatin resistance. We evaluated the association between SLC22A18 and prognosis in 337 patients with CRC and its functional significance and studied the mechanisms through which SLC22A18 affects oxaliplatin resistance development in CRC cells, using CRC cell lines and patient-derived cells (PDCs).

Histologic Activity and Steroid Use History Are Risk Factors of Clinical Relapse in Ulcerative Colitis With Mayo Endoscopic Subscore of 0 or 1.

Background: The treatment goal of ulcerative colitis (UC) has changed from the control of symptoms to mucosal healing, previously evaluated mainly by endoscopy. Recently, the importance of histologic activity has emerged. Therefore, this study aimed to investigate the risk of clinical relapse according to histologic activity in UC with a Mayo endoscopic subsccore (MES) of 0 or 1.

Is High-Grade Tumor Budding an Independent Prognostic Factor in Stage II Colon Cancer?

Background: Risk factors, including lymphatic, vascular, and perineural invasion, are considered indications for adjuvant treatment in stage II colon cancer. However, tumor budding is not included in the above risk factors.

Objective: This study aimed to assess the value of tumor budding as a prognostic factor in stage II colon cancer.

Consistency of the estimated target weights and ECW/TBW using BIA after hemodialysis in patients between standing and lying-down positions.

Background: As hemodialysis is administered with the patient lying down, the distribution of body fluid is stable in the lying position, which is why this position is recommended for bioimpedance analysis (BIA). Although the InBody S10 is widely used for hemodialysis patients in the lying position, clinicians must make the measurements in person. In contrast, patients can use the InBody 770 to obtain measurements by themselves in the standing position, which may be more convenient.

High cortisol levels are associated with oxidative stress and mortality in maintenance hemodialysis patients.

Background: Chronic stimulation of the mineralocorticoid receptor has been suggested as one of the potential causes of cardiovascular events and death in patients with end-stage renal disease. This observational cohort study was performed to demonstrate that serum cortisol might be a predictive marker for patient mortality and to evaluate its association with oxidized low-density lipoprotein (oxLDL) in hemodialysis (HD) patients.

Methods: Patients receiving HD three times a week were screened for enrollment at two institutions.

Integrated Analysis of Single-Cell and Spatial Transcriptomics in Keloids: Highlights on Fibrovascular Interactions in Keloid Pathogenesis.

Studies on the etiopathogenesis of keloids mostly have focused on fibroblasts and their dysfunction. In this study, two cutting-edge technologies, single-cell RNA sequencing and spatial transcriptomics, were applied to uncover the underlying pathophysiology of keloids. Keloid tissue samples and normal skin control data were analyzed as well as those of patient-matched keloid and normal mature scar.

Revised Nodal Staging Integrating Tumor Deposit Counts With Positive Lymph Nodes in Patients With Stage III Colon Cancer.

Objective: We evaluated the prognostic value of tumor deposit (TD) counts and incorporated them with the number of positive lymph nodes to develop a revised nodal staging.

Summary Background Data: The current American Joint Committee on Cancer (AJCC) staging on colon cancer includes the TDs only for nodenegative patients, as N1c, and their counts are not considered.

Methods: We included consecutive patients with stage III colorectal cancer who underwent curative resections between January 2010 and December 2019.

Quality of life in patients with diabetic nephropathy: findings from the KNOW-CKD (Korean Cohort Study for Outcomes in Patients with Chronic Kidney Disease) cohort.

Background: Diabetic nephropathy (DN) can affect quality of life (QoL) because it requires arduous lifelong management. This study analyzed QoL differences between DN patients and patients with other chronic kidney diseases (CKDs).

Methods: The analysis included subjects (n = 1,766) from the KNOW-CKD (Korean Cohort Study for Outcomes in Patients with Chronic Kidney Disease) cohort who completed the Kidney Disease Quality of Life Short Form questionnaire.

Transgenic fluorescent zebrafish lines that have revolutionized biomedical research.

Since its debut in the biomedical research fields in 1981, zebrafish have been used as a vertebrate model organism in more than 40,000 biomedical research studies. Especially useful are zebrafish lines expressing fluorescent proteins in a molecule, intracellular organelle, cell or tissue specific manner because they allow the visualization and tracking of molecules, intracellular organelles, cells or tissues of interest in real time and in vivo. In this review, we summarize representative transgenic fluorescent zebrafish lines that have revolutionized biomedical research on signal transduction, the craniofacial skeletal system, the hematopoietic system, the nervous system, the urogenital system, the digestive system and intracellular organelles.

Validation of ZMYND8 as a new treatment target in hepatocellular carcinoma.

Background: ZMYND8 (Zinc finger MYND (Myeloid, Nervy and DEAF-1)-type containing 8) has been known to play an important role in tumor regulation in various types of cancer. However, the results of ZMYND8 expression and their clinical significance in hepatocellular carcinoma (HCC) have not yet been published. In the present study, we investigate the expression of ZMYND8 protein and mRNA in HCC and elucidate its prognostic significance.