Tissue-specific adult stem cells are pivotal in maintaining tissue homeostasis, especially in the rapidly renewing intestinal epithelium. At the heart of this process are leucine-rich repeat-containing G protein-coupled receptor 5-expressing crypt base columnar cells (CBCs) that differentiate into various intestinal epithelial cells. However, while these CBCs are vital for tissue turnover, they are vulnerable to cytotoxic agents. Recent advances indicate that alternative stem cell sources drive the epithelial regeneration post-injury. Techniques like lineage tracing and single-cell RNA sequencing, combined with in vitro organoid systems, highlight the remarkable cellular adaptability of the intestinal epithelium during repair. These regenerative responses are mediated by the reactivation of conserved stem cells, predominantly quiescent stem cells and revival stem cells. With focus on these cells, this review unpacks underlying mechanisms governing intestinal regeneration and explores their potential clinical applications.

Artificial intelligence (AI) in radiology is a rapidly developing field with several prospective clinical studies demonstrating its benefits in clinical practice. In 2022, the Korean Society of Radiology held a forum to discuss the challenges and drawbacks in AI development and implementation. Various barriers hinder the successful application and widespread adoption of AI in radiology, such as limited annotated data, data privacy and security, data heterogeneity, imbalanced data, model interpretability, overfitting, and integration with clinical workflows. In this review, some of the various possible solutions to these challenges are presented and discussed; these include training with longitudinal and multimodal datasets, dense training with multitask learning and multimodal learning, self-supervised contrastive learning, various image modifications and syntheses using generative models, explainable AI, causal learning, federated learning with large data models, and digital twins.

Purpose: The luminal subtype of breast cancer has heterogeneous biological characteristics with respect to the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor-2 (HER2), and Ki-67. We analyzed luminal B breast cancer subcategorized by PR expression and identified clinically relevant prognostic factors. Methods: We collected the clinical and pathologic data of 247 breast cancer patients (stage 1-4) who were diagnosed with luminal B subtype, defined as ER- and/or PR-positive and/or HER2-positive and with a high Ki-67 proliferation index (>14%). We classified them into PR intact and PR low groups according to PR expression pattern. We also analyzed the clinical and pathological data of each group, including age at diagnosis, tumor size, node metastasis, breast and axillary operative method, margin involvement, tumor-node-metastasis (TNM) stage, histological grade, nuclear grade, number of tumors, and expression of ER, PR, Ki-67, and Bcl-2; evaluated recurrence or metastatic characteristics; and analyzed disease-free survival (DFS) and overall survival (OS) in both groups. Results: Among the 247 luminal B breast cancer patients (stage 1-4), 141 were classified into the PR intact group (57.1%) and 106 into the PR low group (42.9%). The PR low group was associated with age >50 years (p=0.001), low Bcl-2 expression (p<0.001), and high proportion of mastectomies (p<0.001). DFS and OS were significantly lower in the PR low group (p=0.025 and 0.024, respectively). Conclusion This study showed that decreased in PR expression (PR low group) in luminal B breast cancer was related to poor prognosis compared to normal PR expression (PR intact group).

Objective: The purpose of this study is to examine the effect of high mobility group AT-hook 1 (HMGA1) on the phenotyptic change of vascular smooth muscle cells (VSMCs). Methods: Gene silencing and overexpression of HMGA1 were introduced to evaluate the effect of HMGA1 expression on the phenotypic change of VSMCs. Marker gene expression of VSMCs was measured by promoter assay, quantitative polymerase chain reaction, and western blot analysis. Common left carotid artery ligation model was used to establish in vivo neointima formation. Results: HMGA1 was expressed strongly in the synthetic type of VSMCs and significantly downregulated during the differentiation of VSMCs. Silencing of HMGA1 in the synthetic type of VSMCs enhanced the expression of contractile marker genes thereby enhanced angiotensin II (Ang II)-dependent contraction, however, significantly suppressed proliferation and migration. Stimulation of contractile VSMCs with platelet-derived growth factor (PDGF) enhanced HMGA1 expression concomitant with the downregulation of marker gene expression which was blocked significantly by the silencing of HMGA1. Silencing of HMGA1 retained the Ang II-dependent contractile function, which was curtailed by PDGF stimulation, however, overexpression of HMGA1 in the contractile type of VSMCs suppressed marker gene expression. Proliferation and migration were enhanced significantly by the overexpression of HMGA1. Furthermore, the Ang II-dependent contraction was reduced significantly by the overexpression of HMGA1. Finally, the expression of HMGA1 was enhanced significantly in the ligated artery, especially in the neointima area. Conclusion HMGA1 plays an essential role in the phenotypic modulation of VSMCs.Therefore, paracrine factors such as PDGF may affect vascular remodeling through the regulation of HMGA1.

The objective of this study is to investigate the clinical and demographic factors that influence the quality of life in patients with Parkinson's disease (PD). This is a crosssectional observational study of 47 patients in 2 hospitals with PD. All participants were asked to complete a disease-specific quality of life (QoL) questionnaire (PDQ-39). We gave a structured questionnaire interview and did a complete neurological examination on the same day. Additionally, we measured depression and dependency with the Geriatric Depression Scale-Short Form (GDS-SF) and the Korean version of the Modified Barthel Index (K-MBI).The PDQ-39 had a significant relationship with each motor part of the Unified Parkinson's Disease Rating Scale, the Korean Mini-Mental State Examination (K-MMSE), the GDS-SF, and the K-MBI (p < 0.05). The factors that independently contributed to the PDQ-39 scores were K-MMSE, GDS-SF, and K-MBI (p < 0.05). Factors having the greatest influence on the PDQ-39 were K-MBI, K-MMSE, and GDS-SF in that order. In addition, the mobility item in the K-MBI was independently a significant relating factor in the PDQ-39 (p < 0.05). These results demonstrated that dependency, especially with the mobility issue, was the greatest influence on the QoL in patients with PD.

Emerging evidences have reported that periodontitis can be a risk factor for the pathogenesis of various systemic diseases. Porphyromonas gingivalis (Pg), one of the crucial pathogens in chronic periodontitis, has been spotlighted as a potential cause for the promotion and acceleration of periodontitis-associated systemic disorders. To investigate the association between Pg and intestinal disease or homeostasis, we treated Pg-derived lipopolysaccharide (LPS) in murine colitis model or intestinal organoid, respectively. Pg-derived LPS (Pg LPS) was administrated into chemically induced murine colitis model and disease symptoms were monitored compared with the infusion of LPS derived from E. coli (Ec LPS). Organoids isolated and cultured from mouse small intestine were treated with Pg or Ec LPS and further analyzed for the generation and composition of organoids. In vivo observations demonstrated that both Pg and Ec LPS exerted slight protective effects against murine colitis. Pg LPS did not affect the generation and growth of intestinal epithelial organoids. Among subtypes of epithelial cells, markers for stem cells, goblet cells or Paneth cells were changed in response to Pg LPS. Taken together, these results indicate that Pg LPS leads to partial improvement in colitis and that its treatment does not significantly affect the self-organization of intestinal organoids but may regulate the epithelial composition.
Acceleration ; Animals ; Chronic Periodontitis ; Colitis ; Epithelial Cells ; Goblet Cells ; Homeostasis ; Intestinal Diseases ; Intestinal Mucosa ; Intestine, Small ; Mice ; Organoids ; Paneth Cells ; Periodontitis ; Porphyromonas gingivalis ; Porphyromonas ; Risk Factors ; Stem Cells

Olfactory impairment is the most common clinical manifestation among the elderly, and its prevalence increases sharply with age. Notably, growing evidence has shown that olfactory dysfunction is the first sign of neurodegeneration, indicating the importance of olfactory assessment as an early marker in the diagnosis of neurological disorders. In this review, we describe the nature of olfactory dysfunction and the advantage of using animal models in olfaction study, and we include a brief introduction to olfactory behavior tests widely used in this field. The contribution of microglia in the neurodegenerative processes including olfactory impairment is then discussed to provide a comprehensive description of the physiopathological role of interactions between neurons and microglia within the olfactory system.
Aged ; Behavior Rating Scale ; Diagnosis ; Humans ; Microglia ; Models, Animal ; Nervous System Diseases ; Neurodegenerative Diseases ; Neurons ; Prevalence ; Smell

Retinal pigment epithelium (RPE) is a major component of the eye. This highly specialized cell type facilitates maintenance of the visual system. Because RPE loss induces an irreversible visual impairment, RPE generation techniques have recently been investigated as a potential therapeutic approach to RPE degeneration. The microRNA-based technique is a new strategy for producing RPE cells from adult stem cell sources. Previously, we identified that antisense microRNA-410 (anti-miR-410) induces RPE differentiation from amniotic epithelial stem cells. In this study, we investigated RPE differentiation from umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) via anti-miR-410 treatment. We identified miR-410 as a RPE-relevant microRNA in UCB-MSCs from among 21 putative human RPE-depleted microRNAs. Inhibition of miR-410 induces overexpression of immature and mature RPE-specific factors, including MITF, LRAT, RPE65, Bestrophin, and EMMPRIN. The RPE-induced cells were able to phagocytize microbeads. Results of our microRNA-based strategy demonstrated proof-of-principle for RPE differentiation in UCB-MSCs by using anti-miR-410 treatment without the use of additional factors or exogenous transduction.
Adult Stem Cells ; Antigens, CD147 ; Humans ; Mesenchymal Stromal Cells* ; MicroRNAs ; Microspheres ; Retinal Pigment Epithelium* ; Retinaldehyde* ; Stem Cells ; Umbilical Cord* ; Vision Disorders

Recent advances have shown the direct reprogramming of mouse and human fibroblasts into induced neural stem cells (iNSCs) without passing through an intermediate pluripotent state. Thus, direct reprogramming strategy possibly provides a safe and homogeneous cellular platform. However, the applications of iNSCs for regenerative medicine are limited by the restricted availability of cell sources. Human umbilical cord blood (hUCB) cells hold great potential in that immunotyped hUCB units can be immediately obtained from public banks. Moreover, hUCB samples do not require invasive procedures during collection or an extensive culture period prior to reprogramming. We recently reported that somatic cells can be directly converted into iNSCs with high efficiency and a short turnaround time. Here, we describe the detailed method for the generation of iNSCs derived from hUCB (hUCB iNSCs) using the lineage-specific transcription factors SOX2 and HMGA2. The protocol for deriving iNSC-like colonies takes 1~2 weeks and establishment of homogenous hUCB iNSCs takes additional 2 weeks. Established hUCB iNSCs are clonally expandable and multipotent producing neurons and glia. Our study provides an accessible method for generating hUCB iNSCs, contributing development of in vitro neuropathological model systems.
Animals ; Fetal Blood* ; Fibroblasts ; Humans* ; In Vitro Techniques ; Methods ; Mice ; Neural Stem Cells* ; Neuroglia ; Neurons ; Regenerative Medicine ; Transcription Factors ; Umbilical Cord*

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by selective death of motor neurons in the central nervous system. The main cause of the disease remains elusive, but several mutations have been associated with the disease process. In particular, mutant superoxide dismutase 1 (SOD1) protein causes oxidative stress by activating glia cells and contributes to motor neuron degeneration. KCHO-1, a novel herbal combination compound, contains 30% ethanol and the extracts of nine herbs that have been commonly used in traditional medicine to prevent fatigue or inflammation. In this study, we investigated whether KCHO-1 administration could reduce oxidative stress in an ALS model. KCHO-1 administered to ALS model mice improved motor function and delayed disease onset. Furthermore, KCHO-1 administration reduced oxidative stress through gp91(phox) and the MAPK pathway in both classically activated microglia and the spinal cord of hSOD1(G93A) transgenic mice. The results suggest that KCHO-1 can function as an effective therapeutic agent for ALS by reducing oxidative stress.
Amyotrophic Lateral Sclerosis* ; Animals* ; Central Nervous System ; Ethanol ; Fatigue ; Inflammation ; Medicine, Traditional ; Mice ; Mice, Transgenic ; Microglia ; Models, Animal* ; Motor Neurons ; Neurodegenerative Diseases ; Neuroglia ; Oxidative Stress* ; Spinal Cord ; Superoxide Dismutase