Primary cilia function as critical sensory organelles that mediate multiple signaling pathways, including the Hedgehog (Hh) pathway, which is essential for organ patterning and morphogenesis. Disruptions in Hh signaling have been implicated in supernumerary tooth formation and molar fusion in mutant mice. Cilk1, a highly conserved serine/threonine-protein kinase localized within primary cilia, plays a critical role in ciliary transport. Loss of Cilk1 results in severe ciliopathy phenotypes, including polydactyly, edema, and cleft palate. However, the role of Cilk1 in tooth development remains unexplored. In this study, we investigated the role of Cilk1 in tooth development. Cilk1 was found to be expressed in both the epithelial and mesenchymal compartments of developing molars. Cilk1 deficiency resulted in altered ciliary dynamics, characterized by reduced frequency and increased length, accompanied by downregulation of Hh target genes, such as Ptch1 and Sostdc1, leading to the formation of diastemal supernumerary teeth. Furthermore, in Cilk1^-/-;PCS1-MRCS1^△/△ mice, which exhibit a compounded suppression of Hh signaling, we uncovered a novel phenomenon: diastemal supernumerary teeth can be larger than first molars. Based on these findings, we propose a progressive model linking Hh signaling levels to sequential changes in tooth patterning: initially inducing diastemal supernumerary teeth, then enlarging them, and ultimately leading to molar fusion. This study reveals a previously unrecognized role of Cilk1 in controlling tooth morphology via Hh signaling and highlights how Hh signaling levels shape tooth patterning in a gradient-dependent manner.
Animals ; Hedgehog Proteins/physiology* ; Mice ; Signal Transduction/physiology* ; Tooth, Supernumerary ; Molar ; Cilia/physiology* ; Odontogenesis/physiology* ; Patched-1 Receptor ; Protein Serine-Threonine Kinases/physiology* ; Mice, Knockout ; Adaptor Proteins, Signal Transducing

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.

Objective: To evaluate the safety and clinical outcomes of the Passeo-18 Lux drug-coated balloon (DCB) in endovascular revascularization procedures under real-world conditions in a Korean population with atherosclerotic disease of the infrainguinal arteries, including below-the-knee (BTK) arteries. Materials and Methods: Eight institutions in the Republic of Korea participated in this prospective, multicenter, single-arm, post-market surveillance study. Two hundred patients with Rutherford class 2–5 peripheral arterial disease and infrainguinal lesions suitable for endovascular treatment were competitively enrolled. Data were collected at baseline, the time of intervention, discharge, and 1-, 6-, 12-, and 24-month follow-up visits. The primary safety endpoint was freedom from major adverse events (MAE) within 6 months (except when limiting the time frame for procedure- or device-related mortality to within 30 days), and the primary effectiveness endpoint was freedom from clinically driven target lesion revascularization (CDTLR) within 12 months after the procedure. Results: A total of 197 patients with 332 target lesions were analyzed. Two-thirds of the patients had diabetes mellitus, and 41.6% had chronic limb-threatening ischemia. The median target lesion length was 100 mm (interquartile range: 56–133 mm).Of the target lesions, 35.2% were occlusions, and 14.8% were located in the BTK arteries. Rate of freedom from MAE was 97.9% at 6 months, and the rate of freedom from CD-TLR was 95.0% and 92.2% at 12 and 24 months, respectively. Subgroup analysis of 43 patients and 49 target lesions involving the BTK arteries showed rate of freedom from MAE of 92.8% at 6 months and rates of freedom from CD-TLR of 88.8% and 84.4% at 12 and 24 months, respectively. Conclusion The results of the present study, including the BTK subgroup analysis, showed outcomes comparable to those of other DCB studies, confirming the safety and effectiveness of Passeo-18 Lux DCB in the Korean population.

Spinal trauma accounts for a large portion of injuries to the spine area, particularly as societies are entering an era of aging populations. Consequently, spine fractures accompanied by osteoporosis are becoming more prevalent. Achieving successful fusion surgery in patients with spine fractures associated with osteoporosis is even more challenging. Pseudarthrosis in the spine does not yield clinically favorable results; however, considerable effort has been made to achieve successful fusion, and the advancement of bone graft substitutes has been particularly crucial in this regard. Autograft bone is considered the best fusion material but is limited in use due to the quantity that can be harvested during surgery and associated complications. Accordingly, various bone graft substitutes are currently being used, although no specific guidelines are available and this mainly depends on the surgeon's choice. Therefore, the purpose of this review, across part I/II, is to summarize bone graft substitutes commonly used in spine surgery for spine fusion in patients with spine trauma and to update the latest knowledge on the role of recombinant human bone morphogenetic protein-2.

Objectives: . Thyroid cancer is the most common endocrine tumor, with rapidly increasing incidence worldwide. However, its transcriptomic characteristics associated with immunological signatures, driver fusions, and recurrence markers remain unclear. We aimed to investigate the transcriptomic characteristics of advanced papillary thyroid cancer. Methods: . This study included 282 papillary thyroid cancer tumor samples and 155 normal samples from Chungnam National University Hospital and Seoul National University Hospital. Transcriptomic quantification was determined by high-throughput RNA sequencing. We investigated the associations of clinical parameters and molecular signatures using RNA sequencing. We validated predictive biomarkers using the Cancer Genome Atlas database. Results: . Through a comparison of differentially expressed genes, gene sets, and pathways in papillary thyroid cancer compared to normal tumor-adjacent tissue, we found increased immune signaling associated with cytokines or T cells and decreased thyroid hormone synthetic pathways. In addition, patients with recurrence presented increased CD8+ T-cell and Th1-cell signatures. Interestingly, we found differentially overexpressed genes related to immune-escape signaling such as CTLA4, IDO1, LAG3, and PDCD1 in advanced papillary thyroid cancer with a low thyroid differentiation score. Fusion analysis showed that the PI3K and mitogen-activated protein kinase (MAPK) signaling pathways were regulated differently according to the RET fusion partner genes (CCDC6 or NCOA4). Finally, we identified HOXD9 as a novel molecular biomarker that predicts the recurrence of thyroid cancer in addition to known risk factors (tumor size, lymph node metastasis, and extrathyroidal extension). Conclusion . We identified a high association with immune-escape signaling in the immune-hot group with aggressive clinical characteristics among Korean thyroid cancer patients. Moreover, RET fusion differentially regulated PI3K and MAPK signaling depending on the partner gene of RET, and HOXD9 was found to be a recurrence marker for advanced papillary thyroid cancer.

BACKGROUND: Although Eriobotrya japonica leaves have been studied as a raw material for various cosmetic products, little is known about the anti-oxidant, anti-inflammatory, and anti-melanogenic activities of Eriobotrya japonica leaf ethanol extract (EJEE). METHODS: This study was conducted to evaluate the anti-oxidant, anti-inflammatory, and anti-melanogenic activities of EJEE using different in vitro models. In addition, we investigated the potential irritation of EJEE to skin and eye using animal alternative tests. RESULTS: The total content of polyphenols, one of the active constituents of EJEE, was analyzed by high-performance liquid chromatography and found to contain 88.68 mg tannic acid equivalent/g. EJEE showed a concentration-dependent 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity, 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) radical scavenging activity, and a superoxide dismutase-like activity. The anti-inflammatory effect of 0.5% (w/v) EJEE was demonstrated by a reduction in lipopolysaccharide-induced nitric oxide and tumor necrosis factor-alpha levels in RAW 264.7 cells. EJEE also significantly inhibited melanogenesis in melanocyte stimulating hormone-induced B16F1 cells. EJEE did not show any irritation in skin and eye in animal alternative test. CONCLUSIONS: These results indicate that the EJEE possesses anti-oxidant, anti-inflammatory, and anti-melanogenic activities, while it did not induce toxicity or irritation in neither skin nor eye. Therefore, EJEE can be used as a cosmetic ingredient for skin improvement.
Animals ; Chromatography, Liquid ; Eriobotrya ; Ethanol ; In Vitro Techniques ; Melanocytes ; Nitric Oxide ; Polyphenols ; RAW 264.7 Cells ; Skin ; Superoxides ; Tannins ; Tumor Necrosis Factor-alpha

BACKGROUND: Superficial dermatomycoses are fungal infections of the skin, hair, or nails and are most commonly caused by dermatophytes. Superficial dermatomycoses are very common diseases in the field of dermatology; however, their prevalence and clinical characteristics vary with geographical areas and populations. Moreover, pathogenic species change constantly over time. OBJECTIVE: This multicenter study aimed to investigate the epidemiologic and clinical findings of tinea corporis, tinea faciale, and tinea capitis in Korea during 2016-2017. In addition, we sought to identify the pathogenic organism causing these three different types of fungal infections. METHODS: Total 453 patients from the dermatology clinics of 13 tertiary hospitals in Korea were enrolled in this study. Information regarding demographic characteristics, comorbidities, occupation, family history of superficial dermatomycoses, suspected routes of infection, and treatment was collected. Fungal cultures and molecular analyses were performed for patients with tinea corporis, tinea faciale, and tinea capitis. RESULTS: Of the 453 patients, 275 were men and 178 were women. With respect to past history, 214 patients (53.4%) had at least one comorbidity. Tinea corporis (27.3%) was the most common form of superficial dermatomycosis, followed by tinea pedis (23.2%) and tinea unguium (16.6%). Overall, the fungal culture positivity was 77.8% (126/162). Trichophyton rubrum was the most common causative organism for tinea corporis (66.7%, 68/80) and tinea faciale (43.8%, 14/23), while Microsporum canis was the most common causative organism for tinea capitis (36.7%, 11/23). CONCLUSION Trichophyton rubrum was consistently the most common causative organism of superficial dermatomycoses, except for tinea capitis in Korea.

BACKGROUND: There have been several therapeutic guidelines for onychomycosis in different countries and advances in its diagnosis and treatment. Optimal treatment decision-making is affected by healthcare systems and cultural backgrounds of countries. OBJECTIVE: The executive committee for onychomycosis guideline of the Korean Society for Medical Mycology aims to provide up-to-date practical guidelines for onychomycosis management in Koreans. METHODS: The committee thoroughly reviewed relevant literature and previous guidelines. The structured algorithmic guideline was developed by experts' consensus. RESULTS: The optimal treatments can be selected alone or in combination based on the nail and patient variables. Three major classes of treatment are available: standard (topical or oral antifungals), additional (nail removal), and alternative treatments (laser). Both topical and oral antifungals alone are appropriate for mild onychomycosis, while oral antifungals are primarily recommended for moderate-to-severe cases if not contraindicated. Combined topical and oral antifungals are recommended to increase the efficacy in moderate-to-severe cases. Additional infected nail removal is also considered for moderate-to-severe onychomycosis, which is unresponsive to standard medical treatment alone. Laser therapy can be an alternative without significant side effects when standard medical treatments cannot be applied regardless of onychomycosis severity. After treatment course completion, periodic therapeutic response monitoring and onychomycosis preventive measures should be rendered to reduce recurrence. CONCLUSION The Korean consensus guideline provides evidence-based recommendations to promote good outcomes of onychomycosis. The proposed algorithm is simple and easy to comprehend, allowing clinicians to facilitate optimal treatment decision-making for onychomycosis in clinical practice.

BACKGROUND: The prevalence of onychomycosis is increasing due to the recent increase of the elderly population and immunosuppressed individuals. Clinical studies on onychomycosis have been reported several times in Korea. However, the public awareness of onychomycosis has not received considerable attention, and there have been no Korean studies focused on it. OBJECTIVE: To evaluate public awareness and experience of onychomycosis in Korean. METHODS: A total of 621 participants were given questions developed for this survey. Sociodemographic characteristics, public awareness, general knowledge and experience about onychomycosis, and diagnostic and treatment behavior were surveyed. RESULTS: According to this survey, 99.5% of respondents have heard of onychomycosis, 79.4% of respondents experienced onychomycosis suspicious symptoms, and 52.8% of them responded that onychomycosis can be completely cured only by cleansing the hands and feet. The rate of self-diagnosis was 64.1% among the respondents who experienced symptoms. Only 23.9% of the respondents who were diagnosed with onychomycosis visited the hospital for the first time. Of the respondents, 54.6% who were treated at the hospital discontinued their treatments before complete cure mainly because of long treatment period. CONCLUSION Participants were well aware of onychomycosis, but the rate of self-diagnosis was high. They generally agreed to the importance of hospital treatment, but the number of patients visiting hospital was low. Moreover, people frequently discontinue their hospital treatment despite insufficient treatment duration. Patient's behaviors need to be changed, and the roles of dermatologists are important in the diagnosis, treatment, and education of the patients.

Despite advancements in treating ruptured cerebral aneurysms, an aneurysmal subarachnoid hemorrhage (aSAH) is still a grave cerebrovascular disease associated with a high rate of morbidity and mortality. Based on the literature published to date, worldwide academic and governmental committees have developed clinical practice guidelines (CPGs) to propose standards for disease management in order to achieve the best treatment outcomes for aSAHs. In 2013, the Korean Society of Cerebrovascular Surgeons issued a Korean version of the CPGs for aSAHs. The group researched all articles and major foreign CPGs published in English until December 2015 using several search engines. Based on these articles, levels of evidence and grades of recommendations were determined by our society as well as by other related Quality Control Committees from neurointervention, neurology and rehabilitation medicine. The Korean version of the CPGs for aSAHs includes risk factors, diagnosis, initial management, medical and surgical management to prevent rebleeding, management of delayed cerebral ischemia and vasospasm, treatment of hydrocephalus, treatment of medical complications and early rehabilitation. The CPGs are not the absolute standard but are the present reference as the evidence is still incomplete, each environment of clinical practice is different, and there is a high probability of variation in the current recommendations. The CPGs will be useful in the fields of clinical practice and research.
Aneurysm ; Brain Ischemia ; Cerebrovascular Disorders ; Diagnosis ; Disease Management ; Hydrocephalus ; Intracranial Aneurysm ; Mortality ; Neurology ; Quality Control ; Rehabilitation ; Risk Factors ; Search Engine ; Subarachnoid Hemorrhage ; Surgeons