Comprehensive transcriptome profiling between balding and non-balding scalp of female pattern hair loss in Asian.

While many gene expression studies have focused on male pattern baldness (MPB), few studies have investigated the genetic differences between bald and non-bald hair follicles in female pattern hair loss (FPHL). This study aimed to identify molecular biomarkers associated with FPHL through genetic analysis of paired bald and non-bald hair follicles from 18 FPHL patients, using next-generation sequencing (NGS) techniques. RNA transcriptome analysis was performed to identify differentially expressed genes (DEGs) between bald and non-bald hair follicles in FPHL. The DEGs were validated using real-time PCR, and protein expression was confirmed through immunohistochemistry and western blot analysis. Our findings suggest that HOXB13, SFRP2, PTGDS, CXCR3, SFRP4, SOD3, and DCN are significantly upregulated in bald hair follicles compared to non-bald hair follicles in FPHL. SFRP2 and PTGDS were found to be consistently highly expressed in bald hair follicles in all 18 samples. Additionally, elevated protein levels of SFRP2 and PTGDS were confirmed through western blot and immunohistochemical analysis. Our study identified SFRP2 and PTGDS as potential biomarkers for FPHL and suggests that they may play a role in inducing hair loss in this condition. These findings provide a foundation for further research on the pathogenesis of FPHL and potential therapeutic targets.

The Effect of Telehealth on Patterns of Health Care Utilization and Medication Prescription in Patients with Diabetes or Hypertension During COVID-19: A Nationwide Study.

Background: In response to the coronavirus disease-19 pandemic, audio-based telehealth services for consultation and medication prescription were temporarily introduced in Korea. This study investigated the impact of telehealth services on patterns of health care utilization and medication prescription in patients with hypertension or diabetes. Methods: The 2019 to 2021 Health Insurance Review and Assessment Service claims data were used. The difference-in-difference approach was used to investigate the effect of telehealth services between the case and control group before and after the intervention period. The pre-intervention period was from February 24, 2019, to February 23, 2020, and the post-intervention period from February 24, 2020, to February 23, 2021. The control group included individuals who used in-person outpatient services and the case group those who utilized both telehealth and in-person services. Results: A total of 250,640 patients with hypertension and 154,212 patients with diabetes were included. The use of telehealth services was associated with an increase in outpatient visits in those with hypertension (0.07, p = 0.0027) and diabetes (0.32, p < 0.0001). A decrease in hospitalizations (-0.2%, p = 0.0007) and emergency department visits (-0.11%, p = 0.0016) was found in individuals with hypertension. Policy implementation also resulted in an increase in medication possession ratio (MPR) and the proportion of appropriate prescription in patients with hypertension (MPR: 3.0%, p < 0.0001, prescription: 3.1%, p < 0.0001) and diabetes (MPR: 3.4%, p < 0.0001, prescription: 1.7%, p < 0.0001). Conclusions: The findings confirm a relationship between implementing telehealth services and improved patterns of health care utilization and medication prescription, suggesting the potential benefit of telehealth in managing chronic diseases.

Liver Diseases in South Korea: A Pulse Check of the Public's Knowledge, Awareness, and Behaviors.

PURPOSE: National surveys in Korea have spotlighted suboptimal levels of awareness among the public towards liver-related health and diseases, leading to progressive reform of national policies and education efforts. This study aimed to assess the status of the Korean public's knowledge towards liver-related diseases. MATERIALS AND METHODS: A self-reported, cross-sectional, web-based questionnaire study was conducted between February-March 2020 among 1000 Korean adults. Questionnaire items assessed the knowledge, awareness, and behaviors towards liver-related health and diseases. RESULTS: About half (50.9%-52.1%) knew untreated/chronic viral hepatitis could lead to liver failure and/or cancer. Misconceptions pertaining to viral hepatitis transmission risks exist with only 26.3% knowing viral hepatitis B cannot be transmitted by dining with an infected individual. About one-fifth (22.2%) were aware of an available cure for viral hepatitis C. Less than half were aware of the risk factors associated with nonalcoholic steatohepatitis (NASH), despite 72.4% and 49.5% having heard of fatty liver disease and NASH, respectively. More than one-third were unlikely to seek medical consultation even if exposed to viral hepatitis risk factors or upon diagnosis with a liver condition. Reasons for this low urgency included costs-related concerns, perceptions of being healthy, and the viewpoint that the condition is not life-threatening. CONCLUSION: The public's knowledge towards liver-related diseases in Korea was found to be lacking, which could account for a lower sense of urgency towards screening and treatment. More efforts are needed to address misperceptions and dispel stigma in an effort to encourage pro-health seeking behaviors.

Extract of Moutan radicis cortex and Cinnamomi ramulus ameliorates laser-induced choroidal neovascularization in Brown-Norway rats.

BACKGROUND: Moutan radicis cortex (MRC) and Cinnamomi ramulus (CR) are commonly used in eastern Asian traditional medicine to treat various diseases including cerebrovascular and cardiovascular, and have wide spectrum of pharmacological activities. However, the effect against laser-induced choroidal neovascularization (CNV) of extract of MRC and CR (1:1) (MRCCR) has not yet been studied. PURPOSE: Our aim was to investigate the inhibitory effect of MRCCR on pathological CNV in laser-treated Brown-Norway (BN) rats. METHODS: MRCCR (60, 90 mg/kg) was orally administered twice per day for 15 days from the day of CNV formation in laser-treated BN rats. Effects of MRCCR or its constituents on cell migration, tube formation, hyperpermeability and phosphorylation of FAK/p38 MAPK were confirmed in humane retinal microvascular endothelial cells or human retinal pigment epithelial cells. RESULTS: MRCCR significantly reduced the CNV lesions areas and the extent of fluorescein leakage. MRCCR and its constituents such as ellagic acid, paeonol or gallic acid decreased cell migration, tube formation or hyperpermeability. MRCCR inhibited the phosphorylation of FAK and p38 MAPK. CONCLUSION: Combining the oral MRCCR and intravitreal injection of anti-VEGF medicine may result in a more potent therapeutic effect and consequently bring the reduction in eye injection numbers for patients with wet AMD.

Imbalance in Cardiovascular Surgery Medical Service Use Between Regions.

BACKGROUND: This study uses the relevance index to understand the condition of regional medical service use for cardiovascular surgery and to identify the medical service use imbalance between regions. METHODS: This study calculated the relevance index of 16 metropolitan cities and provinces using resident registration address data from the Ministry of Government Administration and Home Affairs and the 2010-2014 health insurance, medical care assistance, and medical benefits claims data from the Health Insurance Review and Assessment Service. We identified developments over the 5-year time period and analyzed the level of regional imbalance regarding cardiovascular surgery through the relative comparison of relevance indexes between cardiovascular and other types of surgery. RESULTS: The relevance index was high in large cities such as Seoul, Daegu, and Gwangju, but low in regions that were geographically far from the capital area, such as the Gangwon and Jeju areas. Relevance indexes also fell as the years passed. Cardiovascular surgery has a relatively low relevance index compared to key types of surgery of other fields, such as neurosurgery and colorectal surgery. CONCLUSION: This study identified medical service use imbalance between regions for cardiovascular surgery. Results of this study demonstrate the need for political intervention to enhance the accessibility of necessary special treatment, such as cardiovascular surgery.

The Association Between Treatment Frequency and Treatment Outcome for Cardiovascular Surgeries.

BACKGROUND: This study analyzed the association between the volume of heart surgeries and treatment outcomes for hospitals in the last five years. METHODS: Hospitals that perform heart surgeries were chosen throughout Korea as subjects using from the Health Insurance Review and Assessment Service. The treatment outcome of the heart surgeries was defined as the mortality within 30 postoperative days, while the annual volume of the surgeries was categorized. Logistic regression was used as the statistical analysis method, and the impacts of the variables on the heart surgery treatment outcomes were then analyzed. RESULTS: The chance of death of patients who received surgery in a hospital that performed 50 or more surgeries annually was noticeably lower than patients receiving operations from hospitals that performed fewer than 50 surgeries annually, indicating that the chance of death decreases as the annual volume of heart surgeries in the hospital increases. In particular, the mortality rate in hospitals that performed more than 200 surgeries annually was less than half of that in hospitals that performed 49 or fewer surgeries annually. CONCLUSION: These results indicate that accumulation of a certain level of heart surgery experience is critical in improving or maintaining the quality of heart surgeries. In order to improve the treatment outcomes of small hospitals, a support policy must be implemented that allows for cooperation with experienced professionals.

Development of Models for Regional Cardiac Surgery Centers.

BACKGROUND: This study aimed to develop the models for regional cardiac surgery centers, which take regional characteristics into consideration, as a policy measure that could alleviate the concentration of cardiac surgery in the metropolitan area and enhance the accessibility for patients who reside in the regions. METHODS: To develop the models and set standards for the necessary personnel and facilities for the initial management plan, we held workshops, debates, and conference meetings with various experts. RESULTS: After partitioning the plan into two parts (the operational autonomy and the functional comprehensiveness), three models were developed: the 'independent regional cardiac surgery center' model, the 'satellite cardiac surgery center within hospitals' model, and the 'extended cardiac surgery department within hospitals' model. Proposals on personnel and facility management for each of the models were also presented. A regional cardiac surgery center model that could be applied to each treatment area was proposed, which was developed based on the anticipated demand for cardiac surgery. The independent model or the satellite model was proposed for Chungcheong, Jeolla, North Gyeongsang, and South Gyeongsang area, where more than 500 cardiac surgeries are performed annually. The extended model was proposed as most effective for the Gangwon and Jeju area, where more than 200 cardiac surgeries are performed annually. CONCLUSION: The operation of regional cardiac surgery centers with high caliber professionals and quality resources such as optimal equipment and facility size, should enhance regional healthcare accessibility and the quality of cardiac surgery in South Korea.

Projections of Demand for Cardiovascular Surgery and Supply of Surgeons.

BACKGROUND: While demand for cardiovascular surgery is expected to increase gradually along with the rapid increase in cardiovascular diseases with respect to the aging population, the supply of thoracic and cardiovascular surgeons has been continuously decreasing over the past 10 years. Consequently, this study aims to achieve guidance in establishing health care policy by analyzing the supply and demand for cardiovascular surgeries in the medical service area of Korea. METHODS: After investigating the actual number of cardiovascular surgeries performed using the National Health Insurance claim data of the Health Insurance Review and Assessment Service, as well as drawing from national statistics concerning the elderly population aged 65 and over, this study estimated the number of future cardiovascular surgeries by using a cell-based model. To be able to analyze the supply and demand of surgeons, the recent status of new surgeons specializing in thoracic and cardiovascular surgeries and the ratio of their subspecialties in cardiovascular surgeries were investigated. Then, while taking three different scenarios into account, the number of cardiovascular surgeons expected be working in 5-year periods was projected. RESULTS: The number of cardiovascular surgeries, which was recorded at 10,581 cases in 2014, is predicted to increase consistently to reach a demand of 15,501 cases in 2040-an increase of 46.5%. There was a total of 245 cardiovascular surgeons at work in 2014. Looking at 5 year spans in the future, the number of surgeons expected to be supplied in 2040 is 184, to retire is 249, and expected to be working is 309-an increase of -24.9%, 1.6%, and 26.1%, respectively compared to those in 2014. This forecasts a demand-supply imbalance in every scenario. CONCLUSION: Cardiovascular surgeons are the most central resource in the medical service of highly specialized cardiovascular surgeries, and fostering the surgeons requires much time, effort, and resources; therefore, by analyzing the various factors affecting the supply of cardiovascular surgeons, an active intervention of policies can be prescribed for the areas that have failed to meet the appropriate market distributions.

Structural modifications at the 6-position of thieno[2,3-d]pyrimidines and their effects on potency at FLT3 for treatment of acute myeloid leukemia.

Fms-like tyrosine kinase 3 (FLT3) is a well-known and important target for the treatment of acute myeloid leukemia (AML). A series of thieno[2,3-d]pyrimidine derivatives from a modification at the 6-position were synthesized to identify effective FLT3 inhibitors. Although compounds 1 and 2 emerged as promising FLT3 inhibitors among the synthesized compounds, both compounds exhibited poor metabolic stability in human and rat liver microsomes. Hence, further optimization was required for the discovery of FLT3 inhibitors, with a focus on improving metabolic stability. Compound 16d, which had structural modifications of the methyl group at the 5-position and the 4-(2-methylaminoethoxy) phenyl group at the 6-position, exhibited good inhibitory activity against FLT3 and showed effective antiproliferative activity against four leukemia cell lines, including MV4-11. Moreover, compound 16d displayed enhanced metabolic stability. The results of this study indicated that 16d could be a promising compound for further optimization and development as a potent FLT3 inhibitor.

Synthesis and biological evaluation of novel thieno[2,3-d]pyrimidine-based FLT3 inhibitors as anti-leukemic agents.

The most common mutations in acute myeloid leukemia (AML) are those that cause the activation of FMS-like tyrosine kinase 3 (FLT3). Therefore, FLT3 is regarded as a potential target for the treatment of AML. A novel series of thieno[2,3-d]pyrimidine-based analogs was designed and synthesized as FLT3 inhibitors. All synthesized compounds were assayed for the tyrosine kinase activity of FLT3 and growth inhibitory activity in four human leukemia cell lines (THP1, MV4-11, K562, and HL-60). Among these compounds, compound 17a, which possesses relatively short and simple substituents at the C6 position of thieno[2,3-d]pyrimidine, emerged as the most promising anti-leukemic agent. Compound 17a exhibited potent inhibition of FLT3-positive leukemic cell growth and of the FLT3 D835Y kinase; such inhibition is required for the successful treatment of AML. The data supports the further investigation of this class of compounds as potential anti-leukemic agents.

Discovery of thienopyrimidine-based FLT3 inhibitors from the structural modification of known IKKß inhibitors.

Inactivation of the NF-κB signaling pathway by inhibition of IKKß is a well-known approach to treat inflammatory diseases such as rheumatoid arthritis and cancer. Thienopyrimidine-based analogues were designed through modification of the known IKKß inhibitor, SPC-839, and then biologically evaluated. The resulting analogues had good inhibitory activity against both nitric oxide and TNF-α, which are well-known inflammatory responses generated by activated NF-κB. However, no inhibitory activity against IKKß was observed with these compounds. The thienopyrimidine-based analogues were subsequently screened for a target kinase, and FLT3, which is a potential target for acute myeloid leukemia (AML), was identified. Thienopyrimidine-based FLT3 inhibitors showed good inhibition profiles against FLT3 under 1µM. Overall, these compounds represent a promising family of inhibitors for future development of a treatment for AML.

Human Kruppel-related 3 (HKR3) is a novel transcription activator of alternate reading frame (ARF) gene.

HKR3 (Human Krüppel-related 3) is a novel POK (POZ-domain Krüppel-like zinc-finger) family transcription factor. Recently, some of the POK (POZ-domain Krüppel-like zinc finger) family proteins have been shown to play roles in cell cycle arrest, apoptosis, cell proliferation, and oncogenesis. We investigated whether HKR3, an inhibitor of cell proliferation and an uncharacterized POK family protein, could regulate the cell cycle by controlling expression of genes within the p53 pathway (ARF-MDM2-TP53-p21WAF/CDKN1A). HKR3 potently activated the transcription of the tumor suppressor gene ARF by acting on the proximal promoter region (bp, -149∼+53), which contains Sp1 and FBI-1 binding elements (FREs). HKR3 interacted with the co-activator p300 to activate ARF transcription, which increased the acetylation of histones H3 and H4 within the proximal promoter. Oligonucleotide pull-down assays and ChIP assays revealed that HKR3 interferes with the binding of the proto-oncogenic transcription repressor FBI-1 to proximal FREs, thus derepressing ARF transcription.

Propionibacterium acnes Induces IL-1ß secretion via the NLRP3 inflammasome in human monocytes.

Propionibacterium acnes induction of inflammatory responses is a major etiological factor contributing to the pathogenesis of acne vulgaris. In particular, the IL-1 family of cytokines has a critical role in both initiation of acne lesions and in the inflammatory response in acne. In this study, we demonstrated that human monocytes respond to P. acnes and secrete mature IL-1ß partially via the NLRP3-mediated pathway. When monocytes were stimulated with live P. acnes, caspase-1 and caspase-5 gene expression was upregulated; however, IL-1ß secretion required only caspase-1 activity. P. acnes induced key inflammasome genes including NLRP1 and NLPR3. Moreover, silencing of NLRP3, but not NLRP1, expression by small interfering RNA attenuated P. acnes-induced IL-1ß secretion. The mechanism of P. acnes-induced NLRP3 activation and subsequent IL-1ß secretion was found to involve potassium efflux. Finally, in acne lesions, mature caspase-1 and NLRP3 were detected around the pilosebaceous follicles and colocalized with tissue macrophages. Taken together, our results indicate that P. acnes triggers a key inflammatory mediator, IL-1ß, via NLRP3 and caspase-1 activation, suggesting a role for inflammasome-mediated inflammation in acne pathogenesis.

Propionibacterium acnes Induces an IL-17 Response in Acne Vulgaris that Is Regulated by Vitamin A and Vitamin D.

Acne vulgaris is the most common skin disorder affecting millions of people worldwide and inflammation resulting from the immune response targeting Propionibacterium acnes has a significant role in its pathogenesis. In this study, we have demonstrated that P. acnes is a potent inducer of T helper 17 (Th17) and Th1, but not Th2 responses in human peripheral blood mononuclear cells (PBMCs). P. acnes stimulated expression of key Th17-related genes, including IL-17A, RORα, RORc, IL-17RA, and IL-17RC, and triggered IL-17 secretion from CD4(+), but not from CD8(+) T cells. Supernatants from P. acnes-stimulated PBMCs were sufficient to promote the differentiation of naive CD4(+)CD45RA T cells into Th17 cells. Furthermore, we found that the combination of IL-1ß, IL-6, and transforming growth factor-ß-neutralizing antibodies completely inhibited P. acnes-induced IL-17 production. Importantly, we showed that IL-17-expressing cells were present in skin biopsies from acne patients but not from normal donors. Finally, vitamin A (all-trans retinoic acid) and vitamin D (1,25-dihydroxyvitamin D3) inhibited P. acnes-induced Th17 differentiation. Together, our data demonstrate that IL-17 is induced by P. acnes and expressed in acne lesions and that both vitamin A and D could be effective tools to modulate Th17-mediated diseases such as acne.

Effects of Allium victorialis leaf extracts and its single compounds on aldose reductase, advanced glycation end products and TGF-ß1 expression in mesangial cells.

BACKGROUND: Accumulating evidences suggest that aldose reductase (AR) inhibitors and advanced glycation end product (AGE) formation inhibitors may prevent chronic hyperglycemia-induced long-term complication in diabetes. Transforming growth factor-beta1 (TGF-ß1) plays an important role in the development of diabetic nephropathy. Allium species have been utilized in folk medicine throughout the world for the treatment of various physical disorders. However, the benefits of Allium victorialis (A. victorialis) against diabetic complications, especially nephropathy, have yet to be explored. In the present study, we investigated the protective effect of the compounds isolated from A. victorialis leaf on diabetic nephropathy. METHODS: In vitro AR activity, AGEs formation, and AGE-receptor for AGEs (RAGE) binding in human RAGE (hRAGE)-overexpressing cells were tested. High glucose-induced transforming growth factor-beta1 (TGF-ß1) expression was also examined in mouse kidney mesangial cells (MMCs) cultured under high glucose. RESULTS: Of the isolated eight compounds from A. victorialis leaf extracts tested, quercitrin exhibited the most pronounced inhibitory effects on AR activity (IC50 value of 0.17 µM) and AGEs formation (IC50 value of 4.20 µM). Furthermore, quercitrin disrupted AGE-RAGE binding in a concentration-dependent manner in hRAGE-overexpressing cells. Additionally, of the eight compounds tested, ferulic acid significantly reduced high glucose-induced TGF-ß1 expression and secretion in MMCs. CONCLUSIONS: Our results suggest that active compounds isolated from A. victorialis leaf exhibit inhibitory effects on AR activity in rat lenses and AGE formation. Further, ferulic acid reduces TGF-ß1 mRNA expression and secretion in MMCs under diabetic conditions. Thus, A. victorialis is a good candidate for the development of treatments for diabetic nephropathy.

The proto-oncoprotein FBI-1 interacts with MBD3 to recruit the Mi-2/NuRD-HDAC complex and BCoR and to silence p21WAF/CDKN1A by DNA methylation.

The tumour-suppressor gene CDKN1A (encoding p21Waf/Cip1) is thought to be epigenetically repressed in cancer cells. FBI-1 (ZBTB7A) is a proto-oncogenic transcription factor repressing the alternative reading frame and p21WAF/CDKN1A genes of the p53 pathway. FBI-1 interacts directly with MBD3 (methyl-CpG-binding domain protein 3) in the nucleus. We demonstrated that FBI-1 binds both non-methylated and methylated DNA and that MBD3 is recruited to the CDKN1A promoter through its interaction with FBI-1, where it enhances transcriptional repression by FBI-1. FBI-1 also interacts with the co-repressors nuclear receptor corepressor (NCoR), silencing mediator for retinoid and thyroid receptors (SMRT) and BCL-6 corepressor (BCoR) to repress transcription. MBD3 regulates a molecular interaction between the co-repressor and FBI-1. MBD3 decreases the interaction between FBI-1 and NCoR/SMRT but increases the interaction between FBI-1 and BCoR. Because MBD3 is a subunit of the Mi-2 autoantigen (Mi-2)/nucleosome remodelling and histone deacetylase (NuRD)-HDAC complex, FBI-1 recruits the Mi-2/NuRD-HDAC complex via MBD3. BCoR interacts with the Mi-2/NuRD-HDAC complex, DNMTs and HP1. MBD3 and BCoR play a significant role in the recruitment of the Mi-2/NuRD-HDAC complex- and the NuRD complex-associated proteins, DNMTs and HP. By recruiting DNMTs and HP1, Mi-2/NuRD-HDAC complex appears to play key roles in epigenetic repression of CDKN1A by DNA methylation.

Large dermal non neural granular cell tumor on the surgical wound site.

Granular cell tumors (GCTs) can be divided into neural type with S-100 reactivity and non-neural type without that. The latter has not been widely recognized and there are only fewer reports available when compared to conventional GCT. A 65-year-old man was presented with the presence of a painless mass on his back. The mass had developed into a small nodule on the scar developed because of previous surgery carried out 2 years ago. The tumor consisted of large, polygonal cells comprising of an enormous number of faintly eosinophilic small granules in the cytoplasm. The cytoplasmic granules were stained positively for periodic acid-Schiff stain. Immunohistochemical stains for S-100 protein and neuron-specific enolase were found to be negative. Herein, we report the appearance of a very rare case of non neural GCT developed on the surgical scar in support with relevant literature reviews.