Evaluating cardiovascular disease risk stratification using multiple-polygenic risk scores and pooled cohort equations: insights from a 17-year longitudinal Korean cohort study.

Cardiovascular disease (CVD) remains the leading cause of mortality worldwide, caused by a complex interplay of genetic and environmental factors. This study aimed to evaluate the combined efficacy of multi-polygenic risk scores and pooled cohort equations (PCE) for predicting future CVD risks in the Korean population. In this longitudinal study, 7,612 individuals from the Ansan and Ansung cohorts were analyzed over a 17-year follow-up period. The participants were genotyped using the Korea Biobank Array, and quality-controlled genetic data were subjected to imputation analysis. The weighted sum of the PRSs (wPRSsum) was calculated using PRS-CS with summary statistics from myocardial infarction, ischemic stroke, coronary artery disease, and hypertension genome-wide association studies. The recalibrated PCE was used to assess clinical risk, and the participants were stratified into risk groups based on the wPRSsum and PCE. Associations between these risk scores and incident CVD were evaluated using Cox proportional hazards models and Kaplan-Meier analysis. The wPRSsum approach showed a significant association with incident CVD (HR = 1.15, p = 7.49 × 10-5), and the top 20% high-risk genetic group had an HR of 1.50 (p = 5.04 × 10-4). The recalibrated PCE effectively differentiated between the low and high 10-year CVD risk groups, with a marked difference in survival rates. The predictive models constructed using the wPRSsum and PCE demonstrated a slight improvement in prediction accuracy, particularly among males aged <55 years (C-index = 0.640). We demonstrated that while the integration of wPRSsum with PCE did not significantly outperform the PCE-only model (C-index: 0.703 for combined and 0.704 for PCE-only), it provided enhanced stratification of CVD risk. The highest risk group, identified through the combination of high wPRSsum and PCE scores, exhibited an HR of 4.99 for incident CVD (p = 1.45 × 10-15). These findings highlight the potential of integrating genetic risk assessments with traditional clinical tools for effective CVD risk stratification. Although the addition of wPRSsum to the PCE provided a marginal predictive improvement, it proved valuable in identifying high-risk individuals and supporting personalized treatment strategies. This study reinforces the utility of multi-PRS in conjunction with clinical risk assessment tools, paving the way for more tailored approaches for CVD prevention and management in diverse populations.

Recent advances in photoelectrochemical hydrogen production using I-III-VI quantum dots.

Photoelectrochemical (PEC) water splitting, recognized for its potential in producing solar hydrogen through clean and sustainable methods, has gained considerable interest, particularly with the utilization of semiconductor nanocrystal quantum dots (QDs). This minireview focuses on recent advances in PEC hydrogen production using I-III-VI semiconductor QDs. The outstanding optical and electrical properties of I-III-VI QDs, which can be readily tuned by modifying their size, composition, and shape, along with an inherent non-toxic nature, make them highly promising for PEC applications. The performance of PEC devices using these QDs can be enhanced by various strategies, including ligand modification, defect engineering, doping, alloying, and core/shell heterostructure engineering. These approaches have notably improved the photocurrent densities for hydrogen production, achieving levels comparable to those of conventional heavy-metal-based counterparts. Finally, this review concludes by addressing the present challenges and future prospects of these QDs, underlining crucial steps for their practical applications in solar hydrogen production.

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. Objectives: To elucidate roles of MCs and NCs in keloid pathogenesis and their correlation with disease activity. Methods: Keloid samples from chest and back regions were analyzed. Single-cell RNA sequencing (scRNA-seq) was conducted for six active keloids (AK) samples, four inactive keloids (IK) samples, and three mature scar (MS) samples from patients with keloids. Results: The scRNA-seq analysis demonstrated notable enrichment of MCs, lymphocytes, and macrophages in AKs, which exhibited continuous growth at the excision site when compared to IK and MS samples (P = 0.042). Expression levels of marker genes associated with activated and degranulated MCs, including FCER1G, BTK, and GATA2, were specifically elevated in keloid lesions. Notably, MCs within AK lesions exhibited elevated expression of genes such as NTRK1, S1PR1, and S1PR2 associated with neuropeptide receptors. Neural progenitor cell and non-myelinating Schwann cell (nmSC) genes were highly expressed in keloids, whereas myelinating Schwann cell (mSC) genes were specific to MS samples. Conclusions: scRNA-seq analyses of AK, IK, and MS samples unveiled substantial microenvironmental heterogeneity. Such heterogeneity might be linked to disease activity. These findings suggest the potential contribution of MCs and NCs to keloid pathogenesis. Histopathological and molecular features observed in AK and IK samples provide valuable insights into the mechanisms underlying pain and pruritus in keloid lesions.

Comparison of intraocular pressure fluctuation and glaucoma progression rate between phakic and pseudophakic eyes in pseudoexfoliation glaucoma.

The management of patients with concurrent pseudoexfoliation glaucoma (PXG) and cataract is challenging given its worse prognosis compared to other glaucoma types and the increased risk associated with cataract surgery. In this retrospective study, we investigated the long-term outcomes of cataract surgery in patients with PXG. We enrolled patients with PXG who had undergone cataract surgery at least 2 years previously and compared them with mean deviation (MD) matched patients with phakic eyes. The results showed that both groups experienced a decrease in MD, with the group of pseudophakic eyes exhibiting a significantly higher rate of decline (-2.15 ± 2.66 dB/year vs. -0.86 ± 0.95 dB/year; P = 0.040). Similarly, there was a trend towards more rapid thinning of the retinal nerve fiber layer in the pseudophakic group (-2.92 ± 2.34 µm/year vs. -1.79 ± 1.71 µm/year; P = 0.074). No significant differences in the intraocular pressure parameters were observed between the two groups. Multivariate analysis revealed that pseudophakic lens status was significantly associated with a faster rate of MD decline in patients with PXG (regression coefficient, -1.391; P = 0.022). These findings underscore the importance of close monitoring of patients with pseudophakic PXG to effectively manage glaucoma progression.

Comprehensive Evaluation of Traditional Herbal Medicine Combined With Adjuvant Chemotherapy on Post-Surgical Gastric Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Gastric cancer is a common cause of global mortality, with significant challenges during treatment due to side effects and complications. Traditional herbal medicine (THM) has emerged as a potential adjuvant therapy to enhance cancer treatment by reducing side effects and bolstering the immune response. This study conducted a meta-analysis to assess the efficacy and safety of THM as an adjuvant therapy in post-surgical gastric cancer patients. METHODS: PubMed, Cochrane Library, EMBASE, CNKI, CiNii, KMBASE, KISS, OASIS, RISS, and ScienceON databases were searched from inception through December, 2021. The outcomes considered in this analysis encompassed tumor response, quality of life (QoL), side effects, and tumor markers. Additionally, a frequency analysis of the most commonly used herbs in the included studies was conducted. A total of 36 randomized controlled trials (RCTs) were included, and data were extracted according to study design. The analysis compared groups receiving chemotherapy alone with those receiving both chemotherapy and THM treatment. RESULTS: The group receiving both chemotherapy and THM showed substantial improvement in tumor response compared to the chemotherapy-only control group (RR 1.25, 95% CI [1.09, 1.45]). QoL also significantly increased in the THM-treated group. Most drug adverse reactions displayed statistical significance, except for platelet reduction. Tumor markers CEA, CA19-9, and CA72-4 exhibited significant improvements, but CA125 did not. The 1, 2, and 3-year survival rates improved, with RR values of 1.08 (95% CI [1.02, 1.14]), 1.32 (95% CI [1.19, 1.47]), and 1.42 (95% CI [1.12, 1.79]) respectively. However, some publication bias was indicated. CONCLUSION: THM may offer potential benefits as a complementary approach to post-surgical anticancer therapy in gastric cancer patients. Improved tumor response, quality of life, and survival rates were reported. However, it is important to exercise caution due to the possibility of publication bias, and further research is needed to confirm these findings.Registration:PROSPERO CRD 42022354133.

CXCL10 upregulation in radiation-exposed human peripheral blood mononuclear cells as a candidate biomarker for rapid triage after radiation exposure.

PURPOSE: In case of a nuclear accident, individuals with high-dose radiation exposure (>1-2 Gy) should be rapidly identified. While ferredoxin reductase (FDXR) was recently suggested as a radiation-responsive gene, the use of a single gene biomarker limits radiation dose assessment. To overcome this limitation, we sought to identify reliable radiation-responsive gene biomarkers. MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from mice after total body irradiation, and gene expression was analyzed using a microarray approach to identify radiation-responsive genes. RESULTS: In light of the essential role of the immune response following radiation exposure, we selected several immune-related candidate genes upregulated by radiation exposure in both mouse and human PBMCs. In particular, the expression of ACOD1 and CXCL10 increased in a radiation dose-dependent manner, while remaining unchanged following lipopolysaccharide (LPS) stimulation in human PBMCs. The expression of both genes was further evaluated in the blood of cancer patients before and after radiotherapy. CXCL10 expression exhibited a distinct increase after radiotherapy and was positively correlated with FDXR expression. CONCLUSIONS: CXCL10 expression in irradiated PBMCs represents a potential biomarker for radiation exposure.

Pleomorphic dermal sarcoma presenting in a child with Li-Fraumeni syndrome: A case report and review of the literature.

Pleomorphic dermal sarcoma (PDS) is an uncommon malignant soft-tissue tumor that occurs mostly in elderly patients, with only 5% of cases occurring in children. However, pediatric patients with Li-Fraumeni syndrome (LFS) can develop several types of cancer, particularly sarcomas. Here, we describe a young LFS patient who presented with early-onset PDS and review the literature.

Application of optogenetic glial cells to neuron-glial communication.

Optogenetic techniques combine optics and genetics to enable cell-specific targeting and precise spatiotemporal control of excitable cells, and they are increasingly being employed. One of the most significant advantages of the optogenetic approach is that it allows for the modulation of nearby cells or circuits with millisecond precision, enabling researchers to gain a better understanding of the complex nervous system. Furthermore, optogenetic neuron activation permits the regulation of information processing in the brain, including synaptic activity and transmission, and also promotes nerve structure development. However, the optimal conditions remain unclear, and further research is required to identify the types of cells that can most effectively and precisely control nerve function. Recent studies have described optogenetic glial manipulation for coordinating the reciprocal communication between neurons and glia. Optogenetically stimulated glial cells can modulate information processing in the central nervous system and provide structural support for nerve fibers in the peripheral nervous system. These advances promote the effective use of optogenetics, although further experiments are needed. This review describes the critical role of glial cells in the nervous system and reviews the optogenetic applications of several types of glial cells, as well as their significance in neuron-glia interactions. Together, it briefly discusses the therapeutic potential and feasibility of optogenetics.

Effect of Traditional Korean Medicine Oncotherapy on the Survival, Quality of Life, and Telomere Length: A Prospective Cohort Study.

A 4-year prospective cohort study on patients with lung, gastric, hepatic, colorectal, breast, uterine, and ovarian cancer was conducted at the East-West Cancer Center (EWCC) of Daejeon Korean Medicine Hospital in Daejeon, Korea. We divided patients into 2 groups based on how long they had been receiving TKM oncotherapy and compared event-free survival (EFS), telomere length change, and quality of life (QoL). The study collected data on 83 patients from October 2016 to June 2020 and discovered no statistical differences in EFS based on the duration of TKM oncotherapy. In the analysis of changes in QoL outcomes, there were no statistically significant group differences between the groups. After controlling for covariates that could affect telomere length, the long-term TKM oncotherapy group had a higher daily telomere attrition rate. The study of the relationship between telomere length and prognostic factors discovered that patients with advanced N stage at the time of diagnosis and who had previously received radiotherapy had shorter telomere length. When examining associations between SNP genotype and percentile score of telomere length, this study was able to confirm an association between telomere length and rs4387287. This study is significant because it is the first to assess the effects of TKM oncotherapy and investigate telomere length-related factors. To assess the effects of TKM oncotherapy on cancer patients' survival and QoL, a longer-term observational study with a larger sample size is required.

Effects of Protein Hydrolysate from Silkworm (Bombyx mori) pupae on the C2C12 Myogenic Differentiation.

This study investigated the effects and active compounds of silkworm pupae, an edible insect, on C2C12 muscle differentiation. The protein of silkworm pupae was extracted using sonication after defatting with hexane. Subsequently, the extract was rehydrated using Alcalase to obtain a protein hydrolysate. The silkworm pupae protein hydrolysate effectively promoted C2C12 myogenic differentiation without cytotoxicity. Subsequently, the hydrolysate was fractionated into four subfractions using preparative high-performance liquid chromatography (Prep-HPLC). Subfraction 1 was the most effective in promoting C2C12 myogenic differentiation and significantly upregulated the expression of myoblast transcription factors, 1.5-fold of myoblast determination protein 1 (MyoD), 2-fold of myogenin, and 3-fold of myosin heavy chain (MyHC). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) and multivariate statistical analysis were used to identify the active peptides in silkworm pupae responsible for the observed effects; then, dipeptides and essential amino acids, such as isoleucine (Ile), valine (Val), and methionine (Met), were identified. In addition, Val, Ile, and two dipeptides underwent quantification to determine the potential bioactive peptides that enhanced C2C12 myogenic differentiation. This study suggests that the peptides from silkworm pupae could be used as a nutraceutical to enhance muscle growth.

An archaeal transcription factor EnfR with a novel 'eighth note' fold controls hydrogen production of a hyperthermophilic archaeon Thermococcus onnurineus NA1.

Thermococcus onnurineus NA1, a hyperthermophilic carboxydotrophic archaeon, produces H2 through CO oxidation catalyzed by proteins encoded in a carbon monoxide dehydrogenase (CODH) gene cluster. TON_1525 with a DNA-binding helix-turn-helix (HTH) motif is a putative repressor regulating the transcriptional expression of the codh gene cluster. The T55I mutation in TON_1525 led to enhanced H2 production accompanied by the increased expression of genes in the codh cluster. Here, TON_1525 was demonstrated to be a dimer. Monomeric TON_1525 adopts a novel 'eighth note' symbol-like fold (referred to as 'eighth note' fold regulator, EnfR), and the dimerization mode of EnfR is unique in that it has no resemblance to structures in the Protein Data Bank. According to footprinting and gel shift assays, dimeric EnfR binds to a 36-bp pseudo-palindromic inverted repeat in the promoter region of the codh gene cluster, which is supported by an in silico EnfR/DNA complex model and mutational studies revealing the implication of N-terminal loops as well as HTH motifs in DNA recognition. The DNA-binding affinity of the T55I mutant was lowered by ∼15-fold, for which the conformational change of N-terminal loops is responsible. In addition, transcriptome analysis suggested that EnfR could regulate diverse metabolic processes besides H2 production.

Epidemiology and survival analysis of Merkel cell carcinoma in South Korea: a nationwide, multicenter retrospective study.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer, of which most research has been conducted in Caucasians. Therefore, the clinicopathological features and prognosis of Merkel cell carcinoma in Asians are still scarce. The aim of this study is to investigate the epidemiology and survival of MCC in South Korea and provide representative information regarding MCC in Asia. METHODS: This was a retrospective, nationwide, multicenter study conducted in 12 centers across South Korea. Patients with pathologically proven MCC were included in the study. The clinicopathological features and clinical outcomes of the patients were investigated. Overall survival (OS) was analyzed using the Kaplan-Meier method, and independent prognostic factors were identified using Cox regression analysis. RESULTS: A total of 161 patients with MCC were evaluated. The mean age was 71 years with a female predominance. OS was significantly different among the stages. Among clinicopathological features, multivariate Cox regression analysis demonstrated that only the stage at diagnosis was associated with poorer overall survival. CONCLUSIONS: The results of our study suggest that the incidence of MCC was higher in females than in males and that there was a higher rate of local disease at the time of diagnosis. Among the variable clinicopathological features, disease stage at diagnosis was the only significant prognostic factor for MCC in South Korea. The findings of this nationwide, multicenter study suggest that MCC has distinct features in South Korea compared with other countries.

A Case of Cowden Syndrome Presenting with Diverse Cutaneous Manifestations.

Cowden syndrome is caused by mutations in the phosphatase and tensin homolog (PTEN) gene and is part of the PTEN hamartoma tumor syndrome. Skin lesions including trichilemmomas, acral keratosis, mucocunateous neuromas and oral paillomas are the most prevalent feature found in patients with Cowden syndrome. It also possesses an increased risk of developing malignancies including breast, thyroid, endometrial, and colorectal cancers. Due to the increased risk of cancer, early diagnosis and regular surveillance are important for Cowden syndrome patients. Herein, we report a case of Cowden syndrome with diverse cutaneous manifestations and thyroid cancer.

Longitudinal Changes in Peripapillary and Macular Vessel Densities in Glaucomatous Eyes With a Single-Hemifield Retinal Nerve Fiber Layer Defect.

PRCIS: The peripapillary vessel density decreased significantly in the affected hemiretina compared with that in the intact hemiretina in glaucomatous eyes with a single-hemifield retinal nerve fiber layer defect. PURPOSE: To evaluate the difference in the change rates of peripapillary vessel density (pVD) and macular vessel density (mVD) measured using optical coherence tomography angiography (OCTA) in glaucomatous eyes with a single-hemifield retinal nerve fiber layer (RNFL) defect. MATERIALS AND METHODS: We performed a retrospective, longitudinal study of 25 patients with glaucoma who were followed up for at least 3 years, with a minimum of 4 visits after baseline OCTA. At each visit, all participants underwent OCTA examination, and the pVD, mVD were measured by removing the large vessels. Changes in the pVD, mVD, peripapillary RNFL thickness (pRNFLT), and macular ganglion cell inner plexiform layer thickness were investigated in the affected and intact hemispheres, and the differences between the 2 hemispheres were compared. RESULTS: In the affected hemiretina, the pVD, mVD, pRNFLT, and mCGIPLT were reduced than that in the intact hemiretina (all, P < 0.001). The changes in pVD and mVD were statistically significant at the 2-year and 3-year follow-ups in the affected hemifield (all, P <0.05). However, pVD and mVD did not show statistically significant changes in the intact hemiretina throughout the follow-up visits. Although the pRNFLT decreased significantly at the 3-year follow-up, the macular ganglion cell inner plexiform layer thickness showed no statistical change at any follow-up visit. Compared with the intact hemisphere, pVD was the only parameter that showed significant changes throughout the follow-up period. CONCLUSION: Although pVD and mVD decreased in the affected hemiretina, the reduction in pVD was significant compared with that in the intact hemiretina.

Corrigendum: A Double-Blind, Split-Face, Randomized Study on the Effects and Safety of Intradermal Injection of Botulinum Toxin Type A 150 kD Neurotoxin in the Cheek.

This corrects the article on p. 442 in vol. 34, PMID: 36478426.

ABCA1-Mediated EMT Promotes Papillary Thyroid Cancer Malignancy through the ERK/Fra-1/ZEB1 Pathway.

Papillary thyroid cancer (PTC) is the most prevalent histological type of thyroid cancer (TC) worldwide. Although tumor metastasis occurs in regional lymph nodes, distant metastasis (DM) may also occur. Radioactive iodine (RAI) therapy is an effective treatment for TC; however, resistance to RAI occurs in patients with DM. Therefore, in this study, we investigated the efficacy of DM-related biomarkers as therapeutic targets for PTC therapy. ABCA1 expression was higher in aggressive BCPAP cells than in other PTC cells in terms of migration and invasion capacity. The knockdown of ABCA1 substantially decreased the expression of the epithelial-mesenchymal transition (EMT) marker, N-cadherin, and EMT regulator (ZEB1), resulting in suppressed migration and invasion of BCPAP cells. ABCA1 knockdown also reduced ERK activity and Fra-1 expression, which correlated with the effects of an ERK inhibitor or siRNA-mediated inhibition of ERK or Fra-1 expression. Furthermore, ABCA1-knocked-down BCPAP cells suppressed cell migration and invasion by reducing Fra-1 recruitment to Zeb1 promoter; lung metastasis was not observed in mice injected with ABCA1-knocked-down cells. Overall, our findings suggest that ABCA1 regulates lung metastasis in TC cells.