Gochujang, a traditional Korean fermented food, protects through suppressed inflammatory pathways and histological structure disruption in dextran sodium sulfate (DSS)-induced colitis mice.

The mechanisms underlying chronic inflammatory diseases remain unclear. Therefore, researchers have explored the mechanisms underlying colitis using diverse materials. Recently, there has been an increasing interest in fermented products and bioconversion materials, their potential efficacy is being actively studied. Gochujang, a traditional Korean fermented product, is crafted by blending fermented Meju powder, gochu (Korean chili) powder, glutinous rice, and salt. In our study, we explored the effectiveness of Gochujang (500 mg/kg; Cheongju and Hongcheon, Korea) in dextran sulfate sodium (DSS)-induced colitis mice model. Gochujang was orally administered for 2 weeks, followed by the induction of colitis using 3% DSS in the previous week. During our investigation, Gochujang variants (TCG22-25, Cheongju and TCG22-48, Hongcheon) did not exhibit significant inhibition of weight reduction (p = 0.061) but notably (p = 0.001) suppressed the reduction in large intestine length in DSS-induced colitis mice. In the serum from colitis mice, TCG22-48 demonstrated reduced levels of the inflammatory cytokines interleukin (IL)-6 (p = 0.001) and tumor necrosis factor (TNF)-α (p = 0.001). Additionally, it inhibited the phosphorylation of Erk (p = 0.028), p38, and NF-κB (p = 0.001) the inflammatory mechanism. In our study, TCG22-25 demonstrated a reduction in the IL-6 level (p = 0.001) in serum and inhibited the phosphorylation of p38 and NF-κB (p = 0.001). Histological analysis revealed a significant (p = 0.001) reduction in the pathological score of the large intestine from TCG22-25 and TCG22-48. In conclusion, the intake of Gochujang demonstrates potent anti-inflammatory effects, mitigating colitis by preventing the large intestine length reduction of animals with colitis, lowering serum levels of TNF-α and IL-6 cytokines, and inhibiting histological disruption and inflammatory mechanism phosphorylation.

Optimizing Percutaneous Mitral Valvuloplasty for Rheumatic Mitral Stenosis　- Clinical Significance of Changes in Mitral Valve Area.

BACKGROUND: Percutaneous mitral valvuloplasty (PMV) is a standard treatment for severe rheumatic mitral stenosis (RMS). However, the prognostic significance of the change in mitral valve area (∆MVA) during PMV is not fully understood.Methods and Results: This study analyzed data from the Multicenter mitrAl STEnosis with Rheumatic etiology (MASTER) registry, which included 3,140 patients with severe RMS. We focused on patients with severe RMS undergoing their first PMV. Changes in echocardiographic parameters, including MVA quantified before and after PMV, and composite outcomes, including mitral valve reintervention, heart failure admission, stroke, and all-cause death, were evaluated. An optimal result was defined as a postprocedural MVA ≥1.5 cm2without mitral regurgitation greater than Grade II. Of the 308 patients included in the study, those with optimal results and ∆MVA >0.5 cm² had a better prognosis (log-rank P<0.001). Patients who achieved optimal results but with ∆MVA ≤0.5 cm² had a greater risk of composite outcomes than those with optimal outcomes and ∆MVA >0.5 cm² (nested Cox regression analysis, hazard ratio 2.27; 95% confidence interval 1.09-4.73; P=0.028). CONCLUSIONS: Achieving an increase in ∆MVA of >0.5 cm2was found to be correlated with improved outcomes. This suggests that, in addition to achieving traditional optimal results, targeting an increase in ∆MVA of >0.5 cm2could be a beneficial objective in PMV treatment for RMS.

Clinical characteristics of persistent postural-perceptual dizziness and its visual subtype in Korean patients: A multicenter cross-sectional study.

OBJECTIVES: Persistent postural-perceptual dizziness (PPPD) is a chronic functional vestibular disorder for which the Bárány Society has established diagnostic criteria. This nationwide multicenter study aims to investigate the clinical features of individuals with definite PPPD and clinical variant PPPD who do not fully meet the diagnostic criteria, with a particular focus on visual exaggeration. METHODS: Between September 2020 and September 2021, a total of 76 individuals with definite PPPD and 109 individuals with clinical variant PPPD who did not meet all three exacerbating factors outlined in Criterion B were recruited from 18 medical centers in South Korea. The study gathered information on demographic factors, clinical manifestations, balance scales, and personality assessments. RESULTS: Comparative analysis between groups with definite PPPD and clinical variant with visual exacerbation revealed no significant differences in sociodemographic characteristics, clinical course, dizziness impact, and specific precipitants. Only disease duration was significantly longer in definite PPPD compared with variant with visual exacerbation. However, the variant without visual exacerbation displayed significantly reduced rates of panic disorder, diminished space-motion discomfort, lesser impact of dizziness, and decreased prevalence of depression when compared with the definitive PPPD. CONCLUSION: This is the first comprehensive nationwide study examining clinical features of both definite PPPD patients and its clinical variants, considering visual exacerbating factors. Differences in dizziness and personality traits emerged between definite PPPD and its potential variant without visual issues. Our results highlight the possibility of a distinct clinical variant of PPPD influenced by visual dependency.

Disseminating Necrotizing Leukoencephalopathy Associated With Intra-CSF Methotrexate Chemotherapy: A Retrospective Observational Study.

BACKGROUND AND OBJECTIVES: Leptomeningeal metastases (LMs) are neoplasms that proliferate to membranes lining the brain and spinal cord. Intra-CSF methotrexate (MTX) chemotherapy is a prevalent treatment option. However, resultant long-term neurotoxicity can lead to irreversible disseminated necrotizing leukoencephalopathy (DNL). This study aims to determine the incidence, characteristics, risk factors, and outcomes of DNL following intra-CSF MTX chemotherapy for LM. METHODS: We retrospectively reviewed patients with LM who received intra-CSF MTX between 2001 and 2021 at the National Cancer Center of Korea. Patients with a follow-up duration of <3 months and those without follow-up MRI after MTX administration were excluded. The primary outcome was the development of DNL, evaluated based on the clinical and radiologic definitions of DNL. Logistic and Cox proportional regression models were used to assess the risk of DNL in patients with LM receiving intra-CSF MTX chemotherapy. RESULTS: Of the 577 patients included in the DNL investigation, 13 (2.3%) were identified to have irreversible DNL. The MRI features of DNL typically include necrotic changes in the bilateral anterior temporal region, extensive white matter, and/or brainstem lesions. All patients with DNL experienced fatal clinical course despite MTX cessation. Logistic regression analysis revealed that a cumulative dose of MTX significantly affected DNL occurrence. Multivariable analysis showed that the factor of ≥10 MTX rounds was significant for DNL development after adjusting for route of MTX administration and prior brain radiotherapy (odds ratio 7.32, 95% CI 1.42-37.77 at MTX rounds ≥10 vs < 10). In the Cox proportional hazards model considering time to occurrence of DNL, ≥10 rounds of MTX were identified as an independent predictor of DNL (hazard ratio 12.57, 95% CI 1.62-97.28, p = 0.015), even after adjusting for the synergistic effect of brain radiotherapy. DISCUSSION: DNL is a rare but fatal complication of intra-CSF MTX chemotherapy, and its progression cannot be prevented despite early recognition. The cumulative dose of intra-CSF MTX was an independent risk factor for DNL occurrence. Thus, intra-CSF MTX treatment for patients with LM should be administered with caution considering the possibility of the cumulative irreversible neurotoxicity.

The effect of different LED wavelengths on the components and biosynthesis of isoflavonoid in sprout Astragalus membranaceus.

An artificial light source is the optimal element for studying the usability of the medicinal plant Astragalus membranaceus as a sprout vegetable. Based on artificial light source conditions, formononetin (FO) level was the highest (2.6 mg/L) in A. membranaceus exposed to white light emitting diode (LED) light, and calycosin (CA) level was the highest (3.09 mg/L) in the plant exposed to red LED light. According to the publicly available transcriptome data of LED-exposed sprout A. membranaceus LED, reference genes related to the content enhancement of FO, an isoflavone compound, and those related to the content enhancement of CA were selected. The expression patterns of these genes were assayed using qPCR. Among the genes related to FO enhancement, Gene-225190T showed the highest mRNA levels in cells of LED-white light-exposed sprout A. membranaceus; among the genes related to CA enhancement, Gene_042770T showed the highest expression under red LED light. Most genes related to the overall biosynthesis regulation of flavonoids of the upper concept of isoflavone were highly expressed in response to red LED light, and the transcriptional level of 4CL in response to red LED light was the highest. Based on these results, the artificial light sources that regulated the FO and CA contents in sprouts A. membranaceus were white and red LED lights, and the selected reference genes were capable of regulating isoflavone biosynthesis.

Krill oil inhibited adipogenic differentiation by inducing the nuclear Nrf2 expression and the AMPK activity.

The current study investigated the antiadipogenic mechanism of krill oil from the 3T3-L1 adipocytes. The krill oil adhered to the criteria as a food standard by showing 50.8% of the total phospholipid, 5.27% myristic acid, and 1.63% linoleic acid. The lipid accumulation that was measured in the 3T3-L1 cells using oil red O staining was reduced up to 54% by the krill oil. The krill oil treatment reduced the adipogenic transcription factors by downregulating the sterol regulatory element binding protein 1 (SREBP1) and acetyl-CoA carboxylase (ACC), phospho-ACC, and AMP-activated protein kinase (AMPK) phosphorylation. The current study confirmed that the krill oil inhibited adipogenesis by downregulating SREBP1 and ACC via the upregulation of the AMPK and nuclear factors E2-related factor 2 (Nrf2) signaling pathway in the 3T3-L1 adipocytes. These findings suggest that krill oil is a good source of phospholipid and phosphatidylcholine, which could be a potential natural antiobesity ingredient by inhibiting adipogenesis.

Bidirectional connectivity alterations in schizophrenia: a multivariate, machine-learning approach.

Objective: It is well known that altered functional connectivity is a robust neuroimaging marker of schizophrenia. However, there is inconsistency in the direction of alterations, i.e., increased or decreased connectivity. In this study, we aimed to determine the direction of the connectivity alteration associated with schizophrenia using a multivariate, data-driven approach. Methods: Resting-state functional magnetic resonance imaging data were acquired from 109 individuals with schizophrenia and 120 controls across two openly available datasets. A whole-brain resting-state functional connectivity (rsFC) matrix was computed for each individual. A modified connectome-based predictive model (CPM) with a support vector machine (SVM) was used to classify patients and controls. We conducted a series of multivariate classification analyses using three different feature sets, increased, decreased, and both increased and decreased rsFC. Results: For both datasets, combining information from both increased and decreased rsFC substantially improved prediction accuracy (Dataset 1: accuracy = 70.2%, permutation p = 0.001; Dataset 2: accuracy = 64.4%, permutation p = 0.003). When tested across datasets, the prediction model using decreased rsFC performed best. The identified predictive features of decreased rsFC were distributed mostly in the motor network for both datasets. Conclusion: These findings suggest that bidirectional alterations in rsFC are distributed in schizophrenia patients, with the pattern of decreased rsFC being more similar across different populations.

Deep-learning model for predicting physical fitness in possible sarcopenia: analysis of the Korean physical fitness award from 2010 to 2023.

Introduction: Physical fitness is regarded as a significant indicator of sarcopenia. This study aimed to develop and evaluate a deep-learning model for predicting the decline in physical fitness due to sarcopenia in individuals with potential sarcopenia. Methods: This study used the 2010-2023 Korean National Physical Fitness Award data. The data comprised exercise- and health-related measurements in Koreans aged >65 years and included body composition and physical fitness variables. Appendicular muscle mass (ASM) was calculated as ASM/height2 to define normal and possible sarcopenia. The deep-learning model was created with EarlyStopping and ModelCheckpoint to prevent overfitting and was evaluated using stratified k-fold cross-validation (k = 5). The model was trained and tested using training data and validation data from each fold. The model's performance was assessed using a confusion matrix, receiver operating characteristic curve, and area under the curve. The average performance metrics obtained from each cross-validation were determined. For the analysis of feature importance, SHAP, permutation feature importance, and LIME were employed as model-agnostic explanation methods. Results: The deep-learning model proved effective in distinguishing from sarcopenia, with an accuracy of 87.55%, precision of 85.57%, recall of 90.34%, and F1 score of 87.89%. Waist circumference (WC, cm), absolute grip strength (kg), and body fat (BF, %) had an influence on the model output. SHAP, LIME, and permutation feature importance analyses revealed that WC and absolute grip strength were the most important variables. WC, figure-of-8 walk, BF, timed up-and-go, and sit-and-reach emerged as key factors for predicting possible sarcopenia. Conclusion: The deep-learning model showed high accuracy and recall with respect to possible sarcopenia prediction. Considering the need for the development of a more detailed and accurate sarcopenia prediction model, the study findings hold promise for enhancing sarcopenia prediction using deep learning.

Is single incision laparoscopic surgery (SILS) for gastric gastrointestinal stromal tumor (GIST) dependent on the location of the tumor?

BACKGROUND: We compared the surgical outcomes of single-incision laparoscopic surgery (SILS) and conventional laparoscopic surgery (CLS) for gastric gastrointestinal stromal tumor (GIST). METHODS: We performed single-incision gastric wedge resection on prospectively-enrolled 15 consecutive patients with gastric GIST between November 2020 and April 2022 in a single tertiary center. The early perioperative outcomes of these patients were compared to those of patients who underwent CLS. The indications did not differ from those for conventional laparoscopic procedures for gastric GIST. RESULTS: In total, 30 patients were assigned to the SILS (n = 15) and CLS (n = 15) groups. There were no significant differences in the estimated blood loss and intraoperative blood transfusion between the SILS and CLS groups. There were no intraoperative complications or conversions to multiple-port or open surgery in the SILS group. Proximally located tumors were more commonly treated with CLS than with SILS (P = 0.045). GISTs located in the greater curvature were more commonly treated with SILS than with CLS, although the difference was not statistically significant (P = 0.08). The mean incision length in the SILS group was 4.1 cm shorter than that in the CLS group (3.2 ± 0.7 and 7.3 ± 5.2 cm, respectively, P = 0.01). The postoperative analgesic dose was significantly lower in the SILS than in the CLS group (0.4 ± 1.4 and 2.1 ± 2.3, respectively P = 0.01). Also, the duration of postoperative use of analgesic was shorter in SILS than in CLS (0.4 ± 0.7 and 2.0 ± 1.8, respectively, P = 0.01). There were no significant differences in the early postoperative complications between the groups. CONCLUSIONS: SILS is as safe, feasible, and effective for the treatment of gastric GIST as CLS with comparable postoperative complications, pain, and cosmesis. Moreover, SILS can be considered without being affected by the type or location of the tumor.

Does Epstein-Barr virus-positive gastric cancer establish a significant relationship with the multiple genes related to gastric carcinogenesis?

Gastric cancer has been categorized into molecular subtypes including Epstein-Barr virus (EBV)-positive tumors, which provide clinicopathological and prognostic information. In this study, we investigated the EBV infection status of patients with gastric cancer and its correlation with the clinicopathological characteristics and multiple genes related to gastric carcinogenesis. The data of 460 gastric cancer patients who underwent curative gastrectomy with D2 lymph node dissection between January 2017 and February 2022 were analyzed. The clinicopathological features and prognosis of the patients with EBV-positive gastric cancers were compared with those of EBV-negative gastric cancers. Immunohistochemistry for epidermal growth factor receptor (EGFR), C-erb B2, Ki-67, and p53 was performed. Additionally, in situ hybridization was conducted to detect EBV, and microsatellite instability (MSI) analysis was used to assess the deficiency in mismatch repair (MMR) genes. EBV-positivity and MSI were identified in 10.4% and 37.3% of gastric cancer patients, respectively. EBV positivity was associated with male gender (P = 0.001), proximal location (P = 0.004), poorly differentiated histological type (P = 0.048), moderate to severe lymphoid stroma (P = 0.006), high Ki-67 expression (P = 0.02), and a shorter resection margin. EGFR was more often expressed in EBV-negative gastric cancers (P < 0.001). MSI tumors were associated with older age (P = 0.01), the presence of lymphatic invasion (P = 0.02), less perineural invasion (P = 0.05), and the presence of H. pylori infection (P = 0.05). EBV positive gastric cancer is associated with increased Ki-67 and decreased EGFR expression and a shorter resection margin due to the prominent lymphoid stroma. However, MMR deficiency is not associated with EBV status even though MSI gastric cancer is related to H. pylori status.

Cellular Morphology and Transcriptome Comparative Analysis of Astragalus membranaceus Bunge Sprouts Cultured In Vitro under Different LED Light.

Astragalus membranaceus, the major components of which are saponins, flavonoids, and polysaccharides, has been established to have excellent pharmacological activity. After ginseng, it is the second most used medicinal plant. To examine the utility of A. membranaceus as a sprout crop for plant factory cultivation, we sought to establish a functional substance control model by comparing the transcriptomes of sprouts grown in sterile, in vitro culture using LED light sources. Having sown the seeds of A. membranaceus, these were exposed to white LED light (continuous spectrum), red LED light (632 nm, 1.58 µmol/m2/s), or blue LED light (465 nm, 1.44 µmol/m2/s) and grown for 6 weeks; after which, the samples were collected for transcriptome analysis. Scanning electron microscopy analysis of cell morphology in plants exposed to the three light sources revealed that leaf cell size was largest in those plants exposed to red light, where the thickest stem was observed in plants exposed to white light. The total number of genes in A. membranaceus spouts determined via de novo assembly was 45,667. Analysis of differentially expressed genes revealed that for the comparisons of blue LED vs. red LED, blue LED vs. white LED, and red LED vs. white LED, the numbers of upregulated genes were 132, 148, and 144, respectively. Binding, DNA integration, transport, phosphorylation, DNA biosynthetic process, membrane, and plant-type secondary cell wall biogenesis were the most enriched in the comparative analysis of blue LED vs. red LED, whereas Binding, RNA-templated DNA biosynthetic process, DNA metabolic process, and DNA integration were the most enriched in the comparative analysis of blue vs. white LED, and DNA integration and resolution of meiotic recombination intermediates were the most enrichment in the comparison between red LED vs. white LED. The GO term associated with flavonoid biosynthesis, implying the functionality of A. membranaceus, was the flavonoid biosynthetic process, which was enriched in the white LED vs. red LED comparison. The findings of this study thus indicate that different LED light sources can differentially influence the transcriptome expression pattern of A. membranaceus sprouts, which can provide a basis for establishing a flavonoid biosynthesis regulation model and thus, the cultivation of high-functional Astragalus sprouts.

Totally robotic Roux-en-Y gastric bypass in a morbidly obese patient in Korea: a case report.

Robotic bariatric surgery renders it unnecessary for surgeons to manually apply torque while simplifying intracorporeal suturing. Surgeons can comfortably manipulate instruments. Also, the three-dimensional operative field is very clear. Unfortunately, robotic bariatric surgery is still not the first choice for morbidly obese patients in Korea because it currently is not covered by the National Healthcare Insurance system. In this video, we show the totally robotic Roux-en-Y gastric bypass conducted using robotic staplers, in a morbidly obese patient with diabetes mellitus and private medical insurance.

Torilis japonica Extract Suppresses the Induction of Atopic Inflammation.

As one of the major intractable allergic disorders, atopic inflammation is commonly accompanied by itching, dry skin, and inflammation. Atopic inflammation deteriorates the quality of life and has no fundamental cure, so it is crucial to urgently explore and develop natural resources for long-term treatment without any side effects. This study aimed to verify Torilis japonica extract (TJE)'s relieving effect and mechanism against atopic inflammation using skin cells and skin equivalent models, as well as to investigate torilin's effect (obtained from TJE) and other unknown components as marker compounds. Torilin concentration was verified in TJE using high-performance liquid chromatography and analyzed the unknown components using nuclear magnetic resonance spectroscopy. Furthermore, TJE's cytotoxicity, regenerative effect, and cell cycle regulation effects were confirmed using skin cells with atopic inflammation (human dermal fibroblasts and HaCaT keratinocytes) by using TNF-α and IFN-γ treatments. Consequently, TJE was demonstrated to regulate TARC and CTACK expressions as chemokines and those of interleukin-4, -5, and -13 as cytokines related to atopic inflammation. TJE was further confirmed to affect the matrix metalloproteinase-1, -2, and -9 expressions, which are essential in skin damage. Lastly, this study confirmed TJE's relieving effect against atopic inflammation through a 3D skin model and RhCE model using human dermal fibroblasts and HaCaT keratinocytes. These findings on atopic inflammation verified torilin's relieving effects and TJE's other components.

Rosa gallica and its active compound, cyanidin-3,5-O-diglucoside, improve skin hydration via the GLK signaling pathway.

Rosa gallica has been previously reported to display anti-inflammatory, anti-oxidative, and anti-skin wrinkle activities. However, the effect of Rosa gallica on skin hydration and its active components are largely unknown. Herein, we aimed to investigate the skin hydration effect of rose petal extract (RPE) in humans and elucidate the underlying molecular mechanism. A double-blinded clinical study was performed to investigate the effect of RPE on skin hydration. Stratum corneum moisture analysis demonstrated that RPE treatment significantly improved hydration levels in human skin. Furthermore, HAS2 and hyaluronic acid levels were notably increased by RPE in keratinocytes and 3D human skin equivalent model. By comparing the modulatory effect on HAS2 expression, cyanidin-3,5-O-diglucoside (CDG) was identified as the most potent compound in RPE likely responsible for skin hydration. The kinase activity of GLK, an upstream regulator of MAPK signaling, was increased by CDG in a dose-dependent manner. Importantly, silencing GLK reversed CDG-mediated HAS2 upregulation, further supporting the involvement of GLK in the CDG-mediated effects. Binding of CDG to GLK was confirmed by pull-down assay and computer modeling. These findings suggest that RPE and its active component CDG increases skin hydration by upregulating HAS2 expression through modulating the GLK-MAP2K-MAPK signaling pathway.

Evaluation of Growth Characteristics and Biological Activities of 'Dachul', a Hybrid Medicinal Plant of Atractylodes macrocephala × Atractylodes japonica, under Different Artificial Light Sources.

This study was conducted to evaluate the effects of different artificial light sources on the growth characteristics and various biological activities of the Atractylodes macrocephala x Atractylodes japonica hybrid cv. 'Dachul', which is highly useful for medicinal purposes. The plant had the largest biomass with a plant height of 38.20 ± 1.95 cm when treated with microwave electrodeless light (MEL). The chlorophyll content of the plants treated with fluorescent light (FL) was 53.93 ± 1.05 SPAD and was the highest. The antioxidant effect, determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH), was the highest with 92.7 ± 0.2% in plants treated with light-emitting diode (LED)-green light. Total phenol and flavonoid contents were significantly higher with 19.7 ± 0.5 mg GAE/g and 40.2 ± 2.2 mg QE/g in the sample treated with LED-green light, respectively. For antimicrobial activity using the minimum inhibitory concentration (MIC) technique, the inhibitory ability against Escherichia coli was at 0.25 mg/mL under LED-green light treatment. The whitening activity using tyrosinase enzyme showed the highest tyrosinase inhibitory ability at 62.1 ± 1.2% of the above extract treated with MEL light. To confirm the immune activity in lipopolysaccharide (LPS)-induced RAW 264.7 cells, NO production of inflammation-related substances was measured. In addition, the inflammation-related genes iNOS (inducible nitric oxide synthase), COX-2 (cyclooxygenase-2), and TNF-α (tumor necrosis factor-α) in the same sample were confirmed using reverse transcriptase (RT)-PCR, and the result showed that gene expression was suppressed compared with that in the control group. It is expected that Dachul plants treated with LED-blue light will play an important role in enhancing intracellular anti-inflammatory activity. From these results, the effect for various biological activities appeared in a significantly diverse spectrum in response to different wavelengths of artificial light sources in Dachul.

Umbilicaria esculenta Extract Exhibits Antiwrinkle Activity by Suppressing ErbB2 Phosphorylation.

Umbilicaria esculenta (UE), an edible lichen, is widespread in northeast Asian countries, including China, Japan, and Korea. In the present study, we examined the antiwrinkle activity of UE. We observed that the UE extract (UEE) suppressed ultraviolet (UV)-induced matrix metalloprotein-1 (MMP-1) expression and reactive oxygen species (ROS) generation in a human keratinocyte cell line (HaCaT) and human skin tissue. In addition, UEE reversed the UV-induced decrease in collagen in the human skin tissue. Excessive and chronic UV exposure is a key factor underlying skin wrinkle formation via MMP-1 expression. As treatment with UEE disrupted the UV-activated mitogen-activated protein kinase (MAPK) signaling pathway, we applied an antibody array to unveil the underlying mechanism of UEE. Interestingly, UEE treatment inhibited ErbB2 phosphorylation, but not epidermal growth factor receptor phosphorylation, a heterodimerization partner with ErbB2. Furthermore, UEE treatment enhanced UV-suppressed phosphatase activity via ROS suppression. Collectively, our findings indicate that UEE enhances ErbB2 dephosphorylation to suppress UV-induced MMP-1 expression.

Identification of Distinct Subgroups in Moderately Severe Rheumatic Mitral Stenosis Using Data-Driven Phenotyping of Longitudinal Hemodynamic Progression.

Background Rheumatic mitral stenosis is a significant cause of valvular heart disease. Pulmonary arterial systolic pressure (PASP) reflects the hemodynamic consequences of mitral stenosis and is used to determine treatment strategies. However, PASP progression and expected outcomes based on PASP changes in patients with moderately severe mitral stenosis remain unclear. Methods and Results A total of 436 patients with moderately severe rheumatic mitral stenosis (valve area 1.0-1.5 cm2) were enrolled. Composite outcomes included all-cause mortality and hospitalization for heart failure. Data-driven phenotyping identified 2 distinct trajectory groups based on PASP progression: rapid (8.7%) and slow (91.3%). Patients in the rapid progression group were older and had more diabetes and atrial fibrillation than those in the slow progression group (all P<0.05). The initial mean diastolic pressure gradient and PASP were higher in the rapid progression group than in the slow progression group (6.2±2.4 mm Hg versus 5.1±2.0 mm Hg [P=0.001] and 42.3±13.3 mm Hg versus 33.0±9.2 mm Hg [P<0.001], respectively). The rapid progression group had a poorer event-free survival rate than the slow progression group (log-rank P<0.001). Rapid PASP progression was a significant risk factor for composite outcomes even after adjusting for comorbidities (hazard ratio, 3.08 [95% CI, 1.68-5.64]; P<0.001). Multivariate regression analysis revealed that PASP >40 mm Hg was independently associated with allocation to the rapid progression group (odds ratio, 4.95 [95% CI, 2.08-11.99]; P<0.001). Conclusions Rapid PASP progression was associated with a higher risk of the composite outcomes. The main independent predictor for rapid progression group allocation was initial PASP >40 mm Hg.

MsSAMS, a cold stress-responsive gene, provides resistance to environmental stress in T2-generation transgenic plants.

The SAMS (S-adenosylmethionine synthetase) gene is known to play an important role in the mechanism of cold resistance, as overexpression of this gene results in phenotypic changes in T1-generation transgenic plants. Accordingly, this study was conducted to test the expression of the MsSAMS gene in T2-generation transgenic plants and to investigate the resistance of these plants and the function of the transgene in response to various environmental stresses. For the morphological analysis of T2-generation transgenic plants overexpressing the MsSAMS gene, observations using scanning electron microscopy (SEM) were performed. T2-generation transgenic plants were obtained by planting a total of 5 lines, and their characteristics were tested by comparisons with those of the control. SEM revealed that the thickest leaves were produced by the T6 transgenic line-161.24 ± 8.05 µm. The number of stomata ranged from 20.00 ± 2.65 to 34.00 ± 1.00 in the T2-generation transgenic plants, but the control had more stomata. Resistance to various factors, such as low temperature, drought, and oxidative stress, in the T2-generation transgenic plants was also confirmed. Under cold-stress conditions, the T6 transgenic line presented the lowest value (22.73%) of ion leakage, and under drought-stress conditions, compared with the control, the transgenic lines presented lower ion leakage after being treated with various concentrations of mannitol. Even under oxidative-stress conditions, the T2-generation transgenic plants presented ion leakage levels that were 32.91 ± 4.24 to 48.33 ± 3.54% lower than those of the control after treatment with various concentrations of methyl viologen. Regarding SAMS enzyme activity, as the duration of cold treatment increased, the activity in the transgenic plants tended to decrease and then increase. During 48 h of cold treatment, the control showed a decrease in SAM content, while the T2-generation transgenic plants presented an increase in SAM content, from 13.58 ± 1.04 to 22.75 ± 1.95 mg protein/g FW. The results suggest that the MsSAMS gene may be important to the mechanisms of resistance to oxidative and drought stresses in addition to its previously known association with cold resistance. Based on these results, it was suggested that the MsSAMS gene, whose expression is induced by cold stress, can serve as a marker of various responses to environmental stresses, because resistance to cold damage and various environmental stresses are stably inherited in the T2 generation.

The p53-Driven Anticancer Effect of Ribes fasciculatum Extract on AGS Gastric Cancer Cells.

Cancer metastasis is directly related to the survival rate of cancer patients. Although cancer metastasis proceeds by the movement of cancer cells, it is fundamentally caused by its resistance to anoikis, a mechanism of apoptosis caused by the loss of adhesion of cancer cells. Therefore, it was found that inhibiting cancer migration and reducing anoikis resistance are important for cancer suppression, and natural compounds can effectively control it. Among them, Ribes fasciculatum, which has been used as a medicinal plant, was confirmed to have anticancer potential, and experiments were conducted to prove various anticancer effects by extracting Ribes fasciculatum (RFE). Through various experiments, it was observed that RFE induces apoptosis of AGS gastric cancer cells, arrests the cell cycle, induces oxidative stress, and reduces mobility. It was also demonstrated that anoikis resistance was attenuated through the downregulation of proteins, such as epidermal growth factor receptor (EGFR). Moreover, the anticancer effect of RFE depends upon the increase in p53 expression, suggesting that RFE is suitable for the development of p53-targeted anticancer materials. Moreover, through xenotransplantation, it was found that the anticancer effect of RFE confirmed in vitro was continued in vivo.