Regulation of Betaine Homocysteine Methyltransferase by Liver Receptor Homolog-1 in the Methionine Cycle.

Betaine-homocysteine S-methyltransferase (BHMT) is one of the most abundant proteins in the liver and regulates homocysteine metabolism. However, the molecular mechanisms underlying Bhmt transcription have not yet been elucidated. This study aimed to assess the molecular mechanisms underlying Bhmt transcription and the effect of BHMT deficiency on metabolic functions in the liver mediated by liver receptor homolog-1 (LRH-1). During fasting, both Bhmt and Lrh-1 expression increased in the liver of Lrh-1f/f mice; however, Bhmt expression was decreased in LRH-1 liver specific knockout mice. Promoter activity analysis confirmed that LRH-1 binds to a specific site in the Bhmt promoter region. LRH-1 deficiency was associated with elevated production of reactive oxygen species (ROS), lipid peroxidation, and mitochondrial stress in hepatocytes, contributing to hepatic triglyceride (TG) accumulation. In conclusion, this study suggests that the absence of an LRH-1-mediated decrease in Bhmt expression promotes TG accumulation by increasing ROS levels and inducing mitochondrial stress. Therefore, LRH-1 deficiency not only leads to excess ROS production and mitochondrial stress in hepatocytes, but also disrupts the methionine cycle. Understanding these regulatory pathways may pave the way for novel therapeutic interventions against metabolic disorders associated with hepatic lipid accumulation.

Multi-scaled temporal modeling of cardiovascular disease progression: An illustration of proximal arteries in pulmonary hypertension.

The progression of cardiovascular disease is intricately influenced by a complex interplay between physiological pathways, biochemical processes, and physical mechanisms. This study aimed to develop an in-silico physics-based approach to comprehensively model the multifaceted vascular pathophysiological adaptations. This approach focused on capturing the progression of proximal pulmonary arterial hypertension, which is significantly associated with the irreversible degradation of arterial walls and compensatory stress-induced growth and remodeling. This study incorporated critical characteristics related to the distinct time scales for the deformation, thus reflecting the impact of mean pressure on artery growth and tissue damage. The in-silico simulation of the progression of pulmonary hypertension was realized based on computational code combined with the finite element method (FEM) for the simulation of disease progression. The parametric studies further explored the consequences of these irreversible processes. This computational modeling approach may advance our understanding of pulmonary hypertension and its progression.

Loss of SREBP-1c ameliorates iron-induced liver fibrosis by decreasing lipocalin-2.

Sterol regulatory element-binding protein (SREBP)-1c is involved in cellular lipid homeostasis and cholesterol biosynthesis and is highly increased in nonalcoholic steatohepatitis (NASH). However, the molecular mechanism by which SREBP-1c regulates hepatic stellate cells (HSCs) activation in NASH animal models and patients have not been fully elucidated. In this study, we examined the role of SREBP-1c in NASH and the regulation of LCN2 gene expression. Wild-type and SREBP-1c knockout (1cKO) mice were fed a high-fat/high-sucrose diet, treated with carbon tetrachloride (CCl4), and subjected to lipocalin-2 (LCN2) overexpression. The role of LCN2 in NASH progression was assessed using mouse primary hepatocytes, Kupffer cells, and HSCs. LCN2 expression was examined in samples from normal patients and those with NASH. LCN2 gene expression and secretion increased in CCl4-induced liver fibrosis mice model, and SREBP-1c regulated LCN2 gene transcription. Moreover, treatment with holo-LCN2 stimulated intracellular iron accumulation and fibrosis-related gene expression in mouse primary HSCs, but these effects were not observed in 1cKO HSCs, indicating that SREBP-1c-induced LCN2 expression and secretion could stimulate HSCs activation through iron accumulation. Furthermore, LCN2 expression was strongly correlated with inflammation and fibrosis in patients with NASH. Our findings indicate that SREBP-1c regulates Lcn2 gene expression, contributing to diet-induced NASH. Reduced Lcn2 expression in 1cKO mice protects against NASH development. Therefore, the activation of Lcn2 by SREBP-1c establishes a new connection between iron and lipid metabolism, affecting inflammation and HSCs activation. These findings may lead to new therapeutic strategies for NASH.

A Facile Method to Fabricate an Enclosed Paper-Based Analytical Device via Double-Sided Patterning for Ionic Contaminant Detection.

Microfluidic paper-based analytical devices (µPADs) have been developed for use in a variety of diagnosis and analysis fields. However, conventional µPADs with an open-channel system have limitations for application as analytical platforms mainly because of the evaporation and contamination of the sample solution. This study demonstrates the design and fabrication of an enclosed three-dimensional(3D)-µPAD and its application as a primary early analysis platform for ionic contaminants. To generate the hydrophobic PDMS barrier, double-sided patterning is carried out using a PDMS blade-coated stamp mold that is fabricated using 3D printing. The selective PDMS patterning can be achieved with controlled PDMS permeation of the cellulose substrate using 3D-designed stamp molds. We find the optimal conditions enabling the formation of enclosed channels, including round shape pattern and inter-pattern distance of 10 mm of stamp design, contact time of 0.5 min, and spacer height of 300 µm of double-sided patterning procedure. As a proof of concept, this enclosed 3D-µPAD is used for the simultaneous colorimetric detection of heavy metal ions in a concentration range of 0.1-2000 ppm, including nickel (Ni2+), copper (Cu2+), mercury (Hg2+), and radioactive isotope cesium-137 ions (Cs+). We confirm that qualitative analysis and image-based quantitative analysis with high reliability are possible through rapid color changes within 3 min. The limits of detection (LOD) for 0.55 ppm of Ni2+, 5.05 ppm of Cu2+, 0.188 ppm of Hg2+, and 0.016 ppm of Cs+ are observed, respectively. In addition, we confirm that the analysis is highly reliable in a wide range of ion concentrations with CV values below 3% for Ni2+ (0.56%), Cu2+ (0.45%), Hg2+ (1.35%), and Cs+ (2.18%). This method could be a promising technique to develop a 3D-µPAD with various applications as a primary early analysis device in the environmental and biological industries.

Effects of intraoperative inspired oxygen fraction (FiO2 0.3 vs 0.8) on patients undergoing off-pump coronary artery bypass grafting: the CARROT multicenter, cluster-randomized trial.

BACKGROUND: To maintain adequate oxygenation is of utmost importance in intraoperative care. However, clinical evidence supporting specific oxygen levels in distinct surgical settings is lacking. This study aimed to compare the effects of 30% and 80% oxygen in off-pump coronary artery bypass grafting (OPCAB). METHODS: This multicenter trial was conducted in three tertiary hospitals from August 2019 to August 2021. Patients undergoing OPCAB were cluster-randomized to receive either 30% or 80% oxygen intraoperatively, based on the month when the surgery was performed. The primary endpoint was the length of hospital stay. Intraoperative hemodynamic data were also compared. RESULTS: A total of 414 patients were cluster-randomized. Length of hospital stay was not different in the 30% oxygen group compared to the 80% oxygen group (median, 7.0 days vs 7.0 days; the sub-distribution hazard ratio, 0.98; 95% confidence interval [CI] 0.83-1.16; P = 0.808). The incidence of postoperative acute kidney injury was significantly higher in the 30% oxygen group than in the 80% oxygen group (30.7% vs 19.4%; odds ratio, 1.94; 95% CI 1.18-3.17; P = 0.036). Intraoperative time-weighted average mixed venous oxygen saturation was significantly higher in the 80% oxygen group (74% vs 64%; P < 0.001). The 80% oxygen group also had a significantly greater intraoperative time-weighted average cerebral regional oxygen saturation than the 30% oxygen group (56% vs 52%; P = 0.002). CONCLUSIONS: In patients undergoing OPCAB, intraoperative administration of 80% oxygen did not decrease the length of hospital stay, compared to 30% oxygen, but may reduce postoperative acute kidney injury. Moreover, compared to 30% oxygen, intraoperative use of 80% oxygen improved oxygen delivery in patients undergoing OPCAB. Trial registration ClinicalTrials.gov (NCT03945565; April 8, 2019).

An ensemble machine learning approach to predict postoperative mortality in older patients undergoing emergency surgery.

BACKGROUND: Prediction of preoperative frailty risk in the emergency setting is a challenging issue because preoperative evaluation cannot be done sufficiently. In a previous study, the preoperative frailty risk prediction model used only diagnostic and operation codes for emergency surgery and found poor predictive performance. This study developed a preoperative frailty prediction model using machine learning techniques that can be used in various clinical settings with improved predictive performance. METHODS: This is a national cohort study including 22,448 patients who were older than 75 years and visited the hospital for emergency surgery from the cohort of older patients among the retrieved sample from the Korean National Health Insurance Service. The diagnostic and operation codes were one-hot encoded and entered into the predictive model using the extreme gradient boosting (XGBoost) as a machine learning technique. The predictive performance of the model for postoperative 90-day mortality was compared with those of previous frailty evaluation tools such as Operation Frailty Risk Score (OFRS) and Hospital Frailty Risk Score (HFRS) using the receiver operating characteristic curve analysis. RESULTS: The predictive performance of the XGBoost, OFRS, and HFRS for postoperative 90-day mortality was 0.840, 0.607, and 0.588 on a c-statistics basis, respectively. CONCLUSIONS: Using machine learning techniques, XGBoost to predict postoperative 90-day mortality, using diagnostic and operation codes, the prediction performance was improved significantly over the previous risk assessment models such as OFRS and HFRS.

Phenolic from apple blossom "Hongro" inhibits the expression of proteins related to melanogenesis in B16F10 melanoma cells.

This study aimed to assess apple blossom extracts as potential natural whitening agents due to their ability to inhibit melanogenesis. Ethanol extracts of apple blossom (ABE) were assessed for biological activity in the B16F10 mouse melanoma cell line. ABE toxicity was assessed by thiazolyl blue tetrazolium bromide (MTT) assay. Levels of melanogenic enzyme expression in response to ABE supplementation were assessed by western blotting. Also assessed purified kaempferol, one of the phenolic compounds extracted from apple blossom, was evaluated using western blot analysis. The expression levels of cellular tyrosinase, microphthalmia-associated transcription factor (MITF), tyrosinase-related protein (TRP)-1, and TRP-2 proteins related to melanogenesis decreased in a dose-dependent manner with ABE treatment of cells. Using nuclear magnetic resonance, we identified kaempferol in the ABE. Treatment of cells with purified kaempferol decreased the expression levels of tyrosinase and the MITF protein to a similar degree as that observed with ABE treatment. This suggests that the efficacy of melanogenesis-related inhibition demonstrated by ABE was due to kaempferol. ABE has an inhibitive effect on melanogenic enzymes and potentially can be applied to functional foods and cosmetics having a whitening effect as a natural material.

SCAP deficiency facilitates obesity and insulin resistance through shifting adipose tissue macrophage polarization.

INTRODUCTION: Sterol regulatory element binding protein (SREBP) cleavage-associating protein (SCAP) is a sterol-regulated escort protein that translocates SREBPs from the endoplasmic reticulum to the Golgi apparatus, thereby activating lipid metabolism and cholesterol synthesis. Although SCAP regulates lipid metabolism in metabolic tissues, such as the liver and muscle, the effect of macrophage-specific SCAP deficiency in adipose tissue macrophages (ATMs) of patients with metabolic diseases is not completely understood. OBJECTIVES: Here, we examined the function of SCAP in high-fat/high-sucrose diet (HFHS)-fed mice and investigated its role in the polarization of classical activated macrophages in adipose tissue. METHODS: Macrophage-specific SCAP knockout (mKO) mice were generated through crossbreeding lysozyme 2-cre mice with SCAP floxed mice which were then fed HFHS for 12 weeks. Primary macrophages were derived from bone marrow cells and analyzed further. RESULTS: We found that fat accumulation and the appearance of proinflammatory M1 macrophages were both higher in HFHS-fed SCAP mKO mice relative to floxed control mice. We traced the effect to a defect in the lipopolysaccharide-mediated increase in SREBP-1a that occurs in control but not SCAP mKO mice. Mechanistically, SREBP-1a increased expression of cholesterol 25-hydroxylase transcription, resulting in an increase in the production of 25-hydroxycholesterol (25-HC), an endogenous agonist of liver X receptor alpha (LXRα) which increased expression of cholesterol efflux to limit cholesterol accumulation and M1 polarization. In the absence of SCAP mediated activation of SREBP-1a, increased M1 macrophage polarization resulted in reduced cholesterol efflux downstream from 25-HC-dependent LXRα activation. CONCLUSION: Overall, the activation of the SCAP-SREBP-1a pathway in macrophages may provide a novel therapeutic strategy that ameliorates obesity by controlling cholesterol homeostasis in ATMs.

Impact of Body Mass Index and Sarcopenia on Short- and Long-Term Outcomes After Esophageal Cancer Surgery: An Observational Study.

BACKGROUND: The effects of specific body mass index (BMI) category and sarcopenia within each BMI category on outcomes in patients undergoing esophageal surgery with esophageal squamous cell carcinoma have not been thoroughly examined. METHODS: This study included 1141 patients. Sarcopenia was determined with a total psoas muscle cross-sectional area at the level of the third lumbar vertebra in computed tomography. The outcomes were long-term survival, including overall survival (OS) and recurrence-free survival (RFS), and postoperative complications. RESULTS: The overweight and no sarcopenia group was considered as the reference. After adjusting covariates, the underweight and the normal weight and sarcopenia groups both showed worse OS (underweight group: hazard ratio [HR] 2.04, 95% confidence interval [CI] 1.33-3.13, p = 0.001; normal weight and sarcopenia group: HR 1.93, 95% CI 1.39-2.69, p < 0.001) and worse RFS (underweight group: HR 1.78, 95% CI 1.19-2.67, p = 0.005; normal weight and sarcopenia group: HR 1.70, 95% CI 1.25-2.30, p = 0.001). In addition, the underweight group (odds ratio [OR] 4.74, 95% CI 2.05-10.96, p < 0.001), the normal weight and sarcopenia group (OR 3.26, 95% CI 1.60-6.62, p = 0.001), the overweight and sarcopenia group (OR 2.54, 95% CI 1.14-5.68, p = 0.023), and the obese and no sarcopenia group (OR 2.44, 95% CI 1.14-5.22, p = 0.021) were at significantly higher risk of postoperative 30-day composite complications. CONCLUSIONS: Compared with the overweight and no sarcopenia group, the underweight and the normal weight and sarcopenia groups were associated with worse short- and long-term outcomes.

Isoquercitrin isolated from newly bred Green ball apple peel in lipopolysaccharide-stimulated macrophage regulates NF-κB inflammatory pathways and cytokines.

Apple peel has several bioactive properties. The fruit is grown worldwide, and its ingredients are used medicinally. However, its anti-inflammatory activities are poorly characterized. In this study, isoquercitrin isolated from newly bred Green ball apple peel from Korea showed anti-inflammatory effects. To confirm its anti-inflammatory effects, isoquercitrin was treated with lipopolysaccharide, which induces proinflammatory factors in Raw 264.7 macrophage cells. Proinflammatory effects were measured by real-time polymerase chain reaction and Western blotting as well as enzyme-linked immunosorbent assay. Cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay to define the isoquercitrin concentration nontoxic to cells. Nitric oxide (NO) production, prostaglandin E2, inducible NO synthase, cyclooxygenase-2 (COX-2), and nuclear factor-κB p65 protein expression decreased in a concentration-dependent manner by isoquercitrin. mRNA expression of tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, monocyte chemoattractant protein-1, and prostaglandin E synthase 2 (PTGES2) as proinflammatory factors significantly decreased. PTGES2, which was stimulated by COX-2 and involved in PGE2 expression, was inhibited. Therefore, this study rendered isoquercitrin isolated from the newly bred Green ball apple peel as a potential pharmacological alternative to treat inflammation-related diseases.

Reliability and Validity of the Korean Version of Children's Depression Inventory 2 Short Version as a Screening Tool: A Comparison With the Standard 28-Item Version.

OBJECTIVE: To investigate the reliability and validity of the Korean version of Children's Depression Inventory 2 Short Version (CDI 2:S) in comparison with its full-length version (CDI 2) as a screening tool for depressive youth. METHODS: A total of 714 children from the community and 62 psychiatric patients were enrolled in this study. The Korean version of the Kiddie Schedule for Affective Disorders and Schizophrenia Present and Lifetime Version (K-SADS-PL-K) served as the reference standard for computing receiver operating characteristic (ROC) curves. To evaluate the ability of the CDI 2 and CDI 2:S to discriminate major depressive disorders, areas under the curves (AUCs) were compared. To investigate psychometric properties of the CDI 2:S, internal consistency was calculated and confirmatory factor analysis was conducted. RESULTS: For the CDI 2, the cutoff at 20 yielded the best balance between sensitivity (83%) and specificity (91%). For the CDI 2:S, the cutoff point of 10 resulted in high sensitivity (82%) and high specificity (93%). The short form was proven to be as sensitive and specific as the CDI 2. Further analyses confirmed that the CDI 2:S also had good reliability and validity. CONCLUSION: The CDI 2:S, a sensitive and brief form of the CDI 2, may serve as a better option in time-constrained psychiatric settings.

Comparison of Preoperative Nutritional Indexes for Outcomes after Primary Esophageal Surgery for Esophageal Squamous Cell Carcinoma.

BACKGROUND: This study aimed to compare the controlling nutritional status (CONUT) score, prognostic nutritional index (PNI), and geriatric nutritional risk index (GNRI) for predicting postoperative outcomes in patients with esophageal squamous cell carcinoma undergoing esophagectomy. METHODS: We retrospectively reviewed the data of 1265 consecutive patients who underwent elective esophageal surgery. The patients were classified into no risk, low-risk, moderate-risk, and high-risk groups based on nutritional scores. RESULTS: The moderate-risk (hazard ratio [HR]: 1.55, 95% confidence interval [CI]: 1.24-1.92, p < 0.001 in CONUT; HR: 1.61, 95% CI: 1.22-2.12, p = 0.001 in GNRI; HR: 1.65, 95% CI: 1.20-2.26, p = 0.002 in PNI) and high-risk groups (HR: 1.91, 95% CI: 1.47-2.48, p < 0.001 in CONUT; HR: 2.54, 95% CI: 1.64-3.93, p < 0.001 in GNRI; HR: 2.32, 95% CI: 1.77-3.06, p < 0.001 in PNI) exhibited significantly worse 5-year overall survival (OS) compared with the no-risk group. As the nutritional status worsened, the trend in the OS rates decreased (p for trend in all indexes < 0.05). CONCLUSIONS: Malnutrition, evaluated by any of three nutritional indexes, was an independent prognostic factor for postoperative survival.

Predictive Model for the Assessment of Preoperative Frailty Risk in the Elderly.

Adequate preoperative evaluation of frailty can greatly assist in the efficient allocation of hospital resources and planning treatments. However, most of the previous frailty evaluation methods, which are complicated, time-consuming, and can have inter-evaluator error, are difficult to apply in urgent situations. Thus, the authors aimed to develop and validate a predictive model for pre-operative frailty risk of elderly patients by using diagnostic and operation codes, which can be obtained easily and quickly from electronic records. We extracted the development cohort of 1762 people who were hospitalized for emergency operations at a single institution between 1 January 2012 and 31 December 2016. The temporal validation cohort from 1 January 2017 to 31 December 2018 in the same center was set. External validation was conducted on 6432 patients aged 75 years or older from 2012 to 2015 who had emergency surgery in the Korean national health insurance database. We developed the Operation Frailty Risk Score (OFRS) by assessing the association of Operation Group and Hospital Frailty Risk Score with the 90-day mortality through logistic regression analysis. We validated the OFRS in both the temporal validation cohort and two external validation cohorts. In the temporal validation cohort and the external validation cohort I and II, the c-statistics for OFRS to predict 90-day mortality were 0.728, 0.626, and 0.619, respectively. OFRS from these diagnostic codes and operation codes may help evaluate the peri-operative frailty risk before emergency surgery for elderly patients where history-taking and pre-operative testing cannot be performed.

Postoperative changes in left ventricular systolic function after combined mitral and aortic valve replacement in patients with rheumatic heart disease.

BACKGROUNDS: We sought to identify short- and long-term changes in postoperative left ventricular systolic function in patients with rheumatic heart disease (RHD) who underwent combined aortic and mitral valve replacement. METHODS: We analyzed 146 patients according to their preoperative left ventricular ejection fraction (LVEF) (113 with preoperative LVEF ≥50% and 33 with preoperative LVEF <50%). A restricted cubic spline model was used to assess the effect of time on the postoperative changes in echocardiographic parameters. RESULTS: There were no significant difference in preoperative and immediately postoperative LVEF before discharge in either group. During median follow-up of 3.2 years (interquartile range: 1.3-4.7 years) after surgery, postoperative LVEF increased slightly and then plateaued in patients with preoperative LVEF ≥50%, whereas it increased over 3-4 years after surgery and then gradually decreased in patients with preoperative LVEF <50% (p < .001). CONCLUSION: Long-term postoperative LVEF showed a downward trend in RHD patients with reduced preoperative LVEF, whereas it reached a plateau in RHD patients with normal preoperative LVEF.

Plasticity and Enzymatic Degradation Coupled With Volumetric Growth in Pulmonary Hypertension Progression.

Pulmonary hypertension (PH) is one of the least understood and highly elusive cardiovascular conditions associated with elevated pulmonary arterial pressure. Although the disease mechanisms are not completely understood, evidence has accumulated from human and animal studies that irreversible processes of pulmonary arterial wall damage, compensated by stress-mediated growth, play critical roles in eliciting the mechanisms of disease progression. The aim of this study is to develop a thermodynamic modeling structure of the pulmonary artery to consider coupled plastic-degradation-growth irreversible processes to investigate the mechanical roles of the dissipative phenomena in the disease progression. The proposed model performs a model parameter study of plastic deformation and degradation processes coupled with dissipative growth subjected to elevated pulmonary arterial pressure and computationally generates in silico simulations of PH progression using the clinical features of PH, found in human morphological and mechanical data. The results show that considering plastic deformation can provide a much better fitting of the ex vivo inflation tests than a widely used pure hyperelastic model in higher pressure conditions. In addition, the parameter sensitivity study illustrates that arterial damage and growth cause the increased stiffness, and the full simulation (combining elastic-plastic-degradation-growth models) reveals a key postpathological recovery process of compensating vessel damage by vascular adaptation by reducing the rate of vessel dilation and mediating vascular wall stress. Finally, the simulation results of luminal enlargement, arterial thickening, and arterial stiffness for an anisotropic growth are found to be close to the values from the literature.

Molecular Weight Distribution of Two Types of Living Chains Formed during Nitroxide-Mediated Polymerization of Styrene.

Different types of polymer chains generated during the nitroxide-mediated polymerization of styrene are separated for the first time, and their molecular weight distribution (MWD) is investigated. Living and dead chains are monitored during the reaction; specifically, two types of living chains derived from the initiation of the alkoxyamine (RT) and the self-initiation of styrene and dead chains present in the as-prepared polystyrene (PS). To distinguish between each polymer species, different numbers of hydroxyl groups are introduced onto the T and R groups of the alkoxyamine (one and two groups, respectively). Each living and dead chains is resolved according to the distinct number of hydroxyl groups on its chain-end using high-performance liquid chromatography. Molecular structures of the fractionated PS are characterized using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and 1 H nuclear magnetic resonance spectroscopy, and the results of which show two distinct initiation paths: one originating from RT and the other from the self-initiation of styrene. Molecular weight and MWD are measured using size-exclusion chromatography and reveal a narrow MWD for the living chains derived from RT. Contrastingly, a broad and skewed MWD is observed for the other living chains derived from the self-initiation of styrene and the dead chains.

Isolated isoquercitrin from Green ball apple peel inhibits photoaging in CCD-986Sk fibroblasts cells via modulation of the MMPs signaling.

BACKGROUND: Ultraviolet B (UVB) irradiation is viewed as the main factor of skin aging, associated with acceleration of elastin, collagen degradation and expression of matrix metalloproteinases (MMPs). Apples are one of the most commonly eaten fruits in the world, and isoquercitrin is the main active ingredient in new bred varieties "Green ball" apple. Therefore, we are studying the functionality of the active ingredient of apple, a natural raw material that does not have toxicity or sensitivity problems. OBJECTIVES: The aim of this study, we scrutinized the effects of isoquercitrin on skin photoaging in UVB-exposed human fibroblasts (CCD-986Sk). METHODS: To investigate the inhibition effect on photoaging factor regulation, isolated isoquercitrin were treated with UVB, which induces photoaging-related factors in CCD-986Sk fibroblast cells. Pro-inflammatory factors were measured by ELISA, Western blotting and real-time PCR. RESULTS: Isoquercitrin exhibited antioxidant activity and UVB-induced generation of photoaging-related factor inhibition without showing any toxicity. Anti-photoaging effect for protein levels using Isoquercitin was competent, of both the combate MMP-1 and MMP-9. Also, effect of COL1A2 product significantly increase, from up regulating the TIMP-1 mediated pathway in CCD-986Sk cells via the inhibition of MMPs. Isoquercitrin also downregulated the mRNA gene expression of MMPs while upregulating type I procollagen, HAS2 by modulating TIMP-1 and TGF-ß in UVB-irradiated CCD-986Sk cells. CONCLUSIONS: Collectively, our results show that isoquercitrin might be useful as a functional food while being a good candidate in the development of cosmetic products and medicines for the remedy of UVB-induced skin photoaging.

Identification of Pre-Diabetic Biomarkers in the Progression of Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is a major global health issue. The development of T2DM is gradual and preceded by the pre-diabetes mellitus (pre-DM) stage, which often remains undiagnosed. This study aimed to identify novel pre-DM biomarkers in a high-fat diet (HFD)-induced pre-DM mouse model. Male C57BL/6J mice were fed either a chow diet or HFD for 12 weeks. Serum and liver samples were isolated in a time-dependent manner. Semi-quantitative assessment of secretory cytokines was performed by cytokine array analysis, and 13 cytokines were selected for further analysis based on the changes in expression levels in the pre-DM and T2DM stages. HFD-fed mice gained body weight and exhibited high serum lipid, liver enzyme, glucose, and insulin levels during the progression of pre-DM to T2DM. The mRNA expression of inflammatory and lipogenic genes was elevated in HFD-fed mice The mRNA expression of Fc receptor, IgG, low affinity Iib, lectin, galactose binding, soluble 1, vascular cell adhesion molecule 1, insulin-like growth factor binding protein 5, and growth arrest specific 6 was elevated in the pre-DM, which was confirmed by measuring protein levels. Our study identified novel pre-DM biomarkers that may help to delay or prevent the progression of T2DM.