Abstract Background: Early identification of patients at risk of AKI after cardiac surgery is of critical importance for optimizing perioperative management and improving outcomes. This study aimed to identify the association between preoperative myoglobin levels and postoperative acute kidney injury (AKI) in patients undergoing valve surgery or coronary artery bypass graft surgery (CABG) with cardiopulmonary bypass. Methods: This retrospective study included 293 patients aged over 17 years who underwent valve surgery or CABG with cardiopulmonary bypass. We excluded 87 patients as they met the exclusion criteria. Therefore, 206 patients were included in the final analysis. The patients’ demographics as well as intraoperative and postoperative data were collected from electronic medical records. AKI was defined according to the Acute Kidney Injury Network classification system. Results: Of the 206 patients included in this study, 77 developed AKI. The patients who developed AKI were older, had a history of hypertension, underwent valve surgery with concomitant CABG, had lower preoperative hemoglobin levels, and experienced prolonged extracorporeal circulation (ECC) times. Multivariate logistic regression analysis revealed that preoperative myoglobin levels and ECC time were correlated with the development of AKI. A higher preoperative myoglobin level was an independent risk factor for the development of cardiac surgery-associated AKI. Conclusions: Higher preoperative myoglobin levels may enable physicians to identify patients at risk of developing AKI and optimize management accordingly.

Abstract Introduction Contact granulomas (CGs) and intubation granulomas (IGs) are known to have different clinical manifestations despite having the same pathological features. Objectives The purpose of the present study was to analyze the treatment results for CG and IG and to obtain clinical information. Methods We retrospectively reviewed the medical records of patients diagnosed with vocal process granuloma (VPG) between January 2015 and December 2018. The patient’s age, sex, medical history, lesion size, lesion type, reflux finding score (RFS), response to treatment, duration of treatment, and follow-up period were compared. Results Eighteen patients with CG and 14 patients with IG were included in the study. The IG group had more female patients (p = 0.0009), showed better response to proton pump inhibitor (PPI) and steroid inhalation (SI) (p = 0.036), and had a shorter treatment period (p = 0.0029) than the CG group. Five patients who received botulinum toxin injections in their vocal cords had complete remission. Conclusions Compared with CG, IG was more responsive to treatment with PPI and SI and required a shorter duration of treatment.

Abstract The aim of this study was to investigate the anticancer effect of Oenanthe stolonifera D.C extract (OJE) on Hep3B, a human liver cancer cell, and identify the anticancer mechanisms. When treated with 1.0 mg/mL of OJE in HEK-293 and HEP3B to test the anticancer effect based on cell viability and mobility, the extract showed no growth inhibitory effect on HEK-293, while Hep3B's cell viability and mobility significantly decreased to 62.5% and 48.6%, respectively. The RNA expression levels of AMP-activated protein kinase (AMPK), protein-53 (p53), and cyclooxygenase-2 (COX-2), which are key genes of carcinogenesis, were examined to investigate the mechanism of the anticancer effect. OJE downregulated COX-2 and increased the expression of cancer suppressors AMPK and p53 in a concentration-dependent manner. HPLC analysis was conducted to quantify secondary metabolites in OJE, and 0.50 mg/g DM of chlorogenic acid was identified as the main substance. Therefore, Oenanthe stolonifera D.C containing bioactive substances is valuable as a natural source for anticancer agent in the food and pharmaceutical industries.

Abstract Cell apoptosis induction and metastasis suppression in human breast cancer cell, MDA-MB-231, were studied to assess the potential of Cirsium setidens extract (CSE) on breast cancer treatment. Cell viability and metastasis analysis using MDA-MB-231 confirmed CSE significantly inhibited the growth and proliferation of cancer cell without suppressing normal cell growth in the range of 0.25 to 0.5 mg/mL of CSE. To analyze the anticancer effect of CSE, the expressions of major genes related to in the apoptosis, including p53, AMPK-α, Bcl-2, and Bax were analyzed by reverse transcription-polymerase chain reaction. The expressions of AMPK-α, p53, and Bax increased by 45, 43, and 68%, respectively, while the expression of Bcl-2 decreased by 12%, showing that CSE treatment induced apoptosis of MDA-MB-231. The major compound of CSE was identified as rhoifolin, a type of flavone, through analysis using LC-MS/MS. Our findings confirmed that rhoifolin, known to possess a variety of significant biological activities, could be obtained from C. setidens and used as an effective natural compound to suppress breast cancer.

Abstract The purpose of this study is to investigate the effect of bioconverted Oenanthe javanica extract (BOE) using Lactiplantibacillus plantarum SM4 on production of bioactive compounds. Response surface methodology was used to determine the optimal ultrasound-assisted extraction conditions including the extraction time, extraction temperature, and ethanol concentration for the enhancement of bioactive compounds production. The predicted optimum UAE conditions were extraction time of 26.0 min, extraction temperature of 92.8 °C, and 59.9% ethanol, respectively, and 5.14 mg GAE/g DM of TPC and 0.59 mg QE/g DM of TFC were produced under the optimum condition. Then, O. javanica extraction (OJE) has been bioconverted by using L. plantarum SM4 to increase the bioactive compounds. In HPLC-mass spectrometry analyses, higher concentration of p-coumaric acid was identified in BOE than in OJE, and chlorogenic acid in OJE was converted to quinic acid, confirming an increase in bioactive compounds by bioconversion. Thus, we have concluded that optimization of UAE and the BOE is an effective process for enhancement bioactive compounds from O. Javanica and this finding provides a scientific basis of bioactive compounds in natural product can be utilized as food, cosmetics, and pharmaceutical materials from BOE.

Abstract Although cryopreservation is an efficient method for maintaining the biological and genetic resources of sperm, the sperm damage during the cryopreservation process cannot be ignored. It should be possible to obtain the most effective cryopreservation performance by accurately grasping the effects of various factors on the cryopreservation of sperm. The previous study demonstrated that a suitable standard protocol for cryopreservation of Korean native brindled cattle (Chikso) does not exist, based on the methods for semen cryopreservation of Chikso differ in each research center. The most obvious difference between most of protocols is the addition of glycerol before and after cooling during the Chikso cryopreserved semen process. Therefore we focused on the effects of glycerol addition time on the quality of cryopreserved Chikso sperm. In the present study, 27 individual Chikso samples were collected by transrectal massage and divided into two parts: the “cryopreservation method A” group (adding glycerol before cooling) and the “cryopreservation method B” group (adding glycerol after cooling). Meanwhile, the values of various sperm parameters were derived from each group, including sperm motility, kinematics, capacitation status, cell viability, and intracellular ATP levels, which we used to compare and evaluate sperm function. The results of this study indicated that during the semen cryopreservation process of the Chikso, the addition of glycerol after cooling yielded superior results in a variety of sperm parameters, such as sperm motility, progressive motility, rapid motility, VCL, VSL, VAP, ALH, capacitation status, viability, and intracellular ATP level after freezing and thawing. Our study is suggested that the glycerol addition time during the cryopreservation process for Chikso should be considered. In addition, our results may be provided reference to develop suitable the cryopreservation procedure of the Chikso sperm.

ABSTRACT Background : Albuminuria predicts progression of diabetic nephropathy (DN) but lacks specificity and sensitivity for the diagnosis of chronic kidney disease (CKD) and progressive decline in estimated glomerular filtration rate (eGFR). We evaluated the decline in renal function in patients with DN and analyzed the prognosis of renal function according to the level of albuminuria and the incidence of cardiovascular disease (CVD), cerebrovascular diseases, and peripheral artery disease (PAD) according to the level of albuminuria. Methods: This retrospective study included 331 patients with eGFR >60 mL/min/1.73 m2 and urinary albumin/creatinine (Cr) ratio (ACR) >30 mg/g Cr who were treated at the Chungnam National University Hospital between January 2012 and December 2018. Patients were divided into mildly increased albuminuria, moderately increased albuminuria, and severely increased albuminuria groups according to their urine ACRs of 30-300, 300 900, and >900 mg/g Cr, respectively. Renal outcomes and incidence of CVD, cerebrovascular disease, and PAD were compared among the three groups. Results: More severe albuminuria was associated with higher rates of progression to CKD (p< 0.001) and >50% reduction in eGFR from baseline (p< 0.001). There was a statistically significant difference in the rate of PCI with angina or myocardial infarction (p=0.030). However, cerebrovascular disease and PAD did not significantly differ among the three groups. Conclusión: Among patients with DN who maintained a relatively preserved renal function with an eGFR >60 mL/min/1.73 m2, the rates of renal deterioration and progression to CKD were significantly more frequent in those with more severe albuminuria.

RESUMEN Antecedentes: La albuminuria predice la progresión de la nefropatía diabética (ND) pero carece de especificidad y sensibilidad para el diagnóstico de la enfermedad renal crónica (ERC) y la disminución progresiva en la tasa de filtración glomerular estimada (eGFR). Evaluamos la disminución de la función renal en pacientes con ND y analizamos el pronóstico de la función renal de acuerdo con el nivel de albuminuria y la incidencia de enfermedad cardiovascular (ECV), enfermedades cerebrovasculares y enfermedad de las arterias periféricas (EAP) de acuerdo con el nivel de albuminuria. Material y métodos: Este estudio retrospectivo incluyó a 331 pacientes con eGFR >60 ml/min/1,73 m2 y de albúmina urinaria/creatinina (CR) (ACR) >30 mg/g CR que fueron tratados en el Hospital Universitario Nacional de Chungnam entre enero de 2012 y diciembre de 2018. Los pacientes se dividieron en tres grupos: albuminuria ligeramente aumentada, aumento moderado de albuminuria y aumento severo de albuminuria de acuerdo con sus ACRs de orina de 30-300, 300-900 y >900 mg/g Cr, respectivamente. Los resultados renales e incidencia de ECV, enfermedad cerebrovascular y EAP se compararon entre los tres grupos. Resultados: La albuminuria más severa se asoció con tasas más altas de progresión a ERC (P <0,001) y una reducción >50% en eGFR desde la línea de base (P <0,001). Hubo una diferencia estadísticamente significativa en la tasa de PCI con la angina o el infarto de miocardio (P =0,030). Sin embargo, la enfermedad cerebrovascular y la EAP no difirieron significativamente entre los tres grupos. Conclusión: entre los pacientes con ND que mantuvieron una función renal relativamente conservada con un eGFR >60 ml/ min/1,73 m2, las tasas de deterioro renal y la progresión a la ERC fueron significativamente más frecuentes en aquellos con albuminuria más severa.

ABSTRACT The anecdotal report describes two examples of COVID-19-positive healthcare professionals (HCPs) who had worked as nurses during pre-symptomatic period and subsequently presented a mild clinical course of COVID-19. The nurses’ responsibilities were almost the same and worked in the general ward with no aerosol generating medical procedures. Two HCPs were expected to have similar infectiousness, but the number of secondary transmission by each HCP were different. Eleven close contacts from HCP1 were notified, and all of them tested negative for SARS-CoV-2. However, 13 of 35 close contacts of HCP2 tested positive for SARS-CoV-2. While working, mask-wearing style differed between the two HCPs. HCP1 wore a KF94 mask appropriately and kept wearing it while working.HCP2 wore a surgical mask while working, but often pulled it down to her chin or removed it. It was strongly suspected that the difference of mask wearing contributed to the SARS-CoV-2 transmission. However, other factors such as talkative behavior, exposure time, ventilation in rooms, and hand hygiene performance rates, could also have affected the transmission of COVID-19.It is crucial that healthcare workers wear a mask adequately and continuously, and they maintain proper hand hygiene while working during the COVID-19 pandemic.

ABSTRACT Purpose To investigate the role of Nrf2/HO-1 in renal histopathological ailments time-dependently in asphyxial cardiac arrest (CA) rat model. Methods Eighty-eight Sprague Dawley male rats were divided into five groups of eight rats each. Asphyxial CA was induced in all the experimental rats except for the sham group. The rats were sacrificed at 6 hours, 12 hours, one day and two days post-CA. Serum blood urea nitrogen (BUN), creatinine (Crtn) and malondialdehyde from the renal tissues were evaluated. Hematoxylin and eosin and periodic acid-Schiff staining were done to evaluate the renal histopathological changes in the renal cortex. Furthermore, Nrf2/HO-1 immunohistochemistry (ihc) and western blot analysis were performed after CA. Results The survival rate of rats decreased in a time-dependent manner: 66.6% at 6 hours, 50% at 12 hours, 38.1% in one day, and 25.8% in two days. BUN and serum Crtn markedly increased in CA-operated groups. Histopathological ailments of the renal cortical tissues increased significantly from 6 hours until two days post-CA. Furthermore, Nrf2/HO-1 expression level significantly increased at 6 hours, 12 hours, and one day. Conclusions The survival rate decreased time-dependently, and Nrf/HO-1 expression increased from 6 hours with the peak times at 12 hours, and one day post-CA.

Abstract Bovine embryonic development is closely associated with mitochondrial biogenesis, which is regulated by the sirtuin 1 (SIRT1). Resveratrol, which is a type of natural phenol produced by several plants and used as a dietary supplement, is the activator of SIRT1. Although it has been reported that resveratrol increased SIRT1 level in in vitro bovine blastocysts, there are no in vivo reports on the change in the plasma SIRT1 level in cows. Therefore, we investigated the change in the level of plasma SIRT1 by injecting different concentrations of resveratrol into the uterus of Korean cattle heifer. The level of plasma SIRT1 in the 1.0 μM resveratrol-injected group was the highest among all groups (P < 0.05). Although the level of plasma SIRT1 increased on days 7, 9, and 14 in the resveratrol-injected group, the level of plasma SIRT1 in the control group decreased. When 1.0 µM resveratrol was directly injected into the uterus of cows during artificial insemination, a pregnancy rate was 21.0% higher than that in the control group. In conclusion, our results identified that the level of plasma SIRT1 was increased by direct injection of resveratrol and improved conception rate by injection into uterus of cow during artificial insemination.

Abstract BRCA1-associated protein 1 (BAP1) is a deubiquitinating enzyme that has long been considered to be a tumor suppressor in various tumors, including renal cell carcinoma, uveal melanoma, mesothelioma, and cutaneous melanoma. However, the involvement of BAP1 in the progression of prostate cancer has not been studied until recently. Herein, we investigated the tumor promoting function of BAP1 in the context of prostate cancer. Analysis of The Cancer Genome Atlas (TCGA) data set showed that prostate cancer patients express high levels of BAP1 mRNA. High BAP1 expression is inversely correlated with disease-free survival in patients with prostate cancer. Among the prostate cell lines tested, BAP1 expression was high in tumorigenic and metastatic cell lines, but was low in normal prostate cell line. Knockdown of BAP1 in PC3 or DU145 cells induced mesenchymal-to-epithelial transition (MET). Further, BAP1-knockdown resulted in decreased migration and invasion of PC3 and DU145 cells. Conversely, overexpression of BAP1 in RWPE1, a normal prostate cell line, induced the migratory and invasive properties. Collectively, our findings identified that BAP1 has a tumor promoting function in prostate cancer cells, and suggest that BAP1 can serve as a potential therapeutic target for prostate cancer.

Abstract Regulation of target proteins by the ubiquitin-proteasome system (UPS) is common in a wide range of cellular events, including transcriptional regulation, cell cycle progression, differentiation, and tumorigenesis. Ubiquitin-specific protease 7 (USP7) has been implicated in tumor development and metastasis in various malignancies through the regulation of target protein stability. In this study, we found that the enhancer of zeste homolog 2 (EZH2), which catalyzes the methylation at lysine 27 of histone H3, is a target of USP7 and is stabilized by USP7-mediated deubiquitination. In prostate cancer cells, the transcriptional repression function of EZH2 was inhibited by USP7-knockdown. Furthermore, ectopic introduction of EZH2 restored the cell migration, invasion, and sphere-forming potential of prostate cancer cells, which had been decreased by USP7-knockdown. Moreover, combined treatment with the USP7-specific inhibitor P5091 and EZH2 inhibitors, such as GSK126, EPZ6438, and DZNep, induced synergistic inhibitory effects on cell migration, invasion, and sphere-forming potential in prostate cancer cells. Collectively, our findings revealed that the promotion of the malignancy-associated characteristics of prostate cancer cells by USP7 was in part due to EZH2 stabilization. Thus, we suggest that simultaneous treatment with a USP7 inhibitor and an EZH2 inhibitor could be a rational strategy for treating EZH2-dependent cancers.

ABSTRACT Persea americana Mill., Lauraceae, commonly known as the avocado, is native to tropical and subtropical regions, including Brazil. From the leaves of P. americana, one previously undescribed flavonol glycoside (1) together with ten known flavonoids (2-11), four megastigmane glycosides (12-15) and two lignans (16-17) were isolated. Their structures were determined by extensive spectroscopic methods including 1D- and 2D-nuclear magnetic resonance and mass spectrometry data. This is the first investigation that reports megastigmane glycoside and lignan classes within the genus Persea. All the isolated compounds have been assessed through the cell survival of larval zebrafish following neomycin-induced damage and the cell viability of a House Ear Institute-Organ of Corti 1 mouse auditory cell line. Among the tested compounds, juglanin (2) and (+)-lyoniresinol (16) showed significant cell regeneration in neomycin-damaged hair cell without cellular toxicity.

Abstract The effect of water extracts of doenjang (WED) on cyclooxygenase pathway and cytokine production in lipopolysaccharide (LPS)-treated RAW 264.7 macrophage cells was investigated. WED was fractionated by ultrafiltration into five individual groups of molecular weights. All of the WED fractions significantly inhibited the production of prostaglandin E2 (PGE2) and expression of cyclooxygenase-2 (COX-2) in LPS-stimulated RAW 264.7 macrophages. Furthermore, each of the WED fractions significantly decreased production of pro-inflammatory cytokine such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) (p<0.05). The fraction between 10 to 30 kDa of WED showed the highest inhibition of pro-inflammatory cytokine production, LPS-induced COX-2 expression and PEG2 production. These results suggest that WED fractions may have the anti-inflammatory effect via the stimulus of COX-2 and TNF-α in LPS-stimulated inflammation in RAW 264.7 cells.

Abstract Schisandra sphenanthera Rehder & E.H. Wilson, Schisandraceae, is well known as a type of traditional medicine for the treatment of hepatitis, diarrhea and insomnia in Asia. It was also reported to have antiviral and anti-HIV activities. Using various chromatographic resins and isolation techniques, a new lignan (1), erythro-4-(3,4-dimethoxyphenyl)-4-hydroxy-3-methylbutan-2yl-3,4-dimethoxybenzoate, along with fifteen known compounds, were isolated from fruits of S. sphenanthera. The structures of the compounds were identified by extensive spectroscopic and spectrometric methods including 1D and 2D NMR and MS data. All the isolated compounds were evaluated for their cytotoxicity activity against Hela, HepG2 and HCT-116 cells. Among them, compound schisanlactone C showed significant cytotoxicity activity.