Transcriptomic Analysis of Newborn Hanwoo Calves: Effects of Maternal Overnutrition during Mid- to Late Pregnancy on Subcutaneous Adipose Tissue and Liver.

This study investigated the transcriptomic responses of subcutaneous adipose tissue (SAT) and liver in newborn Hanwoo calves subjected to maternal overnutrition during mid- to late gestation. Eight Hanwoo cows were randomly assigned to control and treatment groups. The treatment group received a diet of 4.5 kg of concentrate and 6.5 kg of rice straw daily, resulting in intake levels of 8.42 kg DMI, 5.69 kg TDN, and 0.93 kg CP-higher than the control group (6.07 kg DMI, 4.07 kg TDN, and 0.65 kg CP), with respective NEm values of 9.56 Mcal and 6.68 Mcal. Following birth, newly born calves were euthanized humanely as per ethical guidelines, and SAT and liver samples from newborn calves were collected for RNA extraction and analysis. RNA sequencing identified 192 genes that were differentially expressed in the SAT (17 downregulated and 175 upregulated); notably, HSPA6 emerged as the most significantly upregulated gene in the SAT and as the singular upregulated gene in the liver (adj-p value < 0.05). Additionally, differential gene expression analysis highlighted extensive changes across genes associated with adipogenesis, fibrogenesis, and stress response. The functional enrichment pathway and protein-protein interaction (PPI) unraveled the intricate networks and biological processes impacted by overnutrition, including extracellular matrix organization, cell surface receptor signaling, and the PI3K-Akt signaling pathway. These findings underscore maternal overnutrition's substantial influence on developmental pathways, suggesting profound cellular modifications with potential lasting effects on health and productivity. Despite the robust insights that are provided, the study's limitations (sample size) underscore the necessity for further research.

Weissella sp. SNUL2 as potential probiotics with broad-spectrum antimicrobial activities.

Probiotics have been applied to a wide range of bacteria, causing gastrointestinal and vaginal infections. However, probiotics generally possess limited antimicrobial spectra and are primarily utilized as dietary supplements. Recognizing the need for more versatile probiotics, this study focuses on isolating and characterizing strains suitable for antibiotic replacement. Among these strains, Weissella sp. SNUL2, derived from a traditional fermented food in Korea (i.e., Sikhae), emerged as a promising candidate. The correlation between optical density at 600 nm and colony-forming units was verified and applied in subsequent experiments. To assess the therapeutic potential of probiotics, antibacterial tests were conducted using a microplate reader to evaluate the inhibition of 60 bacterial strains (including common foodborne pathogens) induced by Weissella sp. SNUL2 cell-free supernatant (CFS). The results confirmed its broad-spectrum antibacterial properties compared to previously known probiotics. Furthermore, enzymatic treatment with proteinases (trypsin and pepsin) and a time-kill assay were conducted to elucidate the nature of the antibacterial substance in Weissella sp. SNUL2 CFS. Through sequential chromatography involving gel filtration and ion-exchange chromatography, specific fractions with enhanced antibacterial properties were identified. LC-MS/MS analysis of the secretome fraction revealed the presence of various proteins from the C39 family, peptidoglycan endopeptidases, and N-acetylmuramoyl-l-alanine amidase domain-containing protein precursors. Hence, the combined action of these proteins may contribute to Weissella sp. SNUL2's broad antimicrobial activity.

Effects of mid-to-late prepartum feed supplementation in Hanwoo beef cows on their performance, blood metabolites, and the carcass characteristics and metabolites of their neonatal calves.

Introduction: This study aimed to evaluate the implications of supplementary nutrition during the mid-to-late pregnancy on various parameters in Hanwoo cows and their subsequent neonatal calves. Materials and methods: Eight Hanwoo cows in their first parity were divided into two groups. The control group (C, 100%) received 3kg of concentrate and 5kg of rice straw throughout the pregnancy period, while the treatment group (T, 150%) increased their diet during mid-to-late pregnancy. Both performance assessments and blood metabolite analyses were performed for the pregnant cows. Neonatal calves were subjected to morphometric evaluations, blood sampling, and detailed morphometric analyses of carcasses and gastrointestinal components. Results: Performance indices of the cows showed that both Pregnancy Period (PregP) and Body Condition Score (BCS) were significantly improved with supplemental feeding (p <0.05). Improvements in Body Weight (BW) and Feed Conversion Ratio (FCR) were not statistically significant. Blood metabolite analysis for the cows revealed decreased levels of triglycerides (TGLate), non-esterified fatty acids (NEFALate), and progesterone (P4Late), with a notable increase in glucose (GluLate) levels (p <0.01). In the neonatal calves, anatomical metrics of the gastrointestinal tissues showed increased Omasum Width (OmasWdth) values in the supplemented group (p =0.053). There was significant increase of papillae and villus lengths in the rumen and small intestine (p <0.01 and p <0.05, respectively). Morphometric evaluations displayed longer body lengths (BLnth) and larger chest width (ChestWdth) in the treated calves (p <0.05 and p <0.01, respectively). Carcass characteristics showed no substantial variations between the groups, while blood analysis in the calves revealed decreased GPT levels in the nutritionally supplemented group (p<0.05). Discussion: The findings indicate that supplementing the diets of Hanwoo cows during mid-to-late pregnancy leads to significant changes in select maternal blood metabolites and influences specific anatomical and morphometric features in neonatal calves, all without significant shifts in carcass attributes.

Administration of the probiotic Lactiplantibacillus paraplantarum is effective in controlling hyperphosphatemia in 5/6 nephrectomy rat model.

AIMS: Several studies have linked gut microbes to human diseases. Most of the mechanisms by which lactic acid bacteria have beneficial effects on the human body are related to immune modulation. Controlled studies of the ability of lactic acid bacteria to absorb phosphorus directly from the intestine and thereby control serum phosphorus level in in vivo uremic animal models are limited. MATERIALS AND METHODS: We screened lactic acid bacteria living in Korean fermented foods to identify those that absorb the most phosphorus and noted Lactiplantibacillus paraplantarum KCCM 11826P. The mechanism through which better intracellular absorption of phosphorus occurs in this strain was studied using genomic DNA sequencing. After the strain was administered to 5/6 nephrectomized rats for 6 weeks, it was observed whether hyperphosphatemia had improved. KEY FINDINGS: The L. paraplantarum KCCM 11826P strain has a polyP gene cluster; thus, it absorbs phosphorus better than other bacteria and can suppress strains that produce indole. Supplementing the diets of 5/6 nephrectomized rats with this L. paraplantarum strain significantly decreased serum phosphate level (by 22 %) and reduced blood indoxyl sulphate concentration (by 40 %) compared with vehicle treatment. SIGNIFICANCE: These results suggest that Lactiplantibacillus preparations can be used for multiple purposes, such as the removal of phosphorus and uremic toxins from patients with chronic kidney disease (CKD). This study also demonstrates the novel concept of a probiotic phosphate binder.

The prolongation effect of ilaprazole-based standard triple therapy for Helicobacter pylori.

BACKGROUND: Helicobacter pylori (HP) infection causes many diseases, such as peptic ulcers, gastritis and gastric cancer, and MALToma. It has been gradually accepted that all HP-infected patients should be treated because HP is regarded as an infection. Therefore, the importance of selecting the optimal treatment regimen has increased. Although the 14-day standard triple therapy (STT) is recommended in the current guidelines, prolonging treatment duration is controversial in real practice because of inconsistent results from previous data and the risk of adverse effects. Additionally, the effect of STT using ilaprazole has not been reported until now. We aimed to compare the eradication rate between 7 and 10 days STT using ilaprazole. METHODS: A prospective randomized controlled trial was conducted, which was divided into 2 treatment groups: the control group was 7 days of STT, and the test group was 10 days of STT. The eradication regimen was 10 mg ilaprazole, 500 mg clarithromycin, and 1000 mg amoxicillin twice daily. We included patients who were diagnosed with positive results of H pylori examination. We compared the HP eradication rate according to treatment duration, CYP2C19 subtype and endoscopic diagnosis. RESULTS: We enrolled a total of 254 patients consisting of 127 patients in each treatment arm. The eradication rates of the control and test groups were 65.4% (82/127) and 74.8% (95/127), respectively, in the intention-to-treat analysis (P = .1). In the per-protocol analysis, 70.3% (83/118) and 82.6% (94/115) were eradicated in each group, which was statistically significant (P = .027). The CYP2C19 subtype was examined in 230 patients. The eradication rate was 79.2% (57/72), 75.4% (92/122), and 72.2% (26/36) in each group, which was not significantly different (P = .704). CONCLUSION: Ten-day STT was more effective than 7-day STT for HP eradication. The eradication rate was not affected by the CYP2C19 genotype.

Efficacy and Safety of a Balanced Salt Solution Versus a 0.9% Saline Infusion for the Prevention of Contrast-Induced Acute Kidney Injury After Contrast-Enhanced Computed Tomography.

RATIONALE & OBJECTIVE: We aimed to elucidate whether a balanced salt solution decreases the occurrence of contrast-induced acute kidney injury (CI-AKI) after contrast-enhanced computed tomography (CE-CT) as compared to 0.9% saline solution. STUDY DESIGN: A randomized clinical trial. SETTING & PARTICIPANTS: The study was performed in 14 tertiary hospitals in South Korea. Patients with estimated glomerular filtration rates (eGFRs) < 45 or <60 mL/min/1.73 m2 and additional risk factors (age ≥ 60 years or diabetes) who were undergoing scheduled CE-CT were included from December 2016 to December 2018. INTERVENTION: An open-label intervention was performed. The study group received a balanced salt solution and the control group received 0.9% saline solution as prophylactic fluids for CE-CT. OUTCOMES: The primary outcome was CI-AKI, defined by creatinine level elevation ≥ 0.5 mg/dL or 25% from baseline within 48 to 72 hours after CE-CT. Secondary outcomes included AKI defined based on the KDIGO (Kidney Disease: Improving Global Outcomes) guideline, eGFR changes, death, or requiring dialysis within 6 months after CE-CT. RESULTS: 493 patients received the study fluids. The control and study groups included 251 and 242 patients, respectively. The occurrence of CI-AKI in the study (10 [4.2%]) and control (17 [6.8%]) groups was not significantly different (P = 0.27). No significant difference was present for the secondary outcomes; AKI by the KDIGO definition (study: 19 [7.9%], control: 27 [10.8%]; P = 0.33), death/dialysis (study: 11 [4.7%], control: 9 [3.7%]; P = 0.74), and eGFR changes (study: 0.1 ± 0.2 mg/dL, control: 0.3 ± 2.8 mg/dL; P = 0.69). LIMITATIONS: This study failed to meet target enrollment. CONCLUSIONS: The risk for CI-AKI was similar after administration of a balanced salt solution and after use of 0.9% saline solution during CE-CT in higher-risk patients. FUNDING: This study was funded by CJ Healthcare (CS2015_0046). TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT02799368.

Significance of Soluble CD93 in Type 2 Diabetes as a Biomarker for Diabetic Nephropathy: Integrated Results from Human and Rodent Studies.

Cluster of differentiation 93 (CD93) is a glycoprotein expressed in activated endothelial cells. The extracellular portion of CD93 can be secreted as a soluble form (sCD93) under inflammatory conditions. As diabetic nephropathy (DN) is a well-known inflammatory disease, we hypothesized that sCD93 would be a new biomarker for DN. We prospectively enrolled 97 patients with type 2 diabetes and evaluated the association between serum sCD93 and DN prevalence. The association between CD93 and development of DN was investigated using human umbilical cord endothelial cells (HUVECs) in vitro and diabetic db/db mice in vivo. Subjects with higher sCD93 levels had a lower estimated glomerular filtration rate (eGFR). The sCD93 level was an independent determinant of both the albumin-to-creatinine ratio (ACR) and the eGFR. The risk of prevalent DN was higher in the high sCD93 group (adjusted odds ratio 7.212, 95% confidence interval 1.244-41.796, p = 0.028). In vitro, CD93 was highly expressed in HUVECs and both CD93 expression and secretion were upregulated after lipopolysaccharides (LPS) stimulation. In vivo, peritoneal and urine sCD93 levels and the renal glomerular expression of CD93 were significantly higher in the db/db mice than in the control db/m+ mice. These results suggest the potential of sCD93 as a candidate biomarker associated with DN.

The Utility of the Random Urine Uric Acid-to-Creatinine Ratio for Patients with Gout Who Need Uricosuric Agents: Retrospective Cross-Sectional Study.

BACKGROUND: The 24-hour uric acid excretion measurement is important in assessing disease status and helping to select the appropriate uric acid-lowering agent for patients with gout, however, it is inconvenient. The authors investigated the efficacy of the random urine uric acid-to-creatinine (UA/CR) ratio to screen the patients who under-secreted 24-hour urine uric acid. METHODS: This was a retrospective cross-sectional study. Ninety patients with gout, without undergoing uric acid-lowering treatment were enrolled. Twenty-four-hour urine and random urine samples were obtained on the same day. Six hundred mg of uric acid in the 24-hour urine sample was used as a standard for distinguishing between over and under-excretion groups. RESULTS: The random urinary UA/CR ratio showed positive correlation with 24-hour urine uric acid excretion (γ = 0.398, P < 0.001). All the patients with the random UA/CR less than 0.2 excreted less than 600 mg uric acid in 24-hour urine collection. When the random urine UA/CR ratio < 0.2 was regarded as a positive result, the positive predictive value, negative predictive value, sensitivity, and specificity in the uric acid under-excretion were 100% (8 of 8), 64.6% (53 of 82), 21.6% (8 of 37), and 100% (53 of 53), respectively. CONCLUSION: There is a moderate positive correlation between the random urinary UA/CR ratio and 24-hour urine uric acid excretion, so that UA/CR ratio may not be a good predictor of 24-hour urine uric acid excretion. However, the random urine UA/CR ratio 0.2 can be a useful predictor to screen the gouty patients who need to be treated with uricosuric drugs.

Low-normal hemoglobin levels and anemia are associated with increased risk of end-stage renal disease in general populations: A prospective cohort study.

BACKGROUND: The impact of low-normal hemoglobin (Hb) levels and anemia on the risk of end-stage renal disease (ESRD) in general populations has rarely been examined. METHODS: 510,620 Korean adults aged 40-80 years without known chronic kidney disease (CKD) underwent health examinations during 2002-2003 and were followed-up until 2013. Incidence of ESRD was identified by hospital discharge and clinical visit records. RESULTS: During a mean follow-up of 10.5, 575 women and 1047 men were diagnosed with ESRD. Lower Hb levels were associated with an increased risk of ESRD at given severity of albuminuria and at given estimated glomerular filtration rate (eGFR). Hb 13-13.9 g/dL in men, Hb 11-11.9 g/dL in women, and trace albuminuria assessed by dipstick urinalysis were associated with more than doubled risk. The risk associated with lower Hb was stronger in older (≥60 years) than younger women. Among 349,993 participants with information on eGFR, the multivariable-adjusted HRs associated with 1 g/dL lower Hb in participants with eGFR values ≥60, 30-59, and <30 mL/min/1.73 m2 were 1.34 (95% CI, 1.17-1.54), 1.55 (1.38-1.74), and 1.75 (1.47-2.09), respectively (Pinteraction between eGFR groups = .06). CONCLUSIONS: Low-normal Hb levels and anemia are risk factors for ESRD incidence in person without CKD and for CKD progression to ESRD. Lower Hb increases the risk of ESRD through synergistic biological interactions with lower eGFR and albuminuria. The impacts of lower Hb may be stronger in older than younger women. Proper management and screening at earlier stage of Hb decline and anemia might reduce the burden of CKD.

Effects of Excessive Body Fat Accumulation on Long-Term Outcomes During Peritoneal Dialysis.

Background:Significant body fat accumulation is an inevitable but potentially serious problem in peritoneal dialysis (PD) patients. Whether excessive fat gain predicts long-term outcomes in these patients remains unknown.Methods:In this prospective cohort study (n = 297), the associations of excessive fat accumulation with patient survival and PD failure rate were examined. Based on dialysis duration at the time of study enrollment, patients were divided into short- (< 2 years) and long-term (> 2 years) groups. Body weight (BW) and body composition were measured twice, 12.8 ± 4.6 months apart. Excessive fat accumulation was defined as a 1-year change in the percentage of body fat (ΔPBF) over the highest quartile (5.0% for men, 5.4% for women).Results:Substantial 1-year increases in BW and PBF were observed only in the short-term group (p < 0.001 and p = 0.027, respectively); changes were insignificant in the long-term group. In the short-term group, the ΔPBF was associated closely with unfavorable baseline metabolic profiles, including old age, diabetes, obesity, elevated blood pressure, and edema. Accordingly, the mortality rate was significantly higher in patients with, than in those without, excessive fat accumulation (hazard ratio [HR] 3.26, 95% confidence interval [CI], 1.05 - 10.26). It also increased the incident risk of PD failure 2.22-fold (95% CI, 1.08 - 4.54), even after adjustment for diabetes, obesity, and fluid status. In the long-term group, fat gain had no impact on long-term prognosis.Conclusions:Excessive fat accumulation during the early period of PD was associated with baseline unhealthy metabolic profiles, a higher mortality rate, and a higher PD failure rate, independent of baseline obesity and fluid status.

Small gastric hyperplastic polyp with acute bleeding as an unusual presentation of malignancy: A case report.

RATIONALE: Gastric hyperplastic polyps are frequently found on upper gastrointestinal endoscopy and usually asymptomatic. PATIENTS CONCERNS: A 65-year-old man visited the emergency department due to melena. Emergency upper endoscopy revealed a semi-pedunculated polyp measuring 1.2 cm in diameter with blood oozing. We resected the polyp using snare polypectomy. Ulceration was noted on the polypectomy specimen and was thought to be a bleeding focus. DIAGNOSES: Histopathologic findings revealed hyperplastic polyp with focal well-differentiated adenocarcinoma in the ulcerated area and involvement of the lateral resection margin by carcinoma. INTERVENTION: We performed additional endoscopic resection using endoscopic submucosal dissection at the previous polypectomy site. OUTCOME: At 1 year follow up, no recurrence or other distant metastasis was detected. LESSONS: This is a rare case of upper gastrointestinal bleeding from a small gastric hyperplastic polyp, which was found to be adenocarcinoma. When bleeding small gastric polyps are encountered during endoscopy, the possibility of malignancy and wider resection should be considered.

Determination of the optimal target level of proteinuria in the management of patients with glomerular diseases by using different definitions of proteinuria.

Proteinuria is a major determinant of adverse renal outcome, and its reduction slows renal progression in glomerular diseases. However, the optimal target of proteinuria in glomerular diseases is unclear, and discrepancies in the definition of proteinuria produce ambiguous findings. Here we investigated the optimal target of proteinuria by using different definitions of proteinuria. We analyzed 574 IgA nephropathy (IgAN), 175 membranous nephropathy (MGN), and 177 focal segmental glomerulosclerosis (FSGS) cases from 3 Korean kidney centers. We evaluated the impact of proteinuria on renal outcome with 2 definitions: time-average proteinuria (TAP) and time-varying proteinuria (TVP). The endpoint was renal progression, defined as a 50% decline in glomerular filtration rate or end-stage renal disease. During a median follow-up of 57.3 months, the primary outcome occurred in 54 patients with IgAN, 26 with MGN, and 30 with FSGS. Multivariate Cox regression using TAP indicated that there was a linear association between proteinuria and risk of renal progression in IgAN. However, moderate proteinuria was not associated with an increased risk of renal progression in MGN and FSGS. In contrast, the analysis by TVP showed that the risk significantly increased in proportion to proteinuria during follow-up in all 3 diseases. Our findings suggest that TVP-based model can delineate association between proteinuria and risk of renal progression better than TAP-based model, considering that TVP reflects the dynamic change of proteinuria over time. Thus, proteinuria reduction to the lowest possible level is required to improve renal outcomes in patients with glomerular diseases.

Efficacy and safety of a balanced salt solution versus a 0.9% saline infusion for the prevention of contrast-induced acute kidney injury (BASIC trial): a study protocol for a randomized controlled trial.

BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is one of the most common causes of iatrogenic kidney injury and, therefore, its prevention is an important issue. However, whether the administration of 0.9% saline is the optimal prophylaxis method remains uncertain due to its supra-physiologic chloride component. In particular, recent studies suggest that chloride-restricted solutions showed superiority over 0.9% saline in several clinical settings. METHODS/DESIGN: The investigators designed a multicenter randomized controlled trial to compare the efficacy of a balanced salt solution and 0.9% saline in CI-AKI prophylaxis. This study will recruit patients who are scheduled for contrast-enhanced computed tomography (CT) scans with CI-AKI prophylaxis. In this study, participants will be randomized into two study arms; the study group will receive a balanced salt solution, and the control group will receive 0.9% saline. Fluids will be administered as designated in the protocol before and after the CT scan, and an evaluation of baseline clinical status will be performed by obtaining blood and urine samples. During the follow-up visits, the incidence of CI-AKI and long-term outcomes, including the start of renal replacement therapy or all-cause mortality, will be assessed. DISCUSSION: To our knowledge, this study will be the first study assessing the preventive value of a balanced salt solution over 0.9% saline for CI-AKI. If the trial shows that the balanced salt solution is as effective for CI-AKI prophylaxis as 0.9% saline, the use of the balanced salt solution could be promoted due to the reduced possibility of consequent metabolic acidosis compared to 0.9% saline. TRIALS REGISTRATION: ClinicalTrials.gov, ID: NCT02799368 . Registered on 14 June 2016.

Relationship between Chronic Kidney Disease and Depression in Elderly Koreans Using the 2013 Korea National Health and Nutrition Examination Survey Data.

BACKGROUND: Depression is prevalent in patients with chronic kidney disease (CKD) and continues to increase in elderly adults. Therefore, the aim of our study was to examine the relationship between CKD and depression in older patients. METHODS: We conducted a cross-sectional study based on 2013 Korea National Health and Nutrition Examination Survey data. In total, data of 973 subjects aged ≥65 years were analyzed, and the estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. RESULTS: The prevalence of depression in older adults was 4.1% in men and 8.8% in women (P=0.004). The prevalence of depression did not differ according to CKD stage in women (normal eGFR and CKD stages 1 and 2 women, 41/474 [8.6%]) vs. CKD stages 3-5 women, 6/63 [9.5%]); however, the prevalence of depression in men with CKD stages 3-5 (8/83 [9.6%]) was significantly higher than in men with normal eGFR and CKD stage 1 and 2 (10/353 [2.8%], P=0.010). Multivariate logistic regression analysis showed that the odds ratio for depression in men with CKD stages 3-5 was 3.822 (95% confidence interval, 1.229 to 11.879) after adjusting for social status and chronic diseases (P=0.021). CONCLUSION: The prevalence of depression was higher in elderly women than in men, while the prevalence of depression increased in elderly men with CKD stages 3-5 and was almost equal to that of women. Therefore, elderly men with progressive renal function impairment should be counseled and monitored for psychological problems.

Effect of Icodextrin Solution on the Preservation of Residual Renal Function in Peritoneal Dialysis Patients: A Randomized Controlled Study.

Although icodextrin solution has been highlighted in the fluid management compared to glucose-based solutions, proof of a beneficial effect of icodextrin solution on residual renal function (RRF) is lacking. We conducted a multicenter prospective randomized controlled open-label trial to investigate whether icodextrin solution can preserve RRF.One hundred patients with urine volume ≥750 mL/day from 8 centers in Korea were randomly assigned to receive 1 exchange of icodextrin solution for a ≥8 hour-dwell time and 2 exchanges of 1.5% glucose-based biocompatible neutral pH solution or 1 exchange of ≥2.5% and 2 exchanges of 1.5% glucose-based biocompatible solutions. Using mixed-effects general linear models, we analyzed changes in residual glomerular filtration rate (GFR) and daily urine volume at 1 year.Forty-nine patients were assigned to the icodextrin group and 51 to the glucose solution group. During follow-up, the slope of the decline in residual GFR was -0.170 mL/min/month/1.73 m² in the icodextrin group, while it was -0.155 mL/min/month/1.73 m² in the glucose solution group (95% confidence interval [CI], -0.06 to 0.10; P = 0.701). Daily urine volume decreased faster in the glucose solution group than in the icodextrin group (-31.02 vs -11.88 mL per month; 95% CI, -35.85 to -2.44; P = 0.025). Results were consistent when we analyzed using intention-to-treat and per protocol principles. There were no differences in fluid status, peritoneal ultrafiltration, and peritoneal transport between groups during follow-up.This study clearly showed that icodextrin solution preserves residual urine volume better than glucose solution.

Dysregulation of MicroRNA-196b-5p and MicroRNA-375 in Gastric Cancer.

PURPOSE: Dysregulated microRNAs (miRNAs) can contribute to cancer development by leading to abnormal proliferation of cells, apoptosis, and differentiation. Although several miRNAs that are related to gastric cancer have been identified, the reported results have been inconsistent. The aim of this study was to determine miRNA expression profiles and validate miRNAs up- and down-regulated in gastric cancer. MATERIALS AND METHODS: We evaluated 34 primary gastric cancer tissues and paired adjacent nontumorous gastric tissues. Total RNA was extracted, and low-molecular-weight RNAs (<200 nucleotides) were isolated for further analysis. Two pairs of tissues were processed for GeneChip microarray analysis, and the identified up- and down-regulated miRNAs were validated by real-time quantitative polymerase chain reaction (qPCR). RESULTS: In the set of differentially expressed miRNAs, 5 were overexpressed by more than 2 fold, and 5 were reduced by 2 fold or less in gastric cancer tissues compared with normal gastric tissues. Four of these miRNAs (miR-196b-5p, miR-375, miR-483-5p, and miR-486-5p) were then validated by qPCR, and the relative expression levels of 2 miRNAs (miR-196b-5p and miR-375) were significantly different between cancer and normal tissues. CONCLUSIONS: Our results revealed that the expression of miR-196b-5p and miR-375 significantly correlates with gastric cancer. These miRNAs could therefore serve as diagnostic biomarkers of gastric cancer.

Excessive Weight Gain during the First Year of Peritoneal Dialysis Is Associated with Inflammation, Diabetes Mellitus, and a Rapid Decrease in Residual Renal Function.

OBJECTIVES: Significant weight gain is a potential problem in most patients starting peritoneal dialysis (PD); however, few studies have explored the clinical effects of increased body weight (BW) in these patients. We evaluated the effect of excess weight gain during the first year after PD on residual renal function (RRF). METHODS: A total of 148 incident PD patients were analyzed in a longitudinal observational study. The mean duration of follow-up was 23.8 months. RRF was measured at baseline (within 1 month of starting PD) and thereafter at 6-month intervals for 2-3 years or until loss of RRF. BW was measured at the time of RRF measurement, and excess weight gain was defined as a BW increase over the median value (3.0%). RESULTS: The median 1-year increase in BW was 2.3kg (IQR, 1.01-4.58) or 3.0% (IQR, 1.13-5.31). The mean slope of RRF decline was -0.068 ± 0.053 mL/min/month/1.73m2, and RRF loss developed in 48 patients at a mean follow-up time of 19.4 ± 6.8 months. Patients with BW increases > 3.0% showed significantly increased RRF decline rate compared to those without excess weight gain (p<0.001), and the BW increase (%/year) correlated significantly with higher hs-CRP levels and RRF decline rate. High systolic blood pressure, diabetes, large amount of proteinuria and excess BW gain significantly influenced the RRF decline rate. Also, it increased the risk of RRF loss by 4.17-fold (95% confidence intervals, 1.87-9.28; p<0.001). CONCLUSIONS: Excess weight gain during the first year of PD was closely linked to systemic inflammation, diabetes and rapid decline in RRF.

Relationship between Stage of Chronic Kidney Disease and Sarcopenia in Korean Aged 40 Years and Older Using the Korea National Health and Nutrition Examination Surveys (KNHANES IV-2, 3, and V-1, 2), 2008-2011.

BACKGROUND: Protein-energy wasting is common in patients with end-stage kidney disease. However, few studies have examined the relationship between early stages of chronic kidney disease (CKD) and sarcopenia. METHODS: We conducted a cross-sectional study based on data in the Korea National Health and Nutrition Examination Survey, 2008-2011. In total, 11,625 subjects aged 40 years or older who underwent dual-energy X-ray absorptiometry were analyzed. Sarcopenia was defined based on values of appendicular skeletal muscle mass as a percentage of body weight (ASM/Wt) two standard deviations below the gender-specific mean for young adults. Estimated glomerular filtration rates (eGFR) were calculated using the CKD-EPI equation. RESULTS: Mean age, body mass index (BMI), and HOMA-IR were higher and caloric intake, physical activity, and vitamin D level were lower in the sarcopenia groups in both men and women. As the stage of CKD increased, the prevalence of sarcopenia increased, even in the early stages of CKD (normal and CKD1, 2, and 3-5: 2.6%, 5.6%, and 18.1% in men and 5.3%, 7.1%, and 12.6% in women, respectively; p < 0.001). In addition, a correlation analysis showed that GFR and ASM/Wt had significant correlations in both men and women. Logistic regression analyses, after adjusting for age, BMI, caloric intake, log(physical activity), vitamin D level, and log(HOMA-IR), showed that the odds ratio for sarcopenia with respect to CKD 3-5 was 1.93 (95% CI = 1.02-3.68) in men but was not statistically significant in women. CONCLUSIONS: The prevalence of sarcopenia was higher in elderly Korean patients with even mildly reduced kidney function. Stage of CKD was associated with an increased prevalence of sarcopenia in men but not women. Thus, we should evaluate the risk of sarcopenia and work to prevent it, even in patients with early CKD.

Podocyte hypertrophy precedes apoptosis under experimental diabetic conditions.

Podocyte hypertrophy and apoptosis are two hallmarks of diabetic glomeruli, but the sequence in which these processes occur remains a matter of debate. Here we investigated the effects of inhibiting hypertrophy on apoptosis, and vice versa, in both podocytes and glomeruli, under diabetic conditions. Hypertrophy and apoptosis were inhibited using an epidermal growth factor receptor inhibitor (PKI 166) and a pan-caspase inhibitor (zAsp-DCB), respectively. We observed significant increases in the protein expression of p27, p21, phospho-eukaryotic elongation factor 4E-binding protein 1, and phospho-p70 S6 ribosomal protein kinase, in both cultured podocytes exposed to high-glucose (HG) medium, and streptozotocin-induced diabetes mellitus (DM) rat glomeruli. These increases were significantly inhibited by PKI 166, but not by zAsp-DCB. In addition, the amount of protein per cell, the relative cell size, and the glomerular volume were all significantly increased under diabetic conditions, and these changes were also blocked by treatment with PKI 166, but not zAsp-DCB. Increased protein expression of cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase, together with increased Bax/Bcl-2 ratios, were also observed in HG-stimulated podocytes and DM glomeruli. Treatment with either zAsp-DCB or PKI 166 resulted in a significant attenuation of these effects. Both PKI 166 and zAsp-DCB also inhibited the increase in number of apoptotic cells, as assessed by Hoechst 33342 staining and TUNEL assay. Under diabetic conditions, inhibition of podocyte hypertrophy results in attenuated apoptosis, whereas blocking apoptosis has no effect on podocyte hypertrophy, suggesting that podocyte hypertrophy precedes apoptosis.