Factors predicting different times for brushing teeth during the day: multilevel analyses.

BACKGROUND: The most effective and simple intervention for preventing oral disease is toothbrushing. However, there is substantial variation in the timing of brushing teeth during the day. We aimed to identify a comprehensive set of predictors of toothbrushing after lunch and after dinner and estimated contextual (i.e., geographic) variation in brushing behavior at different times of the day. METHODS: We constructed a conceptual framework for toothbrushing by reviewing health behavior models. The main data source was the 2017 Community Health Survey. We performed a four-level random intercept logistic regression to predict toothbrushing behavior. (individual, household, Gi/Gun/Gu, and Si/Do). RESULTS: Individuals under 30 years of age had higher likelihood of brushing after lunch, while brushing after dinner was higher among those aged 40-79 years. People engaged in service/sales, agriculture/fishing/labor/mechanics, as well as student/housewife/unemployed were 0.60, 0.41, and 0.49 times less likely to brush their teeth after lunch, respectively, compared to those working in the office, but the gap narrowed to 0.97, 0.96, 0.94 for brushing after dinner. We also found significant area-level variations in the timing of brushing. CONCLUSIONS: Different patterns in association with various factors at individual-, household- and Si/Gun/Gu-levels with toothbrushing after lunch versus toothbrushing after dinner suggests a need for tailored interventions to improve toothbrushing behavior depending on the time of day.

Urine-Derived Stem Cell-Secreted Klotho Plays a Crucial Role in the HK-2 Fibrosis Model by Inhibiting the TGF-ß Signaling Pathway.

Renal fibrosis is an irreversible and progressive process that causes severe dysfunction in chronic kidney disease (CKD). The progression of CKD stages is highly associated with a gradual reduction in serum Klotho levels. We focused on Klotho protein as a key therapeutic factor against CKD. Urine-derived stem cells (UDSCs) have been identified as a novel stem cell source for kidney regeneration and CKD treatment because of their kidney tissue-specific origin. However, the relationship between UDSCs and Klotho in the kidneys is not yet known. In this study, we discovered that UDSCs were stem cells that expressed Klotho protein more strongly than other mesenchymal stem cells (MSCs). UDSCs also suppressed fibrosis by inhibiting transforming growth factor (TGF)-ß in HK-2 human renal proximal tubule cells in an in vitro model. Klotho siRNA silencing reduced the TGF-inhibiting ability of UDSCs. Here, we suggest an alternative cell source that can overcome the limitations of MSCs through the synergetic effect of the origin specificity of UDSCs and the anti-fibrotic effect of Klotho.

Collecting Duct-Specific CR6-Interacting Factor-1-Deletion Aggravates Renal Inflammation and Fibrosis Induced by Unilateral Ureteral Obstruction.

Although inflammation and fibrosis, which are key mechanisms of chronic kidney disease, are associated with mitochondrial damage, little is known about the effects of mitochondrial damage on the collecting duct in renal inflammation and fibrosis. To generate collecting duct-specific mitochondrial injury mouse models, CR6-interacting factor-1 (CRIF1) flox/flox mice were bred with Hoxb7-Cre mice. We evaluated the phenotype of these mice. To evaluate the effects on unilateral ureteral obstruction (UUO)-induced renal injury, we divided the mice into the following four groups: a CRIF1flox/flox (wild-type (WT)) group, a CRIF1flox/flox-Hob7 Cre (CRIF1-KO) group, a WT-UUO group, and a CRIF1-KO UUO group. We evaluated the blood and urine chemistries, inflammatory and fibrosis markers, light microscopy, and electron microscopy of the kidneys. The inhibition of Crif1 mRNA in mIMCD cells reduced oxygen consumption and membrane potential. No significant differences in blood and urine chemistries were observed between WT and CRIF1-KO mice. In UUO mice, monocyte chemoattractant protein-1 and osteopontin expression, number of F4/80 positive cells, transforming growth factor-ß and α-smooth muscle actin staining, and Masson's trichrome staining were significantly higher in the kidneys of CRIF1-KO mice compared with the kidneys of WT mice. In sham mice, urinary 8-hydroxydeoxyguanosine (8-OHDG) was higher in CRIF1-KO mice than in WT mice. Moreover, CRIF1-KO sham mice had increased 8-OHDG-positive cell recruitment compared with WT-sham mice. CRIF1-KO-UUO kidneys had increased recruitment of 8-OHDG-positive cells compared with WT-UUO kidneys. In conclusion, collecting duct-specific mitochondrial injury increased oxidative stress. Oxidative stress associated with mitochondrial damage may aggravate UUO-induced renal injury.

Mitochondrial Dysfunction in Podocytes Caused by CRIF1 Deficiency Leads to Progressive Albuminuria and Glomerular Sclerosis in Mice.

Recent studies have implicated mitochondrial disruption in podocyte dysfunction, which is a characteristic feature of primary and diabetic glomerular diseases. However, the mechanisms by which primary mitochondrial dysfunction in podocytes affects glomerular renal diseases are currently unknown. To investigate the role of mitochondrial oxidative phosphorylation (OxPhos) in podocyte dysfunction, glomerular function was examined in mice carrying a loss of function mutation of the gene encoding CR6-interacting factor-1 (CRIF1), which is essential for intramitochondrial production and the subsequent insertion of OxPhos polypeptides into the inner mitochondrial membrane. Homozygotic deficiency of CRIF1 in podocytes resulted in profound and progressive albuminuria from 3 weeks of age; the CRIF1-deficient mice also developed glomerular and tubulointerstitial lesions by 10 weeks of age. Furthermore, marked glomerular sclerosis and interstitial fibrosis were observed in homozygous CRIF1-deficient mice at 20 weeks of age. In cultured mouse podocytes, loss of CRIF1 resulted in OxPhos dysfunction and marked loss or abnormal aggregation of F-actin. These findings indicate that the OxPhos status determines the integrity of podocytes and their ability to maintain a tight barrier and control albuminuria. Analyses of the glomerular function of the podocyte-specific primary OxPhos dysfunction model mice demonstrate a link between podocyte mitochondrial dysfunction, progressive glomerular sclerosis, and tubulointerstitial diseases.

Omega-3 Polyunsaturated Fatty Acid Attenuates Uremia-Induced Brain Damage in Mice.

Although the cause of neurological disease in patients with chronic kidney disease (CKD) has not been completely identified yet, recent papers have identified accumulated uremic toxin as its main cause. Additionally, omega-3 polyunsaturated fatty acid (ω-3 PUFA) plays an important role in maintaining normal nerve function, but its protective effects against uremic toxin is unclear. The objective of this study was to identify brain damage caused by uremic toxicity and determine the protective effects of ω-3 PUFA against uremic toxin. We divided mice into the following groups: wild-type (wt) sham (n = 8), ω-3 PUFA sham (n = 8), Fat-1 sham (n = 8), ischemia-reperfusion (IR) (n = 20), and ω-3 PUFA+IR (n = 20) Fat-1+IR (n = 20). Brain tissue, kidney tissue, and blood were collected three days after the operation of mice (sham and IR operation). This study showed that Ki67 and neuronal nuclei (NeuN) decreased in the brain of uremic mice as compared to wt mice brain, but increased in the ω-3 PUFA-treated uremic mice and the brain of uremic Fat-1 mice as compared to the brain of uremic mice. The pro-apoptotic protein expressions were increased, whereas anti-apoptotic protein expression decreased in the brain of uremic mice as compared to wt mice brain. However, apoptotic protein expression decreased in the ω-3 PUFA-treated uremic mice and the brain of uremic Fat-1 mice as compared to the brain of uremic mice. Furthermore, the brain of ω-3 PUFA-treated uremic mice and uremic Fat-1 mice showed increased expression of p-PI3K, p-PDK1, and p-Akt as compared to the brain of uremic mice. We confirm that uremic toxin damages the brain and causes cell death. In these injuries, ω-3 PUFA plays an important role in neuroprotection through PI(3)K-Akt signaling.

Ion-Selective Carbon Nanotube Field-Effect Transistors for Monitoring Drug Effects on Nicotinic Acetylcholine Receptor Activation in Live Cells.

We developed ion-selective field-effect transistor (FET) sensors with floating electrodes for the monitoring of the potassium ion release by the stimulation of nicotinic acetylcholine receptors (nAChRs) on PC12 cells. Here, ion-selective valinomycin-polyvinyl chloride (PVC) membranes were coated on the floating electrode-based carbon nanotube (CNT) FETs to build the sensors. The sensors could selectively measure potassium ions with a minimum detection limit of 1 nM. We utilized the sensor for the real-time monitoring of the potassium ion released from a live cell stimulated by nicotine. Notably, this method also allowed us to quantitatively monitor the cell responses by agonists and antagonists of nAChRs. These results suggest that our ion-selective CNT-FET sensor has potential uses in biological and medical researches such as the monitoring of ion-channel activity and the screening of drugs.

Association of plasma level of growth differentiation factor-15 and clinical outcome after intraarterial thrombectomy.

BACKGROUND AND PURPOSE: As intraarterial thrombectomy (IAT) has been actively practiced, blood biomarkers that can predict outcomes after IAT have drawn attention. Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine and the levels are increased during inflammation or other pathological conditions of various tissues, including the brain. However, GDF-15 levels have not been reported as a biomarker for IAT outcomes. This study was performed to evaluate whether GDF-15 was related to the extent of brain damage and whether it could predict patient prognosis after IAT. METHODS: Patients who showed large arterial occlusion and significant diffusion-perfusion mismatch on imaging underwent IAT. A total of 62 patients who underwent IAT and had blood samples for GDF-15 measurements were enrolled from July 2013 to May 2015. We assessed the infarct severity by consecutive changes on the National Institutes of Health Stroke Scale (NIHSS) during admission and the size of the infarction on brain imaging. Modified Rankin Scale scores (mRS) from 0 to 2 were considered good outcomes, representing functional independence at discharge and three months later. RESULTS: The levels of GDF-15 at the time of admission were significantly correlated with the NIHSS scored at 24 hours (r = 0.306, p = 0.016), three days after IAT (r = 0.261, p = 0.041), and at discharge (r = 0.266, p = 0.037), as well as the infarct size on diffusion-weighted image taken 24 h after IAT (r = 0.452, p = 0.001), but the levels were not correlated with the initial NIHSS or the infarct size before IAT. Multiple logistic regression showed that GDF-15 levels were an independent predictor of functional independence (mRS 0 - 2) at discharge (p = 0.028) and three months after IAT (p = 0.019). Other factors that could predict prognosis were good collateral status on the initial brain angiography and rapid recanalization within six hours from symptom onset. CONCLUSION: The GDF-15 level at the time of admission showed a significant positive correlation with the severity of cerebral damage and clinical outcome after IAT. This suggests that GDF-15 can provide useful prognostic information for patients who successfully underwent IAT in an emergency setting.

Rifabutin and Furazolidone Could Be the Candidates of the Rescue Regimen for Antibiotic-Resistant H. pylori in Korea.

Background/Aim. In Korea, the rate of Helicobacter pylori (H. pylori) eradication has declined steadily as a result of increasing resistance to antibiotics, especially dual resistance to clarithromycin and metronidazole. However, microbiological culture data on drug-resistant H. pylori is lacking. This study evaluated the antimicrobial efficacy of candidate antibiotics against resistant H. pylori strains. Methods. After retrospectively reviewing the data from the Helicobacter Registry in Gil Medical Center (GMC) and Asan Medical Center (AMC), along with 4 reference strains, we selected the 31 single- or multidrug-resistant strains. The susceptibility of the H. pylori strains to seven antibiotics (clarithromycin, metronidazole, levofloxacin, amoxicillin, tetracycline, rifabutin, and furazolidone) and minimum inhibitory concentration were tested using the broth microdilution technique. Results. Among 31 antibiotic resistance strains for H. pylori, there were no strains resistant to rifabutin or furazolidone, which had MICs of <0.008 and 0.5 µg/mL, respectively. Only one tetracycline-resistant strain was found (MIC < 2 µg/mL). Amoxicillin and levofloxacin were relatively less effective against the H. pylori strains compared to rifabutin or furazolidone (resistance rates 22.6%, 1.9%, respectively). Tetracycline showed the relatively low resistance rates (3.2%) for H. pylori strains. Conclusions. Therefore, along with tetracycline which has already been used as a component for second-line eradication regimen for Helicobacter, rifabutin and furazolidone, alone or in combination, could be used to eradicate antibiotic-resistant H. pylori strains where drug-resistant Helicobacter spp. are increasing.

The age-related characteristics of adults with asthma who visited emergency departments in Korea from 2007 to 2012.

BACKGROUND: Understanding the patterns of emergency department (ED) visits of patients with asthma is important for disease control and prevention of exacerbations. OBJECTIVE: This study aimed to investigate the characteristics of adult patients who visited EDs because of their asthma. METHODS: Patients with asthma, ages ≥19 years old, who visited 117 EDs throughout Korea between January 2007 and December 2012 were identified in the National Emergency Department Information System (NEDIS) data base using the International Classification of Disease, 10th revision, codes J45 (asthma) and J46 (status asthmaticus). RESULTS: A total of 97,835 adult patients with asthma visited 117 EDs throughout Korea during the study period. There was a slight female preponderance (male-to-female ratio, 1:1.09). The number of patients aged 70-79-years-old was 28,031 (28.7%), the highest among the patients with asthma. ED visits showed a seasonal distribution, with most occurring in winter and spring, followed by autumn. The seasonal distribution varied by age; most patients ages 19-49 years presented in autumn (September), whereas those patients ages ≥50 years presented to the ED most often in winter. Overall, 65.5% of patients were admitted to the hospital, including 12.6% admitted to an intensive care unit (ICU). Overall, 209 patients (0.2%) died. The rates of hospital admission to general wards and ICUs were highest in those patients ≥70 years old; this group also had the highest mortality rate. CONCLUSION: In this nationwide study, which spanned 6 years, of adult patients with asthma, we observed an age-specific seasonal pattern of ED visits. Identifying the causes of age-related deterioration and seasonal visits to the ED will help prevent asthma symptoms and reduce medical costs.

Hepatic transcriptional changes in critical genes for gluconeogenesis following castration of bulls.

OBJECTIVE: This study was performed to understand transcriptional changes in the genes involved in gluconeogenesis and glycolysis pathways following castration of bulls. METHODS: Twenty Korean bulls were weaned at average 3 months of age, and castrated at 6 months. Liver tissues were collected from bulls (n = 10) and steers (n = 10) of Korean cattle, and hepatic gene expression levels were measured using quantitative real-time polymerase chain reaction. We examined hepatic transcription levels of genes encoding enzymes for irreversible reactions in both gluconeogenesis and glycolysis as well as genes encoding enzymes for the utilization of several glucogenic substrates. Correlations between hepatic gene expression and carcass characteristics were performed to understand their associations. RESULTS: Castration increased the mRNA (3.6 fold; p<0.01) and protein levels (1.4 fold; p< 0.05) of pyruvate carboxylase and mitochondrial phosphoenolpyruvate carboxykinase genes (1.7 fold; p<0.05). Hepatic mRNA levels of genes encoding the glycolysis enzymes were not changed by castration. Castration increased mRNA levels of both lactate dehydrogenase A (1.5 fold; p<0.05) and lactate dehydrogenase B (2.2 fold; p<0.01) genes for lactate utilization. Castration increased mRNA levels of glycerol kinase (2.7 fold; p<0.05) and glycerol-3-phosphate dehydrogenase 1 (1.5 fold; p<0.05) genes for glycerol utilization. Castration also increased mRNA levels of propionyl-CoA carboxylase beta (mitochondrial) (3.5 fold; p<0.01) and acyl-CoA synthetase short chain family member 3 (1.3 fold; p = 0.06) genes for propionate incorporation. CONCLUSION: Castration increases transcription levels of critical genes coding for enzymes involved in irreversible gluconeogenesis reactions from pyruvate to glucose and enzymes responsible for incorporation of glucogenic substrates including lactate, glycerol, and propionate. Hepatic gluconeogenic gene expression levels were associated with intramuscular fat deposition.

Effects of deoxynivalenol- and zearalenone-contaminated feed on the gene expression profiles in the kidneys of piglets.

OBJECTIVE: Fusarium mycotoxins deoxynivalenol (DON) and zearalenone (ZEN), common contaminants in the feed of farm animals, cause immune function impairment and organ inflammation. Consequently, the main objective of this study was to elucidate DON and ZEN effects on the mRNA expression of pro-inflammatory cytokines and other immune related genes in the kidneys of piglets. METHODS: Fifteen 6-week-old piglets were randomly assigned to three dietary treatments for 4 weeks: control diet, and diets contaminated with either 8 mg DON/kg feed or 0.8 mg ZEN/kg feed. Kidney samples were collected after treatment, and RNA-seq was used to investigate the effects on immune-related genes and gene networks. RESULTS: A total of 186 differentially expressed genes (DEGs) were screened (120 upregulated and 66 downregulated). Gene ontology analysis revealed that the immune response, and cellular and metabolic processes were significantly controlled by these DEGs. The inflammatory stimulation might be an effect of the following enriched Kyoto encyclopedia of genes and genomes pathway analysis found related to immune and disease responses: cytokine-cytokine receptor interaction, chemokine signaling pathway, toll-like receptor signaling pathway, systemic lupus erythematosus (SLE), tuberculosis, Epstein-Barr virus infection, and chemical carcinogenesis. The effects of DON and ZEN on genome-wide expression were assessed, and it was found that the DEGs associated with inflammatory cytokines (interleukin 10 receptor, beta, chemokine [C-X-C motif] ligand 9, CXCL10, chemokine [C-C motif] ligand 4), proliferation (insulin like growth factor binding protein 4, IgG heavy chain, receptor-type tyrosine-protein phosphatase C, cytochrome P450 1A1, ATP-binding cassette sub-family 8), and other immune response networks (lysozyme, complement component 4 binding protein alpha, oligoadenylate synthetase 2, signaling lymphocytic activation molecule-9, α-aminoadipic semialdehyde dehydrogenase, Ig lambda chain c region, pyruvate dehydrogenase kinase, isozyme 4, carboxylesterase 1), were suppressed by DON and ZEN. CONCLUSION: In summary, our results indicate that high concentrations of DON and ZEN suppress the inflammatory response in kidneys, leading to potential effects on immune homeostasis.

Deoxynivalenol- and zearalenone-contaminated feeds alter gene expression profiles in the livers of piglets.

OBJECTIVE: The Fusarium mycotoxins of deoxynivalenol (DON) and zerolenone (ZEN) cause health hazards for both humans and farm animals. Therefore, the main intention of this study was to reveal DON and ZEN effects on the mRNA expression of pro-inflammatory cytokines and other immune related genes in the liver of piglets. METHODS: In the present study, 15 six-week-old piglets were randomly assigned to the following three different dietary treatments for 4 weeks: control diet, diet containing 8 mg DON/kg feed, and diet containing 0.8 mg ZEN/kg feed. After 4 weeks, liver samples were collected and sequenced using RNA-Seq to investigate the effects of the mycotoxins on genes and gene networks associated with the immune systems of the piglets. RESULTS: Our analysis identified a total of 249 differentially expressed genes (DEGs), which included 99 upregulated and 150 downregulated genes in both the DON and ZEN dietary treatment groups. After biological pathway analysis, the DEGs were determined to be significantly enriched in gene ontology terms associated with many biological pathways, including immune response and cellular and metabolic processes. Consistent with inflammatory stimulation due to the mycotoxin-contaminated diet, the following Kyoto encyclopedia of genes and genomes pathways, which were related to disease and immune responses, were found to be enriched in the DEGs: allograft rejection pathway, cell adhesion molecules, graft-versus-host disease, autoimmune thyroid disease (AITD), type I diabetes mellitus, human T-cell leukemia lymphoma virus infection, and viral carcinogenesis. Genome-wide expression analysis revealed that DON and ZEN treatments downregulated the expression of the majority of the DEGs that were associated with inflammatory cytokines (interleukin 10 receptor, beta, chemokine [C-X-C motif] ligand 9), proliferation (insulin-like growth factor 1, major facilitator superfamily domain containing 2A, insulin-like growth factor binding protein 2, lipase G, and salt inducible kinase 1), and other immune response networks (paired immunoglobulin-like type 2 receptor beta, Src-like-adaptor-1 [SLA1], SLA3, SLA5, SLA7, claudin 4, nicotinamide N-methyltransferase, thyrotropin-releasing hormone degrading enzyme, ubiquitin D, histone H2B type 1, and serum amyloid A). CONCLUSION: In summary, our results demonstrated that high concentrations DON and ZEN disrupt immune-related processes in the liver.

Identification of Susceptibility Loci and Genes for Colorectal Cancer Risk.

BACKGROUND & AIMS: Known genetic factors explain only a small fraction of genetic variation in colorectal cancer (CRC). We conducted a genome-wide association study to identify risk loci for CRC. METHODS: This discovery stage included 8027 cases and 22,577 controls of East-Asian ancestry. Promising variants were evaluated in studies including as many as 11,044 cases and 12,047 controls. Tumor-adjacent normal tissues from 188 patients were analyzed to evaluate correlations of risk variants with expression levels of nearby genes. Potential functionality of risk variants were evaluated using public genomic and epigenomic databases. RESULTS: We identified 4 loci associated with CRC risk; P values for the most significant variant in each locus ranged from 3.92 × 10(-8) to 1.24 × 10(-12): 6p21.1 (rs4711689), 8q23.3 (rs2450115, rs6469656), 10q24.3 (rs4919687), and 12p13.3 (rs11064437). We also identified 2 risk variants at loci previously associated with CRC: 10q25.2 (rs10506868) and 20q13.3 (rs6061231). These risk variants, conferring an approximate 10%-18% increase in risk per allele, are located either inside or near protein-coding genes that include transcription factor EB (lysosome biogenesis and autophagy), eukaryotic translation initiation factor 3, subunit H (initiation of translation), cytochrome P450, family 17, subfamily A, polypeptide 1 (steroidogenesis), splA/ryanodine receptor domain and SOCS box containing 2 (proteasome degradation), and ribosomal protein S2 (ribosome biogenesis). Gene expression analyses showed a significant association (P < .05) for rs4711689 with transcription factor EB, rs6469656 with eukaryotic translation initiation factor 3, subunit H, rs11064437 with splA/ryanodine receptor domain and SOCS box containing 2, and rs6061231 with ribosomal protein S2. CONCLUSIONS: We identified susceptibility loci and genes associated with CRC risk, linking CRC predisposition to steroid hormone, protein synthesis and degradation, and autophagy pathways and providing added insight into the mechanism of CRC pathogenesis.

Relationships between cognitive function and body composition among community-dwelling older adults: a cross-sectional study.

BACKGROUND: Previous studies reported mixed results regarding the association between cognition and body weight in late life. We evaluated the relationships between cognitive function and body composition among community-dwelling older adults. METHODS: Three hundred twenty subjects (≥65 years, women 53%) with available data of cognitive function and body composition from 2010 Hallym Aging Study. Cognitive function was assessed using Korean Mini-Mental State Examination (K-MMSE). Dual-energy X-ray absorptiometry (DEXA) was used for measuring body composition including body fat and lean body mass. Anthropometric measurements and laboratory data were collected in clinical examination. Body composition variables were divided into sex-specific tertiles, and examined by multivariable logistic regression. RESULTS: Among female, the highest tertile group of fat mass and second tertile group of total lean body mass were associated with lower risk for cognitive impairment compared to the respective first tertile groups (odds ratios, 0.23 and 0.09, respectively; 95% confidence intervals, 0.04-0.88 and 0.01-0.44, respectively) after adjusting for confounding factors. In male, higher arm bone mineral content was associated with lower risk for cognitive impairment, but significance was lost after adjusting for adiponectin, age, and education. CONCLUSIONS: Higher fat mass and lean body mass were associated with lower risk of cognitive impairment in older women. These observations suggest that body fat and lean mass later in life might be beneficial for cognition.

High Endogenous Accumulation of ω-3 Polyunsaturated Fatty Acids Protect against Ischemia-Reperfusion Renal Injury through AMPK-Mediated Autophagy in Fat-1 Mice.

Regulated autophagy is involved in the repair of renal ischemia-reperfusion injury (IRI). Fat-1 transgenic mice produce ω3-Polyunsaturated fatty acids (ω3-PUFAs) from ω6-Polyunsaturated fatty acids (ω6-PUFAs) without a dietary ω3-PUFAs supplement, leading to a high accumulation of omega-3 in various tissues. ω3-PUFAs show protective effects against various renal injuries and it has recently been reported that ω3-PUFAs regulate autophagy. We assessed whether ω3-PUFAs attenuated IR-induced acute kidney injury (AKI) and evaluated its associated mechanisms. C57Bl/6 background fat-1 mice and wild-type mice (wt) were divided into four groups: wt sham (n = 10), fat-1 sham (n = 10), wt IRI (reperfusion 35 min after clamping both the renal artery and vein; n = 15), and fat-1 IRI (n = 15). Kidneys and blood were harvested 24 h after IRI and renal histological and molecular data were collected. The kidneys of fat-1 mice showed better renal cell survival, renal function, and pathological damage than those of wt mice after IRI. In addition, fat-1 mice showed less oxidative stress and autophagy impairment; greater amounts of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II, Beclin-1, and Atg7; lower amounts of p62; and, higher levels of renal cathepsin D and ATP6E than wt kidneys. They also showed more adenosine monophosphate-activated protein kinase (AMPK) activation, which resulted in the inhibition of phosphorylation of the mammalian target of rapamycin (mTOR). Collectively, ω3-PUFAs in fat-1 mice contributed to AMPK mediated autophagy activation, leading to a renoprotective response.

Comprehensive identification of sexually dimorphic genes in diverse cattle tissues using RNA-seq.

BACKGROUND: Molecular mechanisms associated with sexual dimorphism in cattle have not been well elucidated. Furthermore, as recent studies have implied that gene expression patterns are highly tissue specific, it is essential to investigate gene expression in a variety of tissues using RNA-seq. Here, we employed and compared two statistical methods, a simple two group test and Analysis of deviance (ANODEV), in order to investigate bovine sexually dimorphic genes in 40 RNA-seq samples distributed across two factors: sex and tissue. RESULTS: As a result, we detected 752 sexually dimorphic genes across tissues from two statistical approaches and identified strong tissue-specific patterns of gene expression. Additionally, significantly detected sex-related genes shared between two mammal species (cattle and rat) were identified using qRT-PCR. CONCLUSIONS: Results of our analyses reveal that sexual dimorphism of metabolic tissues and pituitary gland in cattle involves various biological processes. Several differentially expressed genes between sexes in cattle and rat species are shared, but show tissue-specific patterns. Finally, we concluded that two distinct statistical approaches have their advantages and disadvantages in RNA-seq studies investigating multiple tissues.

Co-inhibition of Angiotensin II Receptor and Endothelin-1 Attenuates Renal Injury in Unilateral Ureteral Obstructed Mice.

BACKGROUND/AIMS: Both endothelin-1 (ET-1) and the renin-angiotensin system (RAS) may play important roles in renal fibrosis in the obstructed kidney. However, there have been few clear demonstrations of a relationship between their activation and additive or synergistic roles in renal fibrosis. We investigated the protective roles and relationship between renal RAS and ET-1 in unilateral ureteral obstruction (UUO) mice. METHODS: 8-week-old male C57BL/6 mice were divided into seven groups: sham, bosentan+sham, valsartan+sham, vehicle+UUO, bosentan+UUO, valsartan+UUO, and valsartan+bosentan+UUO. Valsartan and bosentan were administered orally using an NG tube (valsartan 10 mg/kg/day, bosentan 100 mg/kg/day for 8 days, after which the molecular and structural kidney parameters were evaluated. Bosentan treatment elevated plasma renin activity, renal renin, and AT1R expression in UUO mice. RESULTS: Although valsartan decreased plasma ET-1 in these mice, it did not affect ET(A) or ET(B) in their kidneys. Co-treatment with valsartan and bosentan decreased ET-1 in these mice compared to the single treatments. Bosentan, but not valsartan, elevated eNOS expression in their kidneys. Co-treatment with valsartan and bosentan reduced TGF-ß, α-SMA, and collagen IV expression, and the Masson's trichrome stained area in their kidneys. CONCLUSIONS: Bosentan and valsartan acted complementarily, and co-treatment with both drugs had an additive protective effect against renal fibrosis.

Gender Differences in Sleep Disturbance among Elderly Koreans: Hallym Aging Study.

Sleep is an important component in our lives as it is necessary throughout one's entire life span. This study was conducted to elucidate whether there are gender differences in sleep quality and what factors can affect sleep quality in community-dwelling elderly Koreans. A total of 382 subjects (175 males and 207 females) were recruited among elderly aged 45 or over who participated in the 2010 Hallym Aging Study (HAS). They were invited to a general hospital and were evaluated for socioeconomic status, smoking history, and various clinical measures. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI). A higher score indicates poorer subjective sleep quality, (PSQI global score > 5 suggests sleep disturbance). After adjusting for potential covariates, our results show that alcohol increases the odds for poor sleep (odds ratio [OR] = 3.35, 95% confidence interval [CI] = 1.11-10.10) in males. In females, lack of exercise was the major risk factor of poor sleep as they are 4.46 times more likely to suffer from low sleep quality than those who exercise regularly (95% CI=1.56-13.75). Stress was also a risk factor for poor sleep. It was 5.60 times higher in the "always have stress" group than the "do not have stress" group (95% CI = 1.54-20.34). Thus, alcohol consumption is associated with men's sleep quality, while exercise and stress level affect women's.

Surgical treatment of lesions of the long head of the biceps brachii tendon with rotator cuff tear: a prospective randomized clinical trial comparing the clinical results of tenotomy and tenodesis.

BACKGROUND: Tenotomy and tenodesis are common treatments for lesions in the long head of biceps tendon (LHBT); however, which treatment is superior is still controversial. This study compared the outcomes of tenotomy with outcomes of tenodesis for treatment of LHBT lesions with rotator cuff tears. METHODS: The study enrolled 128 patients with LHBT lesions and small- to medium-sized rotator cuff tear. Arthroscopic LHBT tenotomy was done in 56 patients (group I), and LHBT tenodesis was done for 72 patients (group II) with rotator cuff repair. American Shoulder and Elbow Surgeons Score, simple shoulder test, pain visual analog scale, range of motion, and cosmetic changes were assessed initially, at 3, 6, and 12 months postoperatively, and the last visit. The elbow motor power and magnetic resonance imaging were evaluated at 12 months. RESULTS: Both groups showed improvement in functional scores after treatments, but no significant difference was found between the 2 groups at each assessment. The rate of Popeye deformity was 3 times higher in group I (P = .04). Group II showed greater forearm supination power than group I (P = .02). On magnetic resonance imaging, 45 patients (80.4%) in group I showed maintenance of the LHBT cut end within the bicipital groove, whereas 65 patients (90.3%) in group II showed maintenance of fixated LHBT. CONCLUSION: For the treatment of LHBT lesions with rotator cuff tear, patients with tenotomy and tenodesis both showed significant improvements in functional scores. The incidence of Popeye deformity was about 3-times higher in tenotomy group. No significant differences in elbow motor power were observed except greater forearm supination power in the tenodesis group.

Characterizing Milk Production Related Genes in Holstein Using RNA-seq.

Although the chemical, physical, and nutritional properties of bovine milk have been extensively studied, only a few studies have attempted to characterize milk-synthesizing genes using RNA-seq data. RNA-seq data was collected from 21 Holstein samples, along with group information about milk production ability; milk yield; and protein, fat, and solid contents. Meta-analysis was employed in order to generally characterize genes related to milk production. In addition, we attempted to investigate the relationship between milk related traits, parity, and lactation period. We observed that milk fat is highly correlated with lactation period; this result indicates that this effect should be considered in the model in order to accurately detect milk production related genes. By employing our developed model, 271 genes were significantly (false discovery rate [FDR] adjusted p-value<0.1) detected as milk production related differentially expressed genes. Of these genes, five (albumin, nitric oxide synthase 3, RNA-binding region (RNP1, RRM) containing 3, secreted and transmembrane 1, and serine palmitoyltransferase, small subunit B) were technically validated using quantitative real-time polymerase chain reaction (qRT-PCR) in order to check the accuracy of RNA-seq analysis. Finally, 83 gene ontology biological processes including several blood vessel and mammary gland development related terms, were significantly detected using DAVID gene-set enrichment analysis. From these results, we observed that detected milk production related genes are highly enriched in the circulation system process and mammary gland related biological functions. In addition, we observed that detected genes including caveolin 1, mammary serum amyloid A3.2, lingual antimicrobial peptide, cathelicidin 4 (CATHL4), cathelicidin 6 (CATHL6) have been reported in other species as milk production related gene. For this reason, we concluded that our detected 271 genes would be strong candidates for determining milk production.