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BACKGROUND: Hyperuricemia could be a risk for various chronic diseases, and it could be largely corrected by diet control. This study was a nationwide cross-sectional study to investigate the association between serum uric acid level and dietary fiber intake. METHODS: This study analyzed data based on the Korean National Health and Nutrition Examination Survey conducted from 2016 to 2018. Adults over 20 years of age with normal renal function, defined as an estimated glomerular filtration rate (eGFR) over 30mL/min/1.73m2, were included. The criteria for hyperuricemia were ≥ 7 mg/dL in men and ≥ 6 mg/dL in women. Data regarding dietary intake were obtained using the 24-hour recall method. RESULTS: A total of 15,278 subjects (6,455 males/8,823 females) were analyzed. The prevalence of hyperuricemia was 19.3% in men and 6.8% in women. There were significant, negative associations between serum uric acid and total fiber intake in both men and women. Consuming more than 27.9 g of dietary fiber in men and 20.7 g in women reduced the risk of hyperuricemia by approximately 30% with odds ratios of 0.72 (0.62-0.83) and 0.71 (0.56-0.88) in men and women, respectively. With regard to the risk reduction by the type of dietary fiber, cereal fiber was significantly identified in both men and women, while fruit fiber was only significant in men. In the subgroup analysis, this association remained significantly in young and metabolically healthy populations with normal weight. CONCLUSIONS: Dietary fiber intake was inversely associated with serum uric acid levels. This relationship was particularly significant in metabolically healthy young adults.
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BACKGROUND: Restrictions on daily life and changes in economic structure due to coronavirus disease 2019 (COVID-19) likely would have affected men and women differently. However, there is still a lack of research on the difference between men and women in the amount of change in depression during COVID-19 compared to before COVID-19. Therefore, the researchers investigated gender differences in the magnitude of increase in the prevalence of depression with its severity and individual symptoms during COVID-19 compared with pre-pandemic levels. METHODS: The Korea National Health and Nutrition Examination Survey (KNHANES) 2016 and 2018 were used to assess depression levels pre-pandemic and the KNHANES 2020 for pandemic depression levels. Depression was evaluated using the Patient Health Questionnaire-9 (PHQ-9). To analyze the differences between men and women in the magnitude of the mental health impact of COVID-19, the researchers analyzed the weighted differences in depression prevalence, severity, and individual symptoms during the COVID-19 pandemic compared to before COVID-19 stratified by gender. RESULTS: In men, there were significant increases in weighted prevalence for depression (1.2% percentage point; 95% confidence interval [CI], 0.0-2.3) and severe symptoms of depression (2.6-fold; 95% CI, 1.2-5.7). Among the individual symptoms of depression, significant increases during the pandemic compared to before were: little interest or pleasure in doing things, 1.26-fold; feeling tired or having little energy, 2.2-fold; and suicidal thoughts, 1.7-fold. However, there was no significant difference in prevalence, symptoms severity, and any symptom before and during COVID-19 in women. CONCLUSIONS: Because the pandemic is likely to increase mental problems of the affected over time due to such problems as financial stress and joblessness or post-infection health issues, the researchers anticipate an increase in the prevalence of some mental illnesses. In particular, since the suicide rate of men is higher than that of women, from a public health perspective, active interventions are needed to prevent an increase in the suicide rate due to COVID-19. It is also necessary to establish national policies to overcome the psychological, social, and economic losses resulting from COVID-19.
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COVID-19 , Masculino , Humanos , Femenino , COVID-19/epidemiología , Pandemias , Depresión/etiología , SARS-CoV-2 , Encuestas Nutricionales , Factores Sexuales , Ansiedad/epidemiologíaRESUMEN
BACKGROUND: It remains unclear whether a combination of glycemic variability and glycated hemoglobin (HbA1c) status leads to a higher incidence of cardiovascular disease (CVD). Therefore, to investigate CVD risk according to the glucose control status during early diabetes, we examined visit-to-visit HbA1c variability among patients with type 2 diabetes (T2DM). METHODS: In this 9-year retrospective study, we measured HbA1c levels at each visit and tracked the change in HbA1c levels for 3 years after the first presentation (observation window) in newly diagnosed T2DM patients. We later assessed the occurrence of CVD in the last 3 years (target outcome window) of the study period after allowing a 3-year buffering window. The HbA1c variability score (HVS; divided into quartiles, HVS_Q1-4) was used to determine visit-to-visit HbA1c variability. RESULTS: Among 4,817 enrolled T2DM patients, the mean HbA1c level was < 7% for the first 3 years. The group with the lowest HVS had the lowest rate of CVD (9.4%; 104/1,109 patients). The highest incidence of CVD of 26.7% (8/30 patients) was found in HVS [≥ 9.0%]_Q3, which was significantly higher than that in HVS [6.0-6.9%]_Q1 (P = 0.006), HVS [6.0-6.9%]_Q2 (P = 0.013), HVS [6.0-6.9%]_Q3 (P = 0.018), and HVS [7.0-7.9%]_Q3 (P = 0.040). CONCLUSION: To our knowledge, this is the first long-term study to analyze the importance of both HbA1c change and visit-to-visit HbA1c variability during outpatient visits within the first 3 years. Lowering glucose levels during early diabetes may be more critical than reducing visit-to-visit HbA1c variability.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Hemoglobina Glucada , Humanos , Glucemia , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/etiología , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Hemoglobina Glucada/análisis , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: We evaluated patients visiting a tertiary university hospital due to a diagnosis of diabetes with a goal of achieving blood glucose control and evaluated blood glucose persistence over 7 years according to the change in blood glucose evident at 3 months after the first visit. METHODS: Patients treated from 2009 to 2013 were categorized into four groups according to the change in HbA1c levels during the first 3 months of follow-up (Best_group, ≥ 1.6% decrease; Better_group, 0.5-1.5% decrease; Neutral_group, maintained at -0.4% to +0.4%; Worse_group, ≥ 0.5% increase). Each patient's blood glucose control status was then monitored for 7 years. The incidence of stroke and acute coronary syndrome during this period was confirmed. RESULTS: Overall, 9,776 patients were included. HbA1c values were lower in the Best_group than in the other groups at all time points (all P < 0.001). The rate of reaching targets of < 6.5% or < 7.0% HbA1c decreased over time; the rate at which the estimated glomerular filtration rate decreased to < 30 or < 60 mL/min/1.73m² increased over time (all trends, P < 0.01). CONCLUSION: Blood glucose control status in the first 3 months after initiating hospital care enabled estimation of the patient's glycemic control status for the next 7 years. In cases with poor initial blood glucose control, a new or more active method of blood glucose control should be sought.
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Glucemia , Diabetes Mellitus Tipo 2 , Diabetes Mellitus Tipo 2/diagnóstico , Hemoglobina Glucada/análisis , Control Glucémico , Hospitales , HumanosRESUMEN
BACKGROUND: In the euthyroid state, the risk of developing diabetes according to changes in thyroid-stimulating hormone (TSH) levels remains controversial. Additionally, the correlation of various body indices affecting blood glucose levels according to changes in TSH levels over a certain period is not well known. METHODS: Patients who underwent health check-ups twice at a 2 year interval at a tertiary university hospital between 2009 and 2018 were included. By dividing baseline TSH levels into quartiles (TSH_Q1, Q2, Q3, and Q4), various variables were compared, and their changes after 2 years (∆TSH_Q1, Q2, Q3, and Q4) were confirmed. RESULTS: Among 15 557 patients, the incidence of diabetes mellitus after 2 years was 2.4% (377/15 557 patients). There was no statistically significant difference in the incidence of diabetes according to TSH_Q (p = 0.243) or ∆TSH_Q (p = 0.131). However, as TSH levels increased, skeletal muscle mass decreased (p < 0.001), and body fat mass and percent body fat significantly increased (p < 0.001). As ∆TSH increased, ∆fasting blood glucose and ∆body mass index also significantly increased (all p < 0.001). The incidence of diabetes decreased significantly as skeletal muscle mass increased (odds ratio 0.734, p < 0.001). CONCLUSIONS: Owing to the short study period, it was not possible to prove a statistical relationship between the incidence of diabetes mellitus and TSH levels in the euthyroid state. Significant decreases in skeletal muscle mass and increases in body mass index and body fat mass according to baseline TSH levels were demonstrated. Therefore, a focus on improving physical functions, such as increasing muscle mass and decreasing fat, is required in this case.
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Glucemia , Tirotropina , Composición Corporal , Índice de Masa Corporal , Humanos , Estudios RetrospectivosRESUMEN
BACKGROUND: Diabetic nephropathy (DN) is one of the most important medical complications of diabetes mellitus. Autophagy is an important mediator of pathological response and plays a critical role in inflammation during the progression of diabetic nephropathy. Interleukin (IL)-17A favorably modulates inflammatory disorders including DN. In this study, we examined whether IL-17A deficiency affected the autophagy process in the kidneys of mice with streptozotocin (STZ)-induced DN. METHODS: The autophagic response of IL-17A to STZ-induced nephrotoxicity was evaluated by analyzing STZ-induced functional and histological renal injury in IL-17A knockout (KO) mice. RESULTS: IL-17A KO STZ-treated mice developed more severe nephropathy than STZ-treated wild-type (WT) mice, with increased glomerular damage and renal interstitial fibrosis at 12 weeks. IL-17A deficiency also increased the up-regulation of proinflammatory cytokines and fibrotic gene expression after STZ treatment. Meanwhile, autophagy-associated proteins were induced in STZ-treated WT mice. However, IL-17A KO STZ-treated mice displayed a significant decrease in protein expression. Especially, the levels of LC3 and ATG7, which play crucial roles in autophagosome formation, were notably decreased in the IL-17A KO STZ-treated mice compared with their WT counterparts. CONCLUSIONS: IL-17 deficiency aggravates of STZ-induced DN via attenuation of autophagic response. Our study demonstrated that IL-17A mediates STZ-induced renal damage and represents a potential therapeutic target in DN.
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Autofagosomas/inmunología , Citocinas/inmunología , Diabetes Mellitus Experimental/inmunología , Nefropatías Diabéticas/inmunología , Animales , Proteína 7 Relacionada con la Autofagia/metabolismo , Proteínas Relacionadas con la Autofagia/metabolismo , Línea Celular , Citocinas/genética , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Nefropatías Diabéticas/inducido químicamente , Nefropatías Diabéticas/patología , Humanos , Riñón/inmunología , Riñón/metabolismo , Riñón/patología , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas Asociadas a Microtúbulos/metabolismo , Factor de Transcripción STAT3/metabolismo , Estreptozocina , Enzimas Ubiquitina-Conjugadoras/metabolismoRESUMEN
Benign prostatic hyperplasia (BPH) is a progressive pathological condition associated with proliferation of prostatic tissues, prostate enlargement, and lower-urinary tract symptoms. However, the mechanism underlying the pathogenesis of BPH is unclear. The aim of this study was to investigate the protective effects of a combination of Stauntonia hexaphylla and Cornus officinalis (SC extract) on a testosterone propionate (TP)-induced BPH model. The effect of SC extract was examined in a TP-induced human prostate adenocarcinoma cell line. Male Sprague-Dawley rats were randomly divided into 5 groups (n = 6) for in vivo experiments. To induce BPH, all rats, except those in the control group, were administered daily with subcutaneous injections of TP (5 mg/kg) and orally treated with appropriate phosphate buffered saline/drugs (finasteride/saw palmetto/SC extract) for 4 consecutive weeks. SC extract significantly downregulated the androgen receptor (AR), prostate specific antigen (PSA), and 5α-reductase type 2 in TP-induced BPH in vitro. In in vivo experiments, SC extract significantly reduced prostate weight, size, serum testosterone, and dihydrotestosterone (DHT) levels. Histologically, SC extract markedly recovered TP-induced abnormalities and reduced prostatic hyperplasia, thereby improving the histo-architecture of TP-induced BPH rats. SC extract also significantly downregulated AR and PSA expression, as assayed using immunoblotting. Immunostaining revealed that SC extract markedly reduced the 5α-reductase type 2 and significantly downregulated the expression of proliferating cell nuclear antigen. In addition, immunoblotting of B-cell lymphoma 2 (Bcl-2) family proteins indicated that SC extract significantly downregulated anti-apoptotic Bcl-2 and markedly upregulated pro-apoptotic B cell lymphoma-associated X (Bax) expression. Furthermore, SC treatment significantly decreased the Bcl-2/Bax ratio, indicating induced prostate cell apoptosis in TP-induced BPH rats. Thus, our findings demonstrated that SC extract protects against BPH by inhibiting 5α-reductase type 2 and inducing prostate cell apoptosis. Therefore, SC extract might be useful in the clinical treatment of BPH.
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Apoptosis/efectos de los fármacos , Colestenona 5 alfa-Reductasa/química , Extractos Vegetales/farmacología , Hiperplasia Prostática/prevención & control , Sustancias Protectoras/uso terapéutico , Inhibidores de 5-alfa-Reductasa/química , Inhibidores de 5-alfa-Reductasa/farmacología , Inhibidores de 5-alfa-Reductasa/uso terapéutico , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Colestenona 5 alfa-Reductasa/metabolismo , Cornus/química , Cornus/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Humanos , Masculino , Extractos Vegetales/química , Extractos Vegetales/uso terapéutico , Hojas de la Planta/química , Hojas de la Planta/metabolismo , Antígeno Prostático Específico/sangre , Hiperplasia Prostática/etiología , Sustancias Protectoras/farmacología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ranunculales/química , Ranunculales/metabolismo , Ratas , Ratas Sprague-Dawley , Propionato de Testosterona/efectos adversosRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Panax ginseng C.A. Mey. (Korean ginseng) has been widely used in traditional medicine to treat diabetes mellitus for thousands of years. It also plays a key role in health maintenance owing to its anti-oxidant and anti-fatigue properties, and is quite popular as a dietary supplement. AIM OF THE STUDY: This study was designed to offer a complementary and alternative medicine to manage the diabetic kidney disease (DKD), which causes long-term damage to the renal structure. We also investigated the regulation of the autophagy mechanism, which is the underlying the pathogenesis of DKD. MATERIALS AND METHODS: The effect of Korean red ginseng (KRG) on DKD was evaluated using human kidney proximal tubular cells and streptozotocin (STZ)-treated Sprague-Dawley rat models. In vitro experiments were conducted to evaluate the proteins related to fibrosis and autophagy. This was followed by in vivo experiments involving rats treated with single intraperitoneal administration of STZ (60 mg/kg) and then with KRG solution orally for 4 weeks. Proteins related to renal injury, fibrosis, and autophagy were determined by immunoblotting. Hematoxylin and eosin (H&E), Periodic acid-Schiff (PAS), Sirius red, and immunostaining were processed for histological studies. RESULTS: KRG diminished the levels of metabolic measurements and blood parameters. Western blotting showed a decreased expression of proteins, such as TGF-ß1, KIM1, and AGE, which are responsible for renal inflammation, injury, and fibrosis. Histological studies also supported these results and revealed that the KRG-treated groups recovered from renal injury and fibrosis. Furthermore, the autophagy marker, LC3, was upregulated, whereas p62 was downregulated. The levels of proteins related to the autophagy mechanism, such as ATG7, increased, while mammalian target of rapamycin (mTOR) decreased with the KRG treatment and exhibited accelerated autophagy compared to the STZ alone group. CONCLUSIONS: KRG can suppress renal inflammation, injury, and fibrosis by blocking TGF-ß1 activation and can induce cellular autophagy. Therefore, this study strongly suggests that KRG exhibits a renoprotective effect against the STZ-induced DKD.
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Antiinflamatorios/uso terapéutico , Diabetes Mellitus Experimental/tratamiento farmacológico , Nefropatías Diabéticas/tratamiento farmacológico , Hiperglucemia/tratamiento farmacológico , Panax , Extractos Vegetales/uso terapéutico , Sustancias Protectoras/uso terapéutico , Animales , Antiinflamatorios/farmacología , Autofagia/efectos de los fármacos , Línea Celular , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/patología , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/patología , Fibrosis , Humanos , Hiperglucemia/sangre , Hiperglucemia/complicaciones , Hiperglucemia/patología , Riñón/efectos de los fármacos , Riñón/patología , Masculino , Fitoterapia , Extractos Vegetales/farmacología , Sustancias Protectoras/farmacología , Ratas Sprague-DawleyRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Stauntonia hexaphylla (Lardizabalaceae, S. hexaphylla) is traditionally used as a folk remedy for alleviating fever and for its anti- inflammatory and analgesic properties. In Korea and China, S. hexaphylla has been used as a traditional medicine that acts as diuretic and analgesic. S. hexaphylla has also been reported to inhibit osteoporosis and aldose reductase activity. AIM OF THE STUDY: The study aimed to evaluate the therapeutic effects of an extract of S. hexaphylla on testosterone induced benign prostate hyperplasia (BPH) models and to observe its mechanism of action. MATERIALS AND METHODS: To induce a BPH model in vitro and in vivo, a testosterone-treated LNCaP cell line and Sprague Dawley (SD) rats were used, respectively. Androgen receptors (ARs) and prostate-specific antigens (PSA), which are typical BPH-related proteins, were evaluated using western blotting. Prostate weights and dihydrotestosterone (DHT) levels were measured in vivo, and histopathology of the prostate examined using hematoxylin and eosin staining. Proliferating cell nuclear antigen (PCNA) and 5α-reductase type 2 were also evaluated via immunohistochemistry (IHC). In addition, TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) staining and LC3 staining of IHC were performed to evaluate apoptosis and autophagy. RESULTS: S. hexaphylla reduced prostates weights and the thickness of prostate epithelial cells. In vivo and in vitro, PSA and ARs were downregulated following S. hexaphylla treatment. The S. hexaphylla extracts also reduced DHT and 5α-reductase type 2 expression. In addition, the expression of PCNA was reduced, and in the TUNEL staining and IHC of LC3, the number of positive cells was increased in the groups treated with S. hexaphylla. CONCLUSIONS: It was observed that extracts of S. hexaphylla inhibited both 5α -reductase type 2 and ARs. The results indicate that the use of S. hexaphylla extract in BPH is probably beneficial through 5α-reductase inhibition and α-adrenergic receptor blockade. In addition, apoptosis and autophagy were induced, and PCNA was downregulated after S. hexaphylla treatment. Therefore, it can be concluded that S. hexaphylla has a therapeutic effect on BPH.
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Extractos Vegetales/uso terapéutico , Hiperplasia Prostática/tratamiento farmacológico , Ranunculales , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Colestenona 5 alfa-Reductasa/metabolismo , Dihidrotestosterona/metabolismo , Humanos , Masculino , Extractos Vegetales/farmacología , Próstata/efectos de los fármacos , Próstata/metabolismo , Próstata/patología , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patología , Ratas Sprague-Dawley , Receptores Androgénicos/metabolismoRESUMEN
AIM: Growth arrest and DNA-damage-inducible 45 beta (GADD45ß) is a member of the gene family associated with cell growth control, apoptosis, and DNA damage repair. The aim of present study was to determine the potential effects of GADD45ß deletion on prostate hyperplasia progression. MAIN METHODS: LNCaP cells were incubated with testosterone propionate (1⯵M) for 48â¯h and specific siRNA used to suppress GADD45ß expression in vitro. For in vivo experiments, testosterone (3â¯mg/kg, IP) was injected into wild-type (WT) and GADD45ß knockout (GADD45ß-/-) C57BL/6J mice for 21 consecutive days, and serum and prostate tissues subjected to biological and histochemical analyses. KEY FINDINGS: GADD45ß-silenced LNCaP cells showed suppressed testosterone-induced 5α-reductase 2 and androgen receptor expression compared to control LNCaP cells. Moreover, after 21â¯days of testosterone treatment, prostate weight and stromal tissue increment were relatively lower in GADD45ß-/- than WT counterpart mice. Inhibition of testosterone-induced 5α-reductase 2 and proliferating cell nuclear antigen expression in the GADD45ß-/- group was confirmed via immunohistochemistry analyses. SIGNIFICANCE: Although the exact correlation between GADD45ß and prostate hyperplasia remains to be established, the present GADD45ßdeletion suppressed testosterone-induced prostate hyperplasia which was accompanied by inhibition of 5α-reductase 2-related protein expression.
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Antígenos de Diferenciación/metabolismo , Antígenos de Diferenciación/fisiología , Apoptosis/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Hiperplasia Prostática/prevención & control , Neoplasias de la Próstata/prevención & control , Testosterona/toxicidad , Andrógenos/toxicidad , Animales , Antígenos de Diferenciación/genética , Proliferación Celular/efectos de los fármacos , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Hiperplasia Prostática/inducido químicamente , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patología , Neoplasias de la Próstata/inducido químicamente , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Células Tumorales CultivadasRESUMEN
Background: Colistin (polymyxin E) is an important constituent of the polymyxin class of cationic polypeptide antibiotics. Intrarenal oxidative stress can contribute to colistin-induced nephrotoxicity. Nicotinamide adenine dinucleotide 3-phosphate oxidases (Noxs) are important sources of reactive oxygen species. Among the various types of Noxs, Nox4 is predominantly expressed in the kidney. Objectives: We investigated the role of Nox4 and benefit of Nox4 inhibition in colistin-induced acute kidney injury using in vivo and in vitro models. Methods: Human proximal tubular epithelial (HK-2) cells were treated with colistin with or without NOX4 knockdown, or GKT137831 (most specific Nox1/4 inhibitor). Effects of Nox4 inhibition on colistin-induced acute kidney injury model in Sprague-Dawley rats were examined. Results: Nox4 expression in HK-2 cells significantly increased following colistin exposure. SB4315432 (transforming growth factor-ß1 receptor I inhibitor) significantly inhibited Nox4 expression in HK-2 cells. Knockdown of NOX4 transcription reduced reactive oxygen species production, lowered the levels of pro-inflammatory markers (notably mitogen-activated protein kinases) implicated in colistin-induced nephrotoxicity and attenuated apoptosis by altering Bax and caspase 3/7 activity. Pretreatment with GKT137831 replicated these effects mediated by downregulation of mitogen-activated protein kinase activities. In a rat colistin-induced acute kidney injury model, administration of GKT137831 resulted in attenuated colistin-induced acute kidney injury as indicated by attenuated impairment of glomerulus function, preserved renal structures, reduced expression of 8-hydroxyguanosine and fewer apoptotic cells. Conclusions: Collectively, these findings identify Nox4 as a key source of reactive oxygen species responsible for kidney injury in colistin-induced nephrotoxicity and highlight a novel potential way to treat drug-related nephrotoxicity.
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Lesión Renal Aguda/inducido químicamente , Antibacterianos/efectos adversos , Colistina/efectos adversos , NADPH Oxidasa 4/metabolismo , Estrés Oxidativo , Factor de Crecimiento Transformador beta/metabolismo , Animales , Línea Celular , Modelos Animales de Enfermedad , Células Epiteliales/efectos de los fármacos , Células Epiteliales/fisiología , Humanos , Modelos Biológicos , Ratas Sprague-DawleyRESUMEN
The Mre11, Rad50, and Nbs1 (MRN) complex is a DNA double-strand break sensor involved in DNA damage repair. Herein, we explored whether deletion of NAD(P)H: quinone oxidoreductase 1 (NQO1), a cytoprotective gene, affected MRN complex expression in the kidney after cisplatin-induced acute kidney injury (AKI). In vitro, cisplatin increased the expression of MRN complex proteins and NQO1 in NQO1-expressing ACHN cells in a time- and concentration-dependent manner. The expression of MRN complex proteins was relatively inhibited in NQO1-knockdown cells. In vivo, increased expression of renal MRN complex proteins was accompanied by upregulation of γ-H2A histone member X, a DNA damage marker, in cisplatin-treated wild-type mice. Although the NQO1-knockout (NQO1(-/-)) mice showed more severe cisplatin-induced renal damage, the renal expression of MRN complex proteins was lower than in NQO1-expressing mice; expression of poly[ADP-ribose] polymerase 1, which promotes MRN complex accumulation, was also lower in these animals. In addition, cisplatin-induced expression of DNA damage repair-related proteins, ataxia telangiectasia mutated and sirtuin1, markedly decreased in the NQO1(-/-) group, relative to the NQO1-expressing mice. These findings suggest that NQO1 deletion might be associated with decreased MRN complex expression, which might be partially responsible for the exacerbation of cisplatin-induced AKI in the absence of NQO1.
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Lesión Renal Aguda/patología , Cisplatino/toxicidad , Represión Epigenética , Eliminación de Gen , NAD(P)H Deshidrogenasa (Quinona)/genética , Transportadoras de Casetes de Unión a ATP/genética , Transportadoras de Casetes de Unión a ATP/metabolismo , Ácido Anhídrido Hidrolasas , Lesión Renal Aguda/inducido químicamente , Animales , Proteínas de la Ataxia Telangiectasia Mutada/genética , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Daño del ADN/efectos de los fármacos , Reparación del ADN , Enzimas Reparadoras del ADN/genética , Enzimas Reparadoras del ADN/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Regulación de la Expresión Génica , Silenciador del Gen , Humanos , Proteína Homóloga de MRE11 , Masculino , Ratones , Ratones Endogámicos C57BL , NAD(P)H Deshidrogenasa (Quinona)/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Sirtuina 1/genética , Sirtuina 1/metabolismoRESUMEN
BACKGROUND: To determine whether performing transient occlusion of uterine arteries (TOUA) immediately before laparoscopic myomectomy can reduce intraoperative complications. SUBJECTS AND METHODS: In a retrospective case-control study, laparoscopic myomectomy with and without TOUA was examined. Data were analyzed from 89 laparoscopic myomectomies performed by a single surgeon (Y.-S. Kwon) at Ulsan University Hospital (Ulsan, Korea) between March 2011 and December 2011. Surgical outcomes included preoperative myoma size, number of myoma, operative time, and operative blood loss. RESULTS: Forty-nine women underwent laparoscopic myomectomy with TOUA with endoscopic vascular clipping, whereas 40 control patients underwent laparoscopic myomectomy alone. The TOUA group had no case of nerve or vascular injury during the operation time. The mean time of occlusion of both the uterine arteries was 15 minutes. The TOUA group had less mean blood loss during the operation than the group with laparoscopic myomectomy alone (111.9 versus 203.4 mL; P<.001). There were no significant differences in size and number of uterine myomas and intraoperative complications between the two groups. Moreover, there was not even a single case of conversion of laparoscopy to laparotomy in either group. CONCLUSIONS: TOUA performed immediately before laparoscopic myomectomy facilitated minimally invasive surgery with lower blood loss and no differences in other intraoperative complications.
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Procedimientos Endovasculares , Complicaciones Intraoperatorias/prevención & control , Laparoscopía , Leiomioma/cirugía , Cuidados Preoperatorios/métodos , Arteria Uterina , Miomectomía Uterina/métodos , Neoplasias Uterinas/cirugía , Adulto , Estudios de Casos y Controles , Procedimientos Endovasculares/instrumentación , Femenino , Humanos , Estudios RetrospectivosRESUMEN
Benign prostatic hyperplasia (BPH) is characterized by hyperplasia of prostatic stromal and epithelial cells, which can lead to lower urinary tract symptoms. The prevalence of BPH increases in an age-dependent manner. We investigated the protective effect of ursolic acid in BPH development using a testosterone-induced BPH rat model. BPH was induced in experimental groups by daily subcutaneous injections of testosterone propionate (TP), for a period of four weeks. Ursolic acid was administrated daily by oral gavage at a dose level of 5mg/kg during the four weeks of TP injections. Animals were sacrificed on the scheduled termination, before prostates were weighed and subjected to histopathological examination. TP and dihydrotestosterone (DHT) levels in the serum and prostate were also measured. BPH-induced animals displayed an increase in prostate weight with increased testosterone and DHT levels in both the serum and prostate. However, ursolic acid treatment resulted in significant reductions in prostate weight and testosterone and DHT levels in both the serum and prostate, compared with BPH-induced animals. Histopathological examination also showed that ursolic acid treatment suppressed TP-induced prostatic hyperplasia. These findings indicate that ursolic acid may effectively inhibit the development of BPH and it may be a useful agent in BPH treatment.
Asunto(s)
Dihidrotestosterona/metabolismo , Modelos Animales de Enfermedad , Próstata/efectos de los fármacos , Hiperplasia Prostática/patología , Triterpenos/farmacología , Animales , Dihidrotestosterona/sangre , Masculino , Tamaño de los Órganos/efectos de los fármacos , Próstata/metabolismo , Antígeno Prostático Específico/sangre , Hiperplasia Prostática/metabolismo , Ratas , Ratas Wistar , Triterpenos/toxicidad , Ácido UrsólicoRESUMEN
The fruit of Cornus officinalis Sieb. et Zucc. is commonly prescribed in Asian countries as a tonic formula. In this study, the hepatoprotective effect of ethanolic extracts of the fruit of C. officinalis (ECO) was investigated in a mouse model of acetaminophen- (APAP-) induced liver injury. Pretreatment of mice with ECO (100, 250, and 500 mg/kg for 7 days) significantly prevented the APAP (200 mg/kg) induced hepatic damage as indicated by the serum marker enzymes (AST, ALT, and LDH). Parallel to these changes, ECO treatment also prevented APAP-induced oxidative stress in the mice liver by inhibiting lipid peroxidation (MDA) and restoring the levels of antioxidant enzymes (SOD, CAT, and HO-1) and glutathione. Liver injury and collagen accumulation were assessed using histological studies by hematoxylin and eosin staining. Our results indicate that ECO can prevent hepatic injuries associated with APAP-induced hepatotoxicity by preventing or alleviating oxidative stress.
RESUMEN
The fruits of Cudrania tricuspidata are a medicinal herb in Korea, known for its antiatherosclerotic and antiinflammatory effects. Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by the influx of lymphocytes into the dermis. Using an animal model of AD, we assessed whether C. tricuspidata suppresses the development of AD-like skin lesions. Cudrania tricuspidata was administered orally to NC/Nga mice with Dermatophagoides-farinae-induced AD-like lesions for 49 days. The effects of C. tricuspidata were assessed by measuring clinical symptoms, swelling of the skin on the back and ears, and plasma concentrations of mTARC (mouse thymus and activation regulated chemokine), histamine and immunoglobulin E (IgE). We found that C. tricuspidata (60 mg/kg/day) inhibited the development of AD-like skin lesions, reduced skin dermatitis scores and inhibited the histological changes induced by repeated application of D. farinae. In addition, C. tricuspidata inhibited the increases in plasma concentrations of mTARC, histamine and IgE induced by D. farinae. These findings indicate that C. tricuspidata inhibits the development of AD-like skin lesions induced by repeated applications of D. farinae in sensitized NC/Nga by suppressing plasma concentrations of mTARC, histamine and IgE.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Dermatitis Atópica/tratamiento farmacológico , Frutas/química , Moraceae/química , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Quimiocina CCL17/sangre , Dermatitis Atópica/parasitología , Dermatitis Atópica/patología , Dermatophagoides farinae/inmunología , Dermatophagoides farinae/patogenicidad , Evaluación Preclínica de Medicamentos , Histamina/sangre , Inmunoglobulina E/sangre , Masculino , Ratones , Estructura Molecular , Prednisolona/sangre , Índice de Severidad de la Enfermedad , Factores de TiempoRESUMEN
Despite ongoing intensive asthma research, the incidence of asthma is increasing worldwide. We investigated in this study the effects of Amomum compactum on ovalbumin (OVA)-induced asthma in a mouse model, and studied the possible mechanism for its anti-asthmatic action. Our data show that an A. compactum treatment markedly decreased the number of infiltrating eosinophils and the hypersecretion of mucus when compared with the effects on mice treated with OVA alone. The A. compactum treatment dose-dependently decreased the levels of reactive oxygen species (ROS) and T helper (Th)2 cytokines, including interleukin (IL)-4 and IL-5, in the bronchoalveolar lavage fluid (BALF), and a high dose of A. compactum effectively reduced the level of total immunoglobulin (Ig)E in the serum. Taken together, these data indicate that the administration of A. compactum may have potential therapeutic value when used as an adjuvant for the immunomodulatory treatment of allergic asthma.
Asunto(s)
Amomum/química , Asma/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Animales , Asma/inducido químicamente , Relación Dosis-Respuesta a Droga , Eosinófilos/efectos de los fármacos , Inmunoglobulina E/sangre , Factores Inmunológicos , Ratones , Moco/efectos de los fármacos , Moco/metabolismo , Ovalbúmina/efectos adversos , Fitoterapia , Plantas Medicinales , Especies Reactivas de Oxígeno/análisis , Células Th2/inmunologíaRESUMEN
Sanguisorba officinalis L. is known to have anti-inflammatory properties. However, the potential effects of S. officinalis against asthma have not been reported. In the present study, we investigated the protective effects and underlying mechanisms of S. officinalis in a murine ovalbumin (OVA)-induced asthma model. Mice were sensitized and challenged by OVA inhalation to induce airway inflammation and remodeling. S. officinalis ethanolic extract (SOEE) markedly decreased the number of infiltrated inflammatory cells, together with a reduction in the levels of T-helper type 2 cytokines and immunoglobulin E levels. Histopathological studies showed that inflammatory cell infiltration and mucus hypersecretion were inhibited by SOEE. In addition, OVA-induced increases in reactive oxygen species were attenuated by SOEE. All these effects were correlated with heme oxygenase-1 (HO-1) induction by SOEE. These results indicate that SOEE has therapeutic potential against bronchial asthma associated with allergic diseases that is due, at least in part, to HO-1 upregulation.
Asunto(s)
Antiasmáticos , Asma/metabolismo , Hemo-Oxigenasa 1/metabolismo , Extractos Vegetales , Sanguisorba/química , Regulación hacia Arriba/efectos de los fármacos , Análisis de Varianza , Animales , Antiasmáticos/farmacología , Antiasmáticos/uso terapéutico , Asma/inducido químicamente , Asma/tratamiento farmacológico , Líquido del Lavado Bronquioalveolar/química , Citocinas/metabolismo , Modelos Animales de Enfermedad , Femenino , Histocitoquímica , Inmunoglobulina E/metabolismo , Pulmón/metabolismo , Ratones , Ratones Endogámicos BALB C , Moco/metabolismo , Infiltración Neutrófila/efectos de los fármacos , Ovalbúmina/efectos adversos , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Raíces de Plantas/química , Eosinofilia Pulmonar/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
From the seeds of Pharbitis nil (Convolvulaceae), two new oleanene-type triterpene glycosides, pharbitosides A (1) and B (2), together with beta-sitosterol, beta-sitosterol glucoside (daucosterol), caffeic acid, and methyl caffeate were isolated. The structure of pharbitoside A (1) was elucidated to be queretaroic acid 3-O-alpha-L-rhamnopyranosyl-(1-->2)-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranoside (1). Pharbitoside B (2) is a 21alpha-hydroxyoleanolic acid saponin carrying the same sugar moiety as that of pharbitoside A (1).
Asunto(s)
Ipomoea nil/química , Saponinas/análisis , Semillas/química , Triterpenos/análisis , Conformación de Carbohidratos , Hidrólisis , Espectroscopía de Resonancia Magnética , Espectrometría de Masa Bombardeada por Átomos Veloces , Espectrofotometría InfrarrojaRESUMEN
A new norditerpene alkaloid named 8-O-methylhypaconine (1) was isolated along with twelve known alkaloids from the underground parts of an unknown species of Aconitum plant culti vated in Korea. Among the known alkaloids, two dianthramide glucosides, N-(2'-beta-glucopyra nosyl-5'-hydroxysalicyl)-5-hydroxyanthranilic acid methyl ester (2) and N-(2'-beta-glucopyranosyl-5'-hydroxysalicyl)-5-hydroxy-6-methoxyanthranilic acid methyl ester (3), were isolated from Aconitum plants for the first time. The structures were established on the basis of chemical and spectroscopic methods.