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1.
Mol Med ; 27(1): 25, 2021 03 10.
Artículo en Inglés | MEDLINE | ID: mdl-33691614

RESUMEN

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.


Asunto(s)
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/metabolismo
2.
J Antimicrob Chemother ; 73(4): 962-972, 2018 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-29329393

RESUMEN

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.


Asunto(s)
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-Dawley
3.
Analyst ; 143(17): 4017-4021, 2018 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-30091428

RESUMEN

The speciation of quaternary ammonium polybromides (QBr2n+1) was quantitatively determined by voltammetric tribromide titration on a Pt ultramicroelectrode (UME). The concentration of Br3- in a QBr2n+1-water mixed solution (QBr2n+1-WMS) was electrochemically estimated by measuring the steady state current associated with the electro-reduction of Br3- in a linear sweep voltammogram (LSV). The pBr3- titration curves of QBr2n+1-WMSs show 2-4 plateaus, each of which relates to the formation of QBr2n+1 from Br3- and Br2. The values of pBr3- at these plateaus can be regarded as corrected equilibrium constants of QBr2n+1, K'eq(n), which is Keq(n)/γ±, where γ± is a mean activity coefficient in QBr2n+1-WMS. Based on the estimated K'eq(n), fractional diagrams of QBr2n+1 were obtained, which gave information on QBr2n+1 speciation.

4.
Sci Data ; 11(1): 861, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39127738

RESUMEN

Responding to threats in the real world demands a sophisticated orchestration of freeze and flight behaviors dynamically modulated by the neural activity. While the medial prefrontal cortex-basolateral amygdala (mPFC-BLA) network is known to play a pivotal role in coordinating these responses, the mechanisms underlying its population dynamics remain vague. As traditional Pavlovian fear conditioning models fall short in encapsulating the breadth of natural escape behaviors, we introduce a novel dataset to bridge this gap, capturing the defensive strategies of mice against a spider robot in a natural-like environment. The adaptive escape behaviors and concurrent mPFC-BLA activity in eight mice were monitored using wireless local field potential (LFP) and video recordings, both individually and in groups. Our data offers a unique avenue to explore the neural dynamics that govern fear- and vigilance-induced threat responses in isolated and social contexts. Supplemented by detailed methodologies and validation, the dataset allows for the analysis of the transient neural oscillatory dynamics, with prospective implications for the fields of neuroscience, robotics, and artificial intelligence.


Asunto(s)
Reacción de Fuga , Miedo , Corteza Prefrontal , Animales , Ratones , Corteza Prefrontal/fisiología , Amígdala del Cerebelo/fisiología , Conducta Animal
5.
Soa Chongsonyon Chongsin Uihak ; 35(4): 230-242, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39380563

RESUMEN

Objectives: Depression and anxiety are emotional difficulties that are common among adolescents. Adolescents suffering from depression and anxiety can exhibit problems such as antisocial behavior, aggression, and academic slump. This study aimed to explore the factors influencing adolescents' depression and anxiety during the coronavirus disease 2019 (COVID-19) pandemic. Methods: This study examined the data from an online student health survey conducted by the Ministry of Education in 2022. The survey participants were 131194 students ranging from the first grade of middle school to the third grade of high school. The influence of each variable on depression and anxiety was examined. Results: Factors that predicted depression and anxiety were sex (female), grade level (higher), financial difficulties (existing or unknown), physical activity (higher), sleep time (shorter), media usage time (higher), family/friends relationship (worse), and change in the health status of family, friends, and oneself due to COVID-19 (worse). Conclusion: These results may help identify patterns of depression and anxiety among adolescents caused by COVID-19 and maximize the intervention effect.

6.
Artículo en Inglés | MEDLINE | ID: mdl-21869901

RESUMEN

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.

7.
Phytother Res ; 26(4): 594-9, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21972057

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 Tiempo
8.
Artículo en Inglés | MEDLINE | ID: mdl-35206634

RESUMEN

The 2014 Time-Use Survey of Statistics Korea revealed that office workers are increasingly spending more than eight hours at work. This study conducted an exposure assessment for office workers in Korea. Indoor and outdoor air pollutants were measured in offices. A self-administered questionnaire was employed to determine work information, indoor air quality (IAQ) awareness, and subjective symptoms for 328 workers. Indoor air concentrations for measured air pollutants were below IAQ guideline values. The average concentrations of target air pollutants did not show significant differences except for benzene, which had relatively a higher concentration in national industrial complexes. The indoor benzene, ethylbenzene, and acetaldehyde concentrations were higher in offices where workers were having dry eye, ophthalmitis, and headache symptoms. This study provides reference values to manage IAQ in offices, suggesting that if the benzene concentration exceeds 4.23 µg/m3 in offices, it could cause dry eye symptoms. Considering the increasing working hours for office workers and health effects, workers' exposure to indoor pollutants should be reduced. In addition, the IAQ was heavily influenced by outdoor air levels and various indoor sources. Therefore, in areas with relatively high air pollution, greater monitoring and management is required considering the influence of outdoor air quality.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire Interior , Contaminación del Aire , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , Contaminación del Aire Interior/análisis , Monitoreo del Ambiente , Humanos , Medición de Riesgo
9.
Nanoscale ; 14(23): 8271-8280, 2022 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-35586949

RESUMEN

For the development of optically encryptable smart glass that can control the molecular alignment of liquid crystals (LCs), an azobenzene-based reactive molecule (ARM) capable of trans-cis photoisomerization is newly designed and synthesized. Photo-triggered LC-commandable smart glasses are successfully constructed by the surface functionalization technique using 3-aminopropyltriethoxysilane (APTMS) coupling agent and an ARM. The surface functionalization with the ARM is verified by spectroscopic analysis and various observations including changes in the wettability and surface morphology. Using the ARM-treated substrate, the LC command cell which can effectively switch the molecular orientation of nematic LC (E7) by the irradiation of UV and visible light is demonstrated. The results of optical investigation demonstrate the directional correlation between light and photoisomerization, revealing the tilt mechanism of azobenzene units. The capability to control the molecular orientation of LCs remotely and selectively allows the development of remote-controllable and encryptable smart glasses.

10.
J Hematol Oncol ; 13(1): 127, 2020 09 24.
Artículo en Inglés | MEDLINE | ID: mdl-32972438

RESUMEN

The clinical impact of minimal residual disease detection at early time points or during follow-ups has been shown to accurately predict relapses among patients with lymphomas, mainly in follicular and diffuse large B cell lymphoma. The field of minimal residual disease testing in mantle cell lymphoma is still evolving but has great impact in determining the prognosis. Flow cytometry and polymerase chain reaction-based testing are most commonly used methods in practice; however, these methods are not sensitive enough to detect the dynamic changes that underline lymphoma progression. Newer methods using next-generation sequencing, such as ClonoSeq, are being incorporated in clinical trials. Other techniques under evolution include CAPP-seq and anchored multiplex polymerase chain reaction-based methods. This review article aims to provide a comprehensive update on the status of minimal residual disease detection and its prognostic effect in mantle cell patients. The role of circulating tumor DNA-based minimal residual disease detection in lymphomas is also discussed.


Asunto(s)
Linfoma de Células del Manto/patología , Biomarcadores de Tumor , Cromosomas Humanos Par 11/genética , Cromosomas Humanos Par 11/ultraestructura , Cromosomas Humanos Par 14/genética , Cromosomas Humanos Par 14/ultraestructura , Ciclina D1/genética , ADN de Neoplasias/sangre , Citometría de Flujo/métodos , Predicción , Reordenamiento Génico de Cadena Pesada de Linfocito B , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Biopsia Líquida , Linfoma de Células del Manto/diagnóstico , Linfoma de Células del Manto/genética , Linfoma de Células del Manto/terapia , Reacción en Cadena de la Polimerasa Multiplex , Neoplasia Residual , Pronóstico , Translocación Genética
11.
J Ethnopharmacol ; 254: 112693, 2020 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-32112899

RESUMEN

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.


Asunto(s)
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-Dawley
12.
PLoS One ; 15(8): e0236879, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32790676

RESUMEN

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.


Asunto(s)
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 adversos
13.
J Ethnopharmacol ; 250: 112446, 2020 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-31812646

RESUMEN

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.


Asunto(s)
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/metabolismo
14.
Sci Signal ; 12(567)2019 02 05.
Artículo en Inglés | MEDLINE | ID: mdl-30723172

RESUMEN

Mantle cell lymphoma (MCL) is an aggressive B cell lymphoma that is largely chemoresistant. Ibrutinib, a drug that inhibits Bruton's tyrosine kinase (BTK), has improved the overall survival of patients with MCL; however, resistance to ibrutinib has emerged as a decisive, negative factor in the prognosis of MCL. Adopting a more patient-centric therapeutic approach that incorporates applied genomics and interrogation of B cell signaling pathways may offer an alternative route to reach durable remission in patients with MCL. Although targeting genetic variants in MCL is not yet feasible in the clinical setting, the identification and targeting of increasingly active B cell signaling pathways may be a viable therapeutic strategy that may improve patient outcomes. Genome-editing tools and sequencing platforms could play dominant roles in patient-centric approaches of treatment in the future, potentially improving clinical outcomes for patients with MCL.


Asunto(s)
Linfocitos B/metabolismo , Linfoma de Células del Manto/tratamiento farmacológico , Pirazoles/uso terapéutico , Pirimidinas/uso terapéutico , Transducción de Señal/efectos de los fármacos , Adenina/análogos & derivados , Agammaglobulinemia Tirosina Quinasa/antagonistas & inhibidores , Agammaglobulinemia Tirosina Quinasa/metabolismo , Apoptosis/efectos de los fármacos , Humanos , Linfoma de Células del Manto/metabolismo , Linfoma de Células del Manto/patología , Modelos Biológicos , Piperidinas , Inhibidores de Proteínas Quinasas/uso terapéutico
15.
Life Sci ; 211: 74-80, 2018 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-30195037

RESUMEN

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 µM) for 48 h and specific siRNA used to suppress GADD45ß expression in vitro. For in vivo experiments, testosterone (3 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 21 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.


Asunto(s)
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 Cultivadas
16.
J Exp Clin Cancer Res ; 37(1): 150, 2018 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-30005678

RESUMEN

The natural history of mantle cell lymphoma (MCL) is a continuous process with the vicious cycle of remission and recurrence. Because MCL cells are most vulnerable before their exposure to therapeutic agents, front-line therapy could eliminate MCL cells at the first strike, reduce the chance for secondary resistance, and cause long-term remissions. If optimized, it could become an alternative to cure MCL. The key is the intensity of front-line therapy. Both the Nordic 2 and the MD Anderson Cancer Center HCVAD trials, with follow-up times greater than 10 years, achieved long-term survivals exceeding 10 years. But the Achilles heel in both trials were the severe toxicities, such as secondary malignancies including myelodysplastic syndromes /leukemia. Therefore, intensive therapies can act as a double-edged sword providing long term survival at the cost of severe toxicities. In our opinion, although intensive chemotherapy can cause detrimental side effects, it is indispensable given that we run the risk of sacrificing long-term survivals in these young and fit patients. We must seek for a powerful alternative at the front-line. Furthermore, minimal residual disease negativity should be the optimal therapeutic goal to achieve before and after autologous stem cell transplantation. Some novel therapeutic strategies have shown to improve outcomes, but it is not yet clear as to how these results translate in population. Of note, MCL patients need to be stratified at diagnosis and be provided with different intensities of front-line regimen. In this review, we discuss current strategies for the treatment of young patients with newly diagnosed MCL.


Asunto(s)
Linfoma de Células del Manto/terapia , Adulto , Anciano , Femenino , Humanos , Linfoma de Células del Manto/patología , Masculino , Persona de Mediana Edad
17.
Arch Pharm Res ; 30(6): 691-4, 2007 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-17679545

RESUMEN

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.


Asunto(s)
Aconitum/química , Alcaloides/química , Diterpenos/química , Alcaloides/aislamiento & purificación , Diterpenos/aislamiento & purificación , Corea (Geográfico) , Espectroscopía de Resonancia Magnética , Espectrometría de Masa por Ionización de Electrospray , Espectrofotometría Infrarroja
18.
Toxicol Lett ; 243: 22-30, 2016 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-26723870

RESUMEN

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.


Asunto(s)
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/metabolismo
20.
J Laparoendosc Adv Surg Tech A ; 23(8): 679-83, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23631666

RESUMEN

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.


Asunto(s)
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 Retrospectivos
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