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1.
Artículo en Inglés | MEDLINE | ID: mdl-39038321

RESUMEN

Background: The intrauterine device is the most commonly used female contraceptive device, but the related complications of intrauterine devices are also common. Sometimes, intrauterine devices can cause uterine perforation, migrating into the abdominal cavity or other organs. At the same time, the intrauterine device may break into several small segments, migrate to distant organs, and even cause misdiagnosis. Objective: This study assessed the role of laparoscopy in treating intrauterine device migration. Design: This was a retrospective study involving in a review of a single case. Setting: This study was conducted at Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University. Participants: This study focued on a single case acout a 64-year-old female patient presented with repeated painless gross hematuria. She had a history of placing an intrauterine device and "removed the intrauterine device" in a local hospital for 20 years. Interventions: Laparoscopic ureterectomy was chosen based on the specific findings from the computerized tomography scan and cystoscopy. Abdominal computerized tomography showed high-density foreign body under the abdominal wall, size 2.29×0.51 cm, showed signs of edema in the surrounding tissue, and it was connected to the bladder wall. High-density lesions in the urachus and urachus calculi were considered. Cystoscopy showed the bubble position on the top of the bladder was depressed, a dark foreign body seemed to be seen inside, and the local mucosa was congested. The urachus foreign body, the urachus stone, was considered. Results: Computerized tomography examination showed a high-density space-occupying lesion at the position of the bladder and urachus tube. Cystoscopy showed local congestion at the top of the bladder, like urachus and dark foreign bodies, and no obvious abnormality in other parts of the bladder. Laparoscopy showed the urachus position was congested and edema, with local adhesion of the greater omentum and foreign bodies. The foreign bodies and surrounding tissues were removed by laparoscopic ureterectomy. Pathology showed tubular tissue, metal and plastic foreign bodies, fibrous tissue proliferation, and chronic inflammatory cell infiltration around the foreign bodies. Conclusion: The intrauterine device is a common contraceptive tool, and intrauterine device rupture and migration are normal. Migration to rare locations can lead to misdiagnosis. It can be removed by endoscopy, and combined with imaging and pathological examination, a correct diagnosis can finally be obtained. The patients should be advised to undergo regular check-ups after the procedure. These cases may provide diagnostic reference for similar symptoms of intrauterine device migration.

2.
Environ Res ; 231(Pt 1): 116115, 2023 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-37178752

RESUMEN

Exosomes are small extracellular vesicles that can be derived from human cells such as mesenchymal stem cells (MSCs). The size of exosomes is at nano-scale range and owing to their biocompatibility and other characteristics, they have been promising candidates for delivery of bioactive compounds and genetic materials in disease therapy, especially cancer therapy. Gastric cancer (GC) is a leading cause of death among patients and this malignant disease affects gastrointestinal tract that its invasiveness and abnormal migration mediate poor prognosis of patients. Metastasis is an increasing challenge in GC and microRNAs (miRNAs) are potential regulators of metastasis and related molecular pathways, especially epithelial-to-mesenchymal transition (EMT). In the present study, our aim was to explore role of exosomes in miR-200a delivery for suppressing EMT-mediated GC metastasis. Exosomes were isolated from MSCs via size exclusion chromatography. The synthetic miR-200a mimics were transfected into exosomes via electroporation. AGS cell line exposed to TGF-ß for EMT induction and then, these cells cultured with miR-200a-loaded exosomes. The transwell assays performed to evaluate GC migration and expression levels of ZEB1, Snail1 and vimentin measured. Exosomes demonstrated loading efficiency of 5.92 ± 4.6%. The TGF-ß treatment transformed AGS cells into fibroblast-like cells expressing two stemness markers, CD44 (45.28%) and CD133 (50.79%) and stimulated EMT. Exosomes induced a 14.89-fold increase in miR-200a expression in AGS cells. Mechanistically, miR-200a enhances E-cadherin levels (P < 0.01), while it decreases expression levels of ß-catenin (P < 0.05), vimentin (P < 0.01), ZEB1 (P < 0.0001) and Snail1 (P < 0.01), leading to EMT inhibition in GC cells. This pre-clinical experiment introduces a new strategy for miR-200a delivery that is of importance for preventing migration and invasion of GC cells.


Asunto(s)
Exosomas , MicroARNs , Humanos , Transición Epitelial-Mesenquimal/genética , Factor de Crecimiento Transformador beta , Exosomas/metabolismo , Vimentina , Línea Celular Tumoral , MicroARNs/genética , MicroARNs/metabolismo , Proliferación Celular , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/genética , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/metabolismo
3.
J Biol Chem ; 297(2): 100929, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34216621

RESUMEN

The NAD+-dependent deacetylase Sirt1 has been implicated in the prevention of many age-related diseases, including cancer, type 2 diabetes, and cardiovascular disease. Resveratrol, a plant polyphenol, exhibits antiaging, antitumor, and vascular protection effects by activating Sirt1. However, the molecular mechanism of Sirt1 activation as induced by resveratrol remains unclear. By knockdown/rescue experiments, fluorometric Sirt1 activity assay, immunoprecipitation, and pull-down assays, we identify here that the tumor suppressor LKB1 (liver kinase B1) as a direct activator of Sirt1 elicited by resveratrol. Resveratrol promotes the binding between LKB1 and Sirt1, which we first reported, and this binding leads to LKB1-mediated phosphorylation of Sirt1 at three different serine residues in the C terminus of Sirt1. Mechanistically, LKB1-mediated phosphorylation increases intramolecular interactions in Sirt1, such as the binding of the C terminus to the deacetylase core domain, thereby eliminating DBC1 (Deleted in Breast Cancer 1, Sirt1 endogenous inhibitor) inhibition and promoting Sirt1-substrate interaction. Functionally, LKB1-dependent Sirt1 activation increases mitochondrial biogenesis and respiration through deacetylation and activation of the transcriptional coactivator PGC-1α. These results identify Sirt1 as a context-dependent target of LKB1 and suggest that a resveratrol-stimulated LKB1-Sirt1 pathway plays a vital role in mitochondrial metabolism, a key physiological process that contributes to numerous age-related diseases.


Asunto(s)
Resveratrol/farmacología , Sirtuina 1 , Acetilación/efectos de los fármacos , Humanos , Mitocondrias/metabolismo , Biogénesis de Organelos , Fosforilación/efectos de los fármacos , Transducción de Señal/efectos de los fármacos
4.
Technol Health Care ; 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38759033

RESUMEN

BACKGROUND: Ever since the GALAD (gender-age-Lens culinaris agglutinin-reactive alpha-fetoprotein-alpha-fetoprotein-des-gamma-carboxy prothrombin) logistic regression model was established to diagnose hepatocellular carcinoma (HCC), there has been no high-level evidence that evaluates and summarizes it. OBJECTIVE: This meta-analysis was performed to assess the diagnostic ability of the GALAD model. METHODS: The following databases were systematically searched for original diagnostic studies on HCC: PubMed, Embase, Medline, the Web of Science, Cochrane Library, China National Knowledge Infrastructure Wanfang (China), Wiper and the Chinese BioMedical Literature Database. After screening the search results according to our criteria, the Quality Assessment of Diagnostic Accuracy Studies 2 tool was used to evaluate the methodologic qualities, and statistical software were used to output the statistics. RESULTS: Ultimately, 10 studies were included and analyzed. The results revealed the pooled sensitivity and specificity of the GALAD model to be 0.86 (95% confidence interval [CI]: 0.82, 0.90) and 0.90 (95% CI: 0.87, 0.92), respectively, for all-stage HCC. The area under the curve (AUC) was 0.94. For early-stage HCC, the pooled sensitivity and specificity of the GALAD model were 0.83 (95% CI: 0.78, 0.87) and 0.81 (95% CI: 0.78, 0.83), respectively. The AUC was 0.90. CONCLUSION: This meta-analysis confirmed that the GALAD model has excellent diagnostic performance for early-stage and all-stage HCC and can maintain high sensitivity and specificity in early-stage HCC. Therefore, the GALAD model is qualified for screening early-stage canceration from chronic liver disease.

5.
Int Urol Nephrol ; 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38958853

RESUMEN

PURPOSE: This study compared the effects of calcium oxalate stones and uric acid stones on male sexual function. METHODS: We enrolled 100 patients with ureteral stones. According to the composition of the stones, they were divided into the calcium oxalate stone group and the uric acid stone group. All patients underwent ureteroscopic holmium laser lithotripsy. General data such as age, body mass index, course of disease, stone diameter, and degree of renal hydronephrosis were compared. Sperm parameters, including sperm density, sperm viability, and sperm deformity rate, as well as International Index of Erectile Function-5 questionnaire (IIEF-5) scores, and Quality of Life (QOL) scores, were measured and compared before and 6 weeks after the surgery. RESULTS: There were no statistically significant differences in general data and sperm parameters between the two groups before the surgery (P > 0.05). However, there were significantly lower IIEF scores but significantly higher QOL scores in the uric acid stone group. In the calcium oxalate stone group, there were no statistically significant differences in sperm parameters, IIEF score, and QOL score before and after the surgery (P > 0.05). In the uric acid stone group, there were no statistically significant differences in sperm parameters before and after surgery (P > 0.05), whereas there were significantly higher IIEF scores but significantly lower QOL scores after the surgery (P < 0.05). The prevalence of erectile dysfunction (ED) in the uric acid stone group was 38.18% (21/55), which was significantly higher compared to 20.00% (9/45) in the calcium oxalate stone group (P < 0.05). The multivariate binary logistic regression analysis showed that the independent risk factor related to ED was uric acid stones (odds ratio: 2.637, 95% confidence interval 1.040-6.689, P = 0.041). No statistically significant differences were found in sperm parameters between patients with and without ED. CONCLUSION: Compared with the calcium oxalate stone group, patients with uric acid stones had a higher prevalence of ED and poorer sexual performance.

6.
World J Gastroenterol ; 30(15): 2128-2142, 2024 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-38681988

RESUMEN

BACKGROUND: The prognosis for hepatocellular carcinoma (HCC) in the presence of cirrhosis is unfavourable, primarily attributable to the high incidence of recurrence. AIM: To develop a machine learning model for predicting early recurrence (ER) of post-hepatectomy HCC in patients with cirrhosis and to stratify patients' overall survival (OS) based on the predicted risk of recurrence. METHODS: In this retrospective study, 214 HCC patients with cirrhosis who underwent curative hepatectomy were examined. Radiomics feature selection was conducted using the least absolute shrinkage and selection operator and recursive feature elimination methods. Clinical-radiologic features were selected through univariate and multivariate logistic regression analyses. Five machine learning methods were used for model comparison, aiming to identify the optimal model. The model's performance was evaluated using the receiver operating characteristic curve [area under the curve (AUC)], calibration, and decision curve analysis. Additionally, the Kaplan-Meier (K-M) curve was used to evaluate the stratification effect of the model on patient OS. RESULTS: Within this study, the most effective predictive performance for ER of post-hepatectomy HCC in the background of cirrhosis was demonstrated by a model that integrated radiomics features and clinical-radiologic features. In the training cohort, this model attained an AUC of 0.844, while in the validation cohort, it achieved a value of 0.790. The K-M curves illustrated that the combined model not only facilitated risk stratification but also exhibited significant discriminatory ability concerning patients' OS. CONCLUSION: The combined model, integrating both radiomics and clinical-radiologic characteristics, exhibited excellent performance in HCC with cirrhosis. The K-M curves assessing OS revealed statistically significant differences.


Asunto(s)
Carcinoma Hepatocelular , Hepatectomía , Cirrosis Hepática , Neoplasias Hepáticas , Aprendizaje Automático , Recurrencia Local de Neoplasia , Tomografía Computarizada por Rayos X , Humanos , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Femenino , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/cirugía , Estudios Retrospectivos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Anciano , Tomografía Computarizada por Rayos X/métodos , Pronóstico , Valor Predictivo de las Pruebas , Curva ROC , Medición de Riesgo/métodos , Medición de Riesgo/estadística & datos numéricos , Estimación de Kaplan-Meier , Adulto , Hígado/diagnóstico por imagen , Hígado/patología , Hígado/cirugía , Factores de Riesgo , Radiómica
7.
Biomed Rep ; 19(4): 73, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37746591

RESUMEN

Fibrous dysplasia of bone (FDB) is a rare benign condition in which fibrous tissue replaces normal bone architecture. FDB rarely undergoes malignant transformation, but there are reports of locally aggressive fibrous dysplasia with cortical destruction and soft tissue extension. Diagnosis of FDB malignant transformation is not easy, especially in monostotic form, because of the overlap in imaging features of locally aggressive fibrous dysplasia and fibrous dysplasia with malignant transformation. The present case study reports a rare case of FDB in a 23-year-old man with polyostotic fibrous dysplasia arising in the left side of the pelvis and lower limb bones with partial transformation to fibrosarcoma. This study explored the multimodal imaging features of FDB malignant transformation, to achieve early detection and improve diagnostic accuracy of local FDB aggressiveness and its malignant transformation.

8.
Viruses ; 15(11)2023 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-38005819

RESUMEN

Influenza A virus (IAV) continues to pose a significant global health threat, causing severe respiratory infections that result in substantial annual morbidity and mortality. Recent research highlights the pivotal role of innate immunity, cell death, and inflammation in exacerbating the severity of respiratory viral diseases. One key molecule in this process is ZBP1, a well-recognized innate immune sensor for IAV infection. Upon activation, ZBP1 triggers the formation of a PANoptosome complex containing ASC, caspase-8, and RIPK3, among other molecules, leading to inflammatory cell death, PANoptosis, and NLRP3 inflammasome activation for the maturation of IL-1ß and IL-18. However, the role for other molecules in this process requires further evaluation. In this study, we investigated the role of MLKL in regulating IAV-induced cell death and NLRP3 inflammasome activation. Our data indicate IAV induced inflammatory cell death through the ZBP1-PANoptosome, where caspases and RIPKs serve as core components. However, IAV-induced lytic cell death was only partially dependent on RIPK3 at later timepoints and was fully independent of MLKL throughout all timepoints tested. Additionally, NLRP3 inflammasome activation was unaffected in MLKL-deficient cells, establishing that MLKL and MLKL-dependent necroptosis do not act upstream of NLRP3 inflammasome activation, IL-1ß maturation, and lytic cell death during IAV infection.


Asunto(s)
Virus de la Influenza A , Gripe Humana , Humanos , Apoptosis/fisiología , Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Virus de la Influenza A/metabolismo , Necroptosis , Muerte Celular , Proteínas Quinasas/metabolismo
9.
Science ; 380(6652): 1372-1380, 2023 06 30.
Artículo en Inglés | MEDLINE | ID: mdl-37384704

RESUMEN

Adenosine monophosphate-activated protein kinase (AMPK) activity is stimulated to promote metabolic adaptation upon energy stress. However, sustained metabolic stress may cause cell death. The mechanisms by which AMPK dictates cell death are not fully understood. We report that metabolic stress promoted receptor-interacting protein kinase 1 (RIPK1) activation mediated by TRAIL receptors, whereas AMPK inhibited RIPK1 by phosphorylation at Ser415 to suppress energy stress-induced cell death. Inhibiting pS415-RIPK1 by Ampk deficiency or RIPK1 S415A mutation promoted RIPK1 activation. Furthermore, genetic inactivation of RIPK1 protected against ischemic injury in myeloid Ampkα1-deficient mice. Our studies reveal that AMPK phosphorylation of RIPK1 represents a crucial metabolic checkpoint, which dictates cell fate response to metabolic stress, and highlight a previously unappreciated role for the AMPK-RIPK1 axis in integrating metabolism, cell death, and inflammation.


Asunto(s)
Proteínas Quinasas Activadas por AMP , Metabolismo Energético , Necroptosis , Proteína Serina-Treonina Quinasas de Interacción con Receptores , Estrés Fisiológico , Animales , Ratones , Proteínas Quinasas Activadas por AMP/genética , Proteínas Quinasas Activadas por AMP/metabolismo , Fosforilación , Proteína Serina-Treonina Quinasas de Interacción con Receptores/genética , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo , Inflamación/metabolismo , Isquemia/metabolismo
10.
BJU Int ; 110(8 Pt B): E362-7, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22900675

RESUMEN

OBJECTIVES: To evaluate the effect of plum juice on struvite calculus formation in vitro and to explore the effect of plum juice on urease-producing bacteria and urease activity. The compliance of available drugs is low for struvite calculus after surgical treatment and functional food may represent a good choice as an alternative therapy. MATERIALS AND METHODS: Antibacterial activity was assessed using a microdilution antimicrobial susceptibility test. Urease activity was determined by measuring ammonia production. Struvite crystals were induced by Proteus mirabilis in artificial urine with natural and pH-adjusted plum juice. The optical density (OD)(600) and pH of artificial urine were examined, as well the shape and weights of crystals. RESULTS: Natural plum juice showed an antibacterial effect on urease-producing bacteria, whereas the pH-adjusted juice did not. A concentration-dependent inhibition on urease activity was found for both natural and pH-adjusted juice. Natural plum juice at a high concentration of 0.5% showed an obvious inhibition on the increase of OD(600) and pH of the artificial urine, and crystal formation was prevented by up to or more than 8 h, depending on the concentration of juice. Crystal weight in the natural plum juice groups was decreased in a concentration-dependent manner. The pH-adjusted plum juice did not show any effect on OD(600) and pH, although the presence of juice changed the crystal habit, indicating that the juice slowed the growth rate of crystals. CONCLUSIONS: Natural plum juice at high and moderate concentrations prevented the formation of P. mirabilis-induced crystals for up to 8 h in artificial urine. Although pH-adjusted and low-concentration natural juice did not prevent the occurrence of crystals, both types of juice slowed their growth rate.


Asunto(s)
Bebidas , Cálculos/prevención & control , Compuestos de Magnesio , Fosfatos , Prunus , Cristalización , Klebsiella pneumoniae/enzimología , Pruebas de Sensibilidad Microbiana , Proteus mirabilis/enzimología , Pseudomonas aeruginosa/enzimología , Staphylococcus aureus/enzimología , Estruvita , Ureasa/biosíntesis
11.
Pathogens ; 11(12)2022 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-36558734

RESUMEN

Filoviruses are a group of single-stranded negative sense RNA viruses. The most well-known filoviruses that affect humans are ebolaviruses and marburgviruses. During infection, they can cause life-threatening symptoms such as inflammation, tissue damage, and hemorrhagic fever, with case fatality rates as high as 90%. The innate immune system is the first line of defense against pathogenic insults such as filoviruses. Pattern recognition receptors (PRRs), including toll-like receptors, retinoic acid-inducible gene-I-like receptors, C-type lectin receptors, AIM2-like receptors, and NOD-like receptors, detect pathogens and activate downstream signaling to induce the production of proinflammatory cytokines and interferons, alert the surrounding cells to the threat, and clear infected and damaged cells through innate immune cell death. However, filoviruses can modulate the host inflammatory response and innate immune cell death, causing an aberrant immune reaction. Here, we discuss how the innate immune system senses invading filoviruses and how these deadly pathogens interfere with the immune response. Furthermore, we highlight the experimental difficulties of studying filoviruses as well as the current state of filovirus-targeting therapeutics.

12.
World J Urol ; 29(6): 713-7, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21153828

RESUMEN

PURPOSE: To compare the efficacy and safety of Shockwave lithotripsy (SWL) for upper urinary tract stones of various locations in children. METHODS: Between 1997 and 2008, a total of 311 children (average age: 7.9 ± 4.4 years, ranged from 6 months to 16 years) with upper urinary tract stones were treated by SWL using Dornier Compact S lithotripter at our department. Of those patients, 196 had renal stones (pelvic, 53; upper and mid calices, 75; lower calices, 68) with an average size of 9.42 ± 7.1 mm, and 115 had ureteral stones (proximal, 53; mid, 16; distal, 46) with an average size of 7.38 ± 5.87 mm. RESULTS: Overall stone-free rates of renal stones and ureteral stones at 3 months were 95.8% and 94.8% with 83.5% and 79.5% of efficacy quotient (EQ), respectively. In renal stone groups, the EQ for renal pelvic stones was 89.2%, for middle and upper calyx stones was 92.5%, which was higher than 71.9% for lower calices stones. In ureteral stone groups, the 82.3% of EQ for proximal ureteral stones and 83.0% for distal ureteral stones were higher than 63.6% for middle ureteral stones. Patients with larger stones had significant higher re-treatment rate (P < 0.05) and lower EQ than small stone groups. No serious side effect happened in the study. CONCLUSIONS: SWL for both renal stones and ureteral stones in pediatric group have comparable efficacy and safety, except that stones in lower calices and middle ureters have lower EQ than those in other locations.


Asunto(s)
Litotricia , Cálculos Urinarios/terapia , Sistema Urinario , Adolescente , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Cálculos Renales/terapia , Litotricia/efectos adversos , Masculino , Estudios Retrospectivos , Resultado del Tratamiento , Cálculos Ureterales/terapia
13.
Urol Res ; 39(5): 339-43, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21249491

RESUMEN

A series of 5,248 urinary stones was analyzed by Fourier transform infrared spectroscopy between 1999 and 2008. This study evaluated the percentage of each stone type and the association with sex and age in Chinese stone formers presenting with the first stone episode. The overall sex ratio (male:female) was 2.34:1. Results showed that the preponderant type of stone was calcium oxalate, followed by carbapatite, anhydrous uric acid, struvite and cystine. Struvite stones in this study accounted for a relatively low rate compared to that reported by others. Of 5,248 stones, only 38.1% had one component, 42.5% consisted of two components, and 20.4% consisted of three components. Our results also showed the higher percentage of carbapatite stones in females than in males and the increment of anhydrous uric acid stones with age. In addition, the percentage of calcium oxalate stones decreased with increase in the percentage of carbapatite stones over the period.


Asunto(s)
Cálculos Urinarios/química , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Apatitas/análisis , Pueblo Asiatico , Oxalato de Calcio/análisis , Niño , Preescolar , China , Cistina/análisis , Femenino , Humanos , Lactante , Compuestos de Magnesio/análisis , Masculino , Persona de Mediana Edad , Fosfatos/análisis , Factores Sexuales , Espectroscopía Infrarroja por Transformada de Fourier , Estruvita , Ácido Úrico/análisis , Adulto Joven
14.
iScience ; 24(4): 102363, 2021 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-33898950

RESUMEN

AMP-activated protein kinase (AMPK) senses energy status and impacts energy-consuming events by initiating metabolism regulatory signals in cells. Accumulating evidences suggest a role of AMPK in mitosis regulation, but the mechanism of mitotic AMPK activation and function remains elusive. Here we report that AMPKα2, but not AMPKα1, is sequentially phosphorylated and activated by CDK1 and PLK1, which enables AMPKα2 to accurately guide chromosome segregation in mitosis. Phosphorylation at Thr485 by activated CDK1-Cyclin B1 brings the ST-stretch of AMPKα2 to the Polo box domain of PLK1 for subsequent Thr172 phosphorylation by PLK1. Inserting of the AMPKα2 ST-stretch into AMPKα1, which lacks the ST-stretch, can correct mitotic chromosome segregation defects in AMPKα2-depleted cells. These findings uncovered a specific signaling cascade integrating sequential phosphorylation by CDK1 and PLK1 of AMPKα2 with mitosis to maintain genomic stability, thus defining an isoform-specific AMPKα2 function, which will facilitate future research on energy sensing in mitosis.

15.
Cell Rep ; 36(2): 109343, 2021 07 13.
Artículo en Inglés | MEDLINE | ID: mdl-34260926

RESUMEN

Stable transmission of genetic material during cell division requires accurate chromosome segregation. PLK1 dynamics at kinetochores control establishment of correct kinetochore-microtubule attachments and subsequent silencing of the spindle checkpoint. However, the regulatory mechanism responsible for PLK1 activity in prometaphase has not yet been affirmatively identified. Here we identify Apolo1, which tunes PLK1 activity for accurate kinetochore-microtubule attachments. Apolo1 localizes to kinetochores during early mitosis, and suppression of Apolo1 results in misaligned chromosomes. Using the fluorescence resonance energy transfer (FRET)-based PLK1 activity reporter, we found that Apolo1 sustains PLK1 kinase activity at kinetochores for accurate attachment during prometaphase. Apolo1 is a cognate substrate of PLK1, and the phosphorylation enables PP1γ to inactivate PLK1 by dephosphorylation. Mechanistically, Apolo1 constitutes a bridge between kinase and phosphatase, which governs PLK1 activity in prometaphase. These findings define a previously uncharacterized feedback loop by which Apolo1 provides fine-tuning for PLK1 to guide chromosome segregation in mitosis.


Asunto(s)
Proteínas de Ciclo Celular/metabolismo , Segregación Cromosómica , Retroalimentación Fisiológica , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Secuencias de Aminoácidos , Secuencia de Aminoácidos , Células HEK293 , Células HeLa , Humanos , Cinetocoros/metabolismo , Mitosis , Fosfoproteínas Fosfatasas/metabolismo , Fosforilación , Fosfoserina/metabolismo , Unión Proteica , Proteínas/química , Quinasa Tipo Polo 1
16.
J Urol ; 184(2): 665-8, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20639031

RESUMEN

PURPOSE: We evaluated the efficacy and safety of shock wave lithotripsy in the supine position through the greater and lesser ischiadic foramina as a path of shock wave to treat distal ureteral stones in young children. MATERIALS AND METHODS: We treated 22 young children with distal urinary calculi using the Dornier Compact S lithotriptor between 1997 and 2007. The study population consisted of 15 boys and 7 girls 6 months to 7 years old (mean +/- SD 5.4 +/- 2.1 years). Stone size ranged from 5 to 16 mm (mean 6.8). All patients were treated in the supine position under dissociative anesthesia with ketamine. The focused shock wave targeted the stone in the distal ureter through the greater and lesser ischiadic foramina. RESULTS: Number of shocks ranged from 600 to 3,000 (mean +/- SD 2,346.2 +/- 483.7). Energy per pulse ranged from level 4 to 5 (mean 4.5). Treatment time varied from 20 to 40 minutes (mean 31). Stone-free rate at 2 weeks after lithotripsy was 77.3%, which increased to 100% at 3 months after a single lithotripsy session. No serious side effects were observed. CONCLUSIONS: Shock wave lithotripsy in the supine position through the greater and lesser ischiadic foramina as the path of shock wave treats distal ureteral stones in young children with an excellent success rate and few side effects.


Asunto(s)
Litotricia/métodos , Cálculos Ureterales/terapia , Niño , Preescolar , Femenino , Humanos , Lactante , Isquion , Masculino , Posicionamiento del Paciente , Posición Supina , Cálculos Ureterales/patología
17.
Urol Res ; 38(6): 417-20, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20625895

RESUMEN

The purpose of the study is to evaluate the efficacy and safety of shock wave lithotripsy (SWL) using sciaticum majus foramen and sciaticum minus foramen as the path to treat distal ureteral stone in supine position. Between December 2006 and November 2008, 243 cases of distal urinary calculi were treated in our department using SWL or ureteroscopy. 189 cases for SWL were treated in supine position. The shockwave target on the stone in distal ureter via sciaticum majus foramen and sciaticum minus foramen, avoiding the sacroiliac joint. 54 cases were underwent ureteroscopy combined with holmium:YAG laser lithotripsy. The stone-free rate and the efficacy quotient (EQ) for SWL and ureteroscopy was 81.5%, 0.68; 94.4%, 0.78; respectively (p = 0.02). The retreatment rate for SWL and ureteroscopy was 14.6%, 0, respectively. The number of the shocks ranged from 600 to 3,000 (mean 2,566.3 ± 378.8). The energy per pulse of SWL ranged from 8 to 12 kV (mean 10.7). SWL in the supine position using sciaticum majus foramen and sciaticum minus foramen as the path is a choice of the treatment of distal ureteral stones with an excellent success rate and low side effect.


Asunto(s)
Litotricia/métodos , Posicionamiento del Paciente , Cálculos Ureterales/terapia , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Posición Supina , Ureteroscopía
18.
Zhonghua Yi Xue Za Zhi ; 90(34): 2433-5, 2010 Sep 14.
Artículo en Zh | MEDLINE | ID: mdl-21092517

RESUMEN

OBJECTIVE: To employ a newly modified rat model for infection-induced bladder stone formation. METHODS: 24 adult male Sprague Dawley rats were divided into 3 groups, model group (n=12), sham operation group (n=8) and control group (n=4). The surgical procedures were performed aseptically under anesthesia (25% Ultane 1.0 g/kg). The bladder in model group was exposed through a short lower midline abdominal incision, the puncture needle (G18) with guideline was inserted aseptically into bladder, a metal wire, which have been contaminated by the Proteus mirabilis, was put into the puncture canal, then implanted into the bladder lumen through the guideline. In the sham operated group the puncture needle (G18) with guideline was inserted into bladder without metal wire implanted into the bladder. There was no any operation in control group. The rats were sacrificed by excessive anesthesia at 21 days post challenge. The bladder were removed aseptically and inspected for evidence of urolithiasis. RESULTS: On Day 2 after surgery, two rats died in model group, no rats died in other groups. Twenty-one days after surgery, all of rats in model group developed various-sized bladder stones. There was no stone formation in sham operation group and control group. All stones were verified by infrared spectroscopy and optical crystallography. These stone were struvite stone. CONCLUSION: This model has a less trauma, faster recovery and excellent stone formation so that it may be used for the study of infection stone.


Asunto(s)
Modelos Animales de Enfermedad , Cálculos de la Vejiga Urinaria , Vejiga Urinaria , Animales , Infecciones , Masculino , Ratas , Ratas Sprague-Dawley , Vejiga Urinaria/microbiología , Cálculos de la Vejiga Urinaria/microbiología
19.
Exp Ther Med ; 20(3): 2209-2217, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32765697

RESUMEN

The aim of the present study was to develop a circulating microRNA expression signature for early prediction of osteoporotic fractures and to validate the results using Gene Expression Omnibus (GEO) datasets. The GSE70318 dataset was downloaded from GEO and used to build an osteoporotic fracture prediction model based on the receiver operating characteristic curve and support vector machine (SVM) classification index. The GSE74209 dataset was used as a validation dataset. Additionally, in vitro, alkaline phosphatase (ALP) activity was measured in the presence or absence of microRNA (miRNA/miR) treatments in human osteoblast cells. The expression of two selected genes was detected by western blotting. miR-188-3p, miR-942-3p, miR-576-3p and miR-135a-5p were differentially expressed between controls and osteoporotic patients with fractures. SVM classification using these four miRNAs provided better dichotomization. It was further confirmed that miR-576-3p and 135a-5p in the GSE74209 dataset could also significantly discriminate between the controls and fracture patients, the area under the curve of SVM2 was 0.9722 with 95% CI 0.8885-1.056. Further analysis indicated that the target genes of the two miRNAs participated in the Wingless-related integration site, Hedgehog and transforming growth factor-ß signaling pathways and osteoclast differentiation. miR-576-3p and miR-135-5p transfection decreased ALP activity and ALP activity was increased in the presence of blocking antisense oligonucleotides. Western blotting indicated miR-576-3p and miR-135-5p decreased CSNK1A1L and LRP6 levels, respectively. In conclusion, two miRNA signatures were developed and validated for the prediction of osteoporotic fractures.

20.
Pediatr Surg Int ; 25(12): 1109-12, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19816698

RESUMEN

PURPOSE: In this study, we retrospectively analyzed our experience with extracorporeal shock wave lithotripsy (ESWL) in children with ureteric stones. MATERIALS AND METHODS: Between 1997 and 2008, 115 children with ureteral stones were treated by ESWL in our department. There were 67 boys and 48 girls with a mean age of 7.2 + or - 4.3 years. There were 53 (46.1%) patients with proximal ureteric stones, 16 (13.9%) with mid-ureteral stones and 46 (40.0%) with distal ureteral stones. The stone size ranged from 4 to 21 mm with a mean of 7.38 mm. Children with proximal stones were treated in the supine position, while children with mid and distal ureteric stones were treated in the prone or supine position. RESULTS: Stone-free rate at 3 months was 94.8%, the re-treatment rate 15.7%, and overall efficacy quotient (EQ) was 83%. SWL failed in six children (5.2%). There was no significant difference in stone-free rates at 3 months between different groups classified by location and stone size. There were no serious side effects. CONCLUSIONS: Our results indicate that ESWL with highly satisfactory stone-free rates and negligible complications can be considered as a first-line treatment for ureteric stones in the pediatric age group.


Asunto(s)
Litotricia/métodos , Cálculos Ureterales/terapia , Adolescente , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Cálculos Ureterales/diagnóstico , Urografía
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