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1.
J Neurochem ; 2024 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-39183510

RESUMEN

Epidermal growth factor (EGF) is known to be a critical stimulant for inducing the proliferation of glioma cancer cells. In our study, we observed that GST-RhoA binds to pyruvate kinase M2 (PKM2) in vitro. While EGF reduced the levels of RhoA protein, it significantly increased p-Y42 RhoA, as well as PKM1 and PKM2 in LN18 glioma cell line. We determined that RhoA undergoes degradation through ubiquitination involving SCF1 and Smurf1. Interestingly, we observed that p-Y42 RhoA binds to PKM2, while the dephosphomimetic form, RhoA Y42F, did not. Additionally, our observation revealed that PKM2 stabilized both RhoA and p-Y42 RhoA. Importantly, RhoA, p-Y42 RhoA, and PKM2, but not RhoA-GTP, were localized in the nucleus upon EGF stimulation. Knockdown of RhoA with siRNA resulted in the reduced levels of phosphoglycerate kinase1 (PGK1) and microtubule affinity-regulating kinase 4 (MARK). Furthermore, we found that the promoter of PGK1 was associated with ß-catenin and YAP. Notably, p-Y42 RhoA and PKM2 co-immunoprecipitated with ß-catenin and YAP. Based on these findings, we proposed a novel mechanism by which p-Y42 RhoA and PKM2, in conjunction with ß-catenin and YAP, regulate PGK1 expression, contributing to the progression of glioma upon EGF.

2.
Bull Entomol Res ; 113(4): 565-573, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37434448

RESUMEN

Arthropod species diversity enhances ecosystem productivity and sustainability by increasing pollination and biological control services. Although, it is declining rapidly due to conventional agricultural intensification, organic agriculture with reduced reliance on agronomic inputs can regenerate ecosystems' resilience and restore them. Here, we report whether hexapod communities differ on both types of farming systems in small-scale field plot experiments, wherein Maize variety AG-589 was grown organically and conventionally in the 2020 and 2021 seasons. Livestock manure was applied in organic fields, whereas nitrogen and phosphorous were used as synthetic fertilizers in conventional fields. Hexapods were sampled three weeks after sowing once a week from the middle rows of subplots from both organically and conventionally grown maize. Twelve species of herbivores and four species of predators were recorded. Hexapod abundance overall and that of herbivores only was higher in conventionally cultivated maize, while predator abundance was higher in organic maize. Herbivores species diversity and evenness were significantly higher in conventional maize. Predator species diversity and evenness were significantly higher in organic maize fields. We noted predator abundance, diversity, and evenness as strong predictors to lower herbivore populations. These findings suggest that organic farming conserves natural enemies' biodiversity and regulates herbivores with increased provision of suitable habitats and prey resources for natural enemies, leading to enhanced relative abundance in their specialized niches. Thus, organic agriculture can potentially mediate better ecosystem services.


Asunto(s)
Artrópodos , Ecosistema , Animales , Agricultura Orgánica , Zea mays , Insectos , Biodiversidad , Agricultura
3.
J Cell Physiol ; 237(1): 128-148, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34311499

RESUMEN

Glucose metabolism is a mechanism by which energy is produced in form of adenosine triphosphate (ATP) by mitochondria and precursor metabolites are supplied to enable the ultimate enrichment of mature metabolites in the cell. Recently, glycolytic enzymes have been shown to have unconventional but important functions. Among these enzymes, pyruvate kinase M2 (PKM2) plays several roles including having conventional metabolic enzyme activity, and also being a transcriptional regulator and a protein kinase. Compared with the closely related PKM1, PKM2 is highly expressed in cancer cells and embryos, whereas PKM1 is dominant in mature, differentiated cells. Posttranslational modifications such as phosphorylation and acetylation of PKM2 change its cellular functions. In particular, PKM2 can translocate to the nucleus, where it regulates the transcription of many target genes. It is notable that PKM2 also acts as a protein kinase to phosphorylate several substrate proteins. Besides cancer cells and embryonic cells, astrocytes also highly express PKM2, which is crucial for lactate production via expression of lactate dehydrogenase A (LDHA), while mature neurons predominantly express PKM1. The lactate produced in cancer cells promotes tumor progress and that in astrocytes can be supplied to neurons and may act as a major source for neuronal ATP energy production. Thereby, we propose that PKM2 along with its different posttranslational modifications has specific purposes for a variety of cell types, performing unique functions.


Asunto(s)
Leucemia Mieloide Aguda , Piruvato Quinasa , Adenosina Trifosfato/metabolismo , Línea Celular Tumoral , Glucólisis/fisiología , Humanos , Lactatos , Proteínas Quinasas/metabolismo , Piruvato Quinasa/genética
4.
Int J Environ Health Res ; 32(11): 2359-2375, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34374325

RESUMEN

This study aims to explore the impact of climate change on health, including local adaptation strategies. A mixed-method approach has been used in this study. The results reveal that increasing the frequency of flooding, severity of riverbank erosion and drought, and rising disease outbreak are the highest indicators of climate change perceived by riverine island (char) dwellers, which is similar to the observed data. It also uncovers, approximately all respondents encounter several health-related issues during different seasons where prevailing cold and cough with fever, skin diseases, and diarrhoea are the leading ailments. Several adaptation strategies are accommodated by char inhabitants in order to enhance resilience against the climate change health impacts, but the paucity of money, disrupted communication, lack of formal health-care centre are the most obstacles to the sustainability of adaptation. This research recommends that healthcare-associated project should be performed through proper monitoring for exterminating char dwellers' health issues.


Asunto(s)
Cambio Climático , Bangladesh/epidemiología , Humanos
5.
Sensors (Basel) ; 21(21)2021 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-34770547

RESUMEN

This paper presents a systematic and efficient design approach for the two degree-of-freedom (2-DoF) capacitive microelectromechanical systems (MEMS) accelerometer by using combined design and analysis of computer experiments (DACE) and Gaussian process (GP) modelling. Multiple output responses of the MEMS accelerometer including natural frequency, proof mass displacement, pull-in voltage, capacitance change, and Brownian noise equivalent acceleration (BNEA) are optimized simultaneously with respect to the geometric design parameters, environmental conditions, and microfabrication process constraints. The sampling design space is created using DACE based Latin hypercube sampling (LHS) technique and corresponding output responses are obtained using multiphysics coupled field electro-thermal-structural interaction based finite element method (FEM) simulations. The metamodels for the individual output responses are obtained using statistical GP analysis. The developed metamodels not only allowed to analyze the effect of individual design parameters on an output response, but to also study the interaction of the design parameters. An objective function, considering the performance requirements of the MEMS accelerometer, is defined and simultaneous multi-objective optimization of the output responses, with respect to the design parameters, is carried out by using a combined gradient descent algorithm and desirability function approach. The accuracy of the optimization prediction is validated using FEM simulations. The behavioral model of the final optimized MEMS accelerometer design is integrated with the readout electronics in the simulation environment and voltage sensitivity is obtained. The results show that the combined DACE and GP based design methodology can be an efficient technique for the design space exploration and optimization of multiphysics MEMS devices at the design phase of their development cycle.


Asunto(s)
Sistemas Microelectromecánicos , Aceleración , Simulación por Computador , Computadores , Distribución Normal
6.
Ann Hum Genet ; 84(1): 54-71, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31583691

RESUMEN

Mutations in the SMPX gene can disrupt the regular activity of the SMPX protein, which is involved in the hearing process. Recent reports showing a link between nonsynonymous single-nucleotide polymorphisms (nsSNPs) in SMPX and hearing loss, thus classifying deleterious SNPs in SMPX will be an uphill task before designing a more extensive population study. In this study, damaging nsSNPs of SMPX from the dbSNP database were identified by using 13 bioinformatics tools. Initially, the impact of nsSNPs in the SMPX gene were evaluated through different in silico predictors; and the deleterious convergent changes were analyzed by energy-minimization-guided residual network analysis. In addition, the pathogenic effects of mutations in SMPX-mediated protein-protein interactions were also characterized by structural modeling and binding energy calculations. A total of four mutations (N19D, A29T, K54N, and S71L) were found to be highly deleterious by all the tools, which are located at highly conserved regions. Furthermore, all four mutants showed structural alterations, and the communities of amino acids for mutant proteins were readily changed, compared to the wild-type. Among them, A29T (rs772775896) was revealed as the most damaging nsSNP, which caused significant structural deviation of the SMPX protein, as a result reducing the binding affinity to other functional partners. These findings reflect the computational insights into the deleterious role of nsSNPs in SMPX, which might be helpful for subjecting wet-lab confirmatory analysis.


Asunto(s)
Simulación por Computador , Bases de Datos Genéticas , Pérdida Auditiva/genética , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Polimorfismo de Nucleótido Simple , Pérdida Auditiva/patología , Humanos , Modelos Moleculares , Proteínas Musculares/química , Conformación Proteica , Mapas de Interacción de Proteínas , Estabilidad Proteica
7.
Biochem Biophys Res Commun ; 523(4): 972-978, 2020 03 19.
Artículo en Inglés | MEDLINE | ID: mdl-31973815

RESUMEN

Optimal levels of reactive oxygen species (ROS) play a critical role in cellular physiological function. For production of intracellular superoxide, NADPH oxidase is one of the sources. Rac1/2 and RhoA GTPases are involved in regulation of NADPH oxidase activity and Tyr42 phosphorylation of RhoA (p-Tyr42 RhoA) seems significant in this regard as it was recently shown that hydrogen peroxide was able to increase p-Tyr42 RhoA levels. Phorbol myristate acetate (PMA), a tumor promoter, also induces production of superoxides; PMA activates Src, a tyrosine kinase, and increases p-Tyr42 RhoA levels. In exploring the mechanism of PMA effects, we reduced RhoA levels in test cells with si-RhoA and then restoration of various versions of RhoA for effect in response of the cells to PMA and producing superoxides. Restoration of RhoA Y42F (a dephospho-mimic form) still had reduced superoxide formation in response to PMA, compared with WT and Y42E RhoA. This was similarly seen with assays for cell migration and proliferation with cells responding to PMA. Y27632, a ROCK (Rho associated coiled coil kinase) inhibitor, also inhibited superoxide production, and also reduced p-Y416 Src and p-p47phox levels. A ROCK active fragment was also able to phosphorylate p47phox at Ser345 residue (p-Ser345 p47phox), a component of NADPH oxidase. Overall, we demonstrate that p-Tyr42 RhoA levels increase following PMA treatment and this is through production of superoxide and activation of Src. These in turn amplify superoxide production through ROCK phophorylation of p47phox and maintain a positive feedback loop for superoxide generation, and contribute to tumor progression.


Asunto(s)
NADPH Oxidasas/metabolismo , Fosfotirosina/metabolismo , Superóxidos/metabolismo , Quinasas Asociadas a rho/metabolismo , Proteína de Unión al GTP rhoA/metabolismo , Células A549 , Animales , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Humanos , Ratones , Fosforilación , Células RAW 264.7 , Acetato de Tetradecanoilforbol/farmacología , Familia-src Quinasas/metabolismo
8.
Urol Int ; 95(3): 293-9, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25765088

RESUMEN

OBJECTIVE: The objective was to assess and publish our first experiences with the GreenLight XPS™ 180-watt laser in men suffering from bladder outlet obstruction. PATIENTS AND METHODS: From January 2013 to February 2014, the results of 142 patients were analyzed prospectively at a single center. Indications for disobstruction were in line with current EAU guidelines, but independent of the underlying causes of obstruction. Assessments were made of the prostate size, International Prostate Symptom Score (IPSS), postvoid residual (PVR) and maximum urinary flow (Qmax). Intraoperative data such as lasing time, surgery time, applied energy and blood transfusions were recorded. Reinterventions and complications were evaluated. RESULTS: The average prostate volume was 29.6 ml (2-82). The average surgery time was 50 min (13-157). Qmax increased by an average of 20.2 ml/s (p < 0.05). On average, PVR was reduced by 162 ml (p < 0.05). CONCLUSION: The GreenLight XPS™ 180-watt laser is an effective treatment option for bladder outlet obstruction with a low perioperative complications rate, and it shows results comparable with transurethral resection of the prostate. Even multimorbid patients and patients with long-term catheter requirements may be treated due to its high safety profile and reliable results.


Asunto(s)
Terapia por Láser/instrumentación , Prostatectomía/métodos , Obstrucción del Cuello de la Vejiga Urinaria/cirugía , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos
9.
Urologie ; 63(1): 67-74, 2024 Jan.
Artículo en Alemán | MEDLINE | ID: mdl-37747493

RESUMEN

BACKGROUND: In addition to erectile dysfunction, urinary incontinence is the most common functional limitation after radical prostatectomy (RPE) for prostate cancer (PCa). The German S3 guideline recommends informing patients about possible effects of the therapy options, including incontinence. However, only little data on continence from routine care in German-speaking countries after RPE are currently available, which makes it difficult to inform patients. OBJECTIVE: The aim of this work is to present data on the frequency and severity of urinary incontinence after RPE from routine care. MATERIALS AND METHODS: Information from the PCO (Prostate Cancer Outcomes) study is used, which was collected between 2016 and 2022 in 125 German Cancer Society (DKG)-certified prostate cancer centers in 17,149 patients using the Expanded Prostate Cancer Index Composite Short Form (EPIC-26). Changes in the "incontinence" score before (T0) and 12 months after RPE (T1) and the proportion of patients who used pads, stratified by age and risk group, are reported. RESULTS: The average score for urinary incontinence (value range: 0-worst possible to 100-best possible) was 93 points at T0 and 73 points 12 months later. At T0, 97% of the patients did not use a pad, compared to 56% at T1. 43% of the patients who did not use a pad before surgery used at least one pad a day 12 months later, while 13% use two or more. The proportion of patients using pads differs by age and risk classification. CONCLUSION: The results provide a comprehensive insight into functional outcome 12 months after RPE and can be taken into account when informing patients.


Asunto(s)
Disfunción Eréctil , Neoplasias de la Próstata , Incontinencia Urinaria , Masculino , Humanos , Incontinencia Urinaria/epidemiología , Disfunción Eréctil/epidemiología , Neoplasias de la Próstata/cirugía , Prostatectomía/efectos adversos
10.
BJU Int ; 111(2): 296-303, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23186285

RESUMEN

OBJECTIVE: To report our experience with a new self-anchoring adjustable transobturator male system (ATOMS®; AMI, Vienna, Austria) for the treatment of stress urinary incontinence (SUI) in men. PATIENTS AND METHODS: A total of 99 men, in a number of centres, were treated for SUI with the new ATOMS® device. The device was implanted in all patients using an outside-in technique by passing the obturator foramen and anchoring the device to the inferior pubic ramus. The titanium port was placed s.c. on the left symphysis region. Adjustments were performed via port access. Postoperative evaluation consisted of physical examination, 24-h pad test, and 24 h-pad count. Preoperatively and at 6-month follow-up, patients completed a validated quality-of-life questionnaire. Two-way ANOVA was used to analyse changes over time. Within-group effects for time were tested using post hoc Dunnett's contrasts of baseline values vs subsequent measurements. RESULTS: The most common indication was SUI after radical prostatectomy (92.9%). Failure of previous surgeries was present in 34.3% patients and 31.3% patients had undergone secondary radiation. The mean (SD; range) surgery time was 47 (13.8; 29-112) min. Temporary urinary retention occurred in two patients (2%) and transient perineal/scrotal dysaesthesia or pain was reported by 68 patients (68.7%) and resolved after 3-4 weeks of non-opioid analgesics. There were four (4%) cases of wound infection at the site of the titanium port leading to explantation. No urethral or bladder injuries related to the device or erosions occurred. The mean (SD; range) number of adjustments to reach the desired result (dryness, improvement and/or patient satisfaction) was 3.8 (1.3; 1-6). After a mean (SD; range) follow-up time of 17.8 (1.6; 12-33) months, the overall success rate was 92% and the mean pad use decreased from 7.1 to 1.3 pads/24 h (P < 0.001). Overall, 63% were considered dry and 29% were improved. CONCLUSION: Treatment of male SUI with this self-anchored adjustable system is safe and effective.


Asunto(s)
Cabestrillo Suburetral , Incontinencia Urinaria de Esfuerzo/cirugía , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Humanos , Masculino , Persona de Mediana Edad , Tempo Operativo , Cuidados Posoperatorios , Complicaciones Posoperatorias/etiología , Estudios Prospectivos , Prostatectomía/efectos adversos , Diseño de Prótesis , Calidad de Vida , Incontinencia Urinaria de Esfuerzo/etiología , Esfínter Urinario Artificial
11.
Aktuelle Urol ; 54(5): 365-368, 2023 09.
Artículo en Alemán | MEDLINE | ID: mdl-37339666

RESUMEN

Primary malignant melanoma of the urinary tract is a rare entity with less than 50 cases reported worldwide. The following case concerns a 64-year-old woman whom we first saw in our emergency room due to gross haematuria. As part of the subsequent diagnostic investigation, we detected a primary malignant melanoma of the bladder and the urethra. The patient was treated with radical urethrocystectomy including pelvic lymphadenectomy and an ileum conduit. This was followed by a year of adjuvant therapy using checkpoint inhibitors.


Asunto(s)
Melanoma , Neoplasias Cutáneas , Femenino , Humanos , Persona de Mediana Edad , Vejiga Urinaria/cirugía , Vejiga Urinaria/patología , Melanoma/diagnóstico , Melanoma/cirugía , Neoplasias Cutáneas/patología , Uretra , Melanoma Cutáneo Maligno
12.
Micromachines (Basel) ; 14(4)2023 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-37421050

RESUMEN

This paper presents a deep neural network (DNN) based design optimization methodology for dual-axis microelectromechanical systems (MEMS) capacitive accelerometer. The proposed methodology considers the geometric design parameters and operating conditions of the MEMS accelerometer as input parameters and allows to analyze the effect of the individual design parameters on the output responses of the sensor using a single model. Moreover, a DNN-based model allows to simultaneously optimize the multiple output responses of the MEMS accelerometers in an efficient manner. The efficiency of the proposed DNN-based optimization model is compared with the design of the computer experiments (DACE) based multiresponse optimization methodology presented in the Literature, which showed a better performance in terms of two output performance metrics, i.e., mean absolute error (MAE) and root mean squared error (RMSE).

13.
Antioxidants (Basel) ; 12(12)2023 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-38136210

RESUMEN

Inflammation plays a crucial role in tumorigenesis, primarily mediated by NF-κB. RhoA GTPases are instrumental in regulating the activation of NF-κB. Specifically, the phosphorylation of Tyrosine 42 on RhoA ensures the activation of NF-κB by directly activating the IKKß associated with IKKγ (NEMO). This study aimed to uncover the molecular mechanism through which p-Tyrosine 42 RhoA, in conjunction with NF-κB, promotes tumorigenesis. Notably, we observed that p-Tyrosine 42 RhoA co-immunoprecipitated with the p-Ser 536 p65/RelA subunit in NF-κB in response to LPS. Moreover, both p-Tyrosine 42 RhoA and p-p65/RelA translocated to the nucleus, where they formed a protein complex associated with the promoter of phosphoglycerate kinase 1 (PGK1) and regulated the expression of PGK1. In addition, p-p65/RelA and p-Tyr42 RhoA co-immunoprecipitated with p300 histone acetyltransferase. Intriguingly, PGK1 exhibited an interaction with ß-catenin, PKM1 and PKM2. Of particular interest, si-PGK1 led to a reduction in the levels of ß-catenin and phosphorylated pyruvate dehydrogenase A1 (p-PDHA1). We also found that PGK1 phosphorylated ß-catenin at the Thr551 and Ser552 residues. These findings discovered that PGK1 may play a role in transcriptional regulation, alongside other transcription factors.

14.
Free Radic Biol Med ; 208: 614-629, 2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37722568

RESUMEN

In the tumor microenvironment (TME), communication between cancer cells and tumor-associated macrophages (TAMs) through secreted extracellular proteins promotes cancer progression. Here, we observed that co-culturing cancer cells (4T1) and macrophage cells (Raw264.7) significantly enhanced superoxide production in both cell types. Using MALDI-TOF, we identified PKM2 as a highly secreted protein by Raw264.7 cells and bone marrow-derived monocytes. The extracellular recombinant PKM2 protein not only enhanced cancer cell migration and invasion but also increased superoxide production. Additionally, PKM2 was found to associate with the cell surface, and its binding to integrin α5/ß1 receptor was inhibited by antibodies specifically targeting it. Furthermore, we investigated downstream signaling pathways involved in PKM2-induced superoxide production. We found that knock-down of RhoA and p47phox using siRNAs effectively abolished superoxide generation in response to extracellular PKM2. Notably, extracellular PKM2 triggered the phosphorylation of p47phox at Ser345 residue and RhoA at Tyr42 residue (p-Tyr42 RhoA). Moreover, extracellular PKM2 exerted regulatory control over the expression of key epithelial-mesenchymal transition (EMT) markers, including ZEB1, Snail1, vimentin, and E-cadherin. Interestingly, p-Tyr42 RhoA translocated to the nucleus, where it bound to the ZEB1 promoter region. In light of these findings, we propose that extracellular PKM2 within the TME plays a critical role in tumorigenesis by promoting cancer cell migration and invasion through RhoA/p47phox signaling pathway.


Asunto(s)
Neoplasias , Superóxidos , Humanos , Línea Celular Tumoral , Movimiento Celular , Transición Epitelial-Mesenquimal/genética , Piruvato Quinasa/genética , Piruvato Quinasa/metabolismo , Transducción de Señal , Microambiente Tumoral/genética , Animales , Ratones , Proteínas de Unión a Hormona Tiroide
15.
Chemosphere ; 330: 138572, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37088212

RESUMEN

Microplastics (MPs) are widely distributed in the marine environment, posing a significant threat to marine biota. The contribution of anthropogenic and terrestrial sources to the aquatic ecosystem has led to an increase in MPs findings, and their abundance in aquatic biota has been reported to be of concern. MPs are formed mainly via photo degradation of macroplastics (large plastic debris), and their release into the environment is a result of the degradation of additives. Eco-toxicological risks are increasing for marine organisms, due to the ingestion of MPs, which cause damage to gastrointestinal (GI) tracts and stomach. Plastics with a size <5 mm are considered MPs, and they are commonly identified by Raman spectroscopy, Fourier transfer infrared (FTIR) spectroscopy, and Laser direct infrared (LDIR). The size, density and additives are the main factors influencing the abundance and bioavailability of MPs. The most abundant type of MPs found in fishes are fiber, polystyrenes, and fragments. These microscale pellets cause physiological stress and growth deformities by targeting the GI tracts of fishes and other biota. Approximately 80% MPs come from terrestrial sources, either primary, generated during different products such as skin care products, tires production and the use of MPs as carrier for pharmaceutical products, or secondary plastics, disposed of near coastal areas and water bodies. The issue of MPs and their potential effects on the marine ecosystem require proper attention. Therefore, this study conducted an extensive literature review on assessing MPs levels in fishes, sediments, seawater, their sources, and effects on marine biota (especially on fishes), chemo-physical behavior and the techniques used for their identification.


Asunto(s)
Plásticos , Contaminantes Químicos del Agua , Animales , Plásticos/química , Microplásticos , Ecosistema , Contaminantes Químicos del Agua/análisis , Organismos Acuáticos , Peces , Monitoreo del Ambiente/métodos
16.
Biomolecules ; 14(1)2023 12 20.
Artículo en Inglés | MEDLINE | ID: mdl-38275747

RESUMEN

Cell migration is a crucial contributor to metastasis, a critical process associated with the mortality of cancer patients. The initiation of metastasis is triggered by epithelial-mesenchymal transition (EMT), along with the changes in the expression of EMT marker proteins. Inflammation plays a significant role in carcinogenesis and metastasis. Lipopolysaccharide (LPS), a typical inflammatory agent, promoted the generation of superoxide through the activation of p-Tyr42 RhoA, Rho-dependent kinase 2 (ROCK2), and the phosphorylation of p47phox. In addition, p-Tyr42 RhoA activated phospholipase D1 (PLD1), with PLD1 and phosphatidic acid (PA) being involved in superoxide production. PA also regulated the expression of EMT proteins. Consequently, we have identified MHY9 (Myosin IIA, NMIIA) as a PA-binding protein in response to LPS. MYH9 also contributed to cell migration and the alteration in the expression of EMT marker proteins. Co-immunoprecipitation revealed the formation of a complex involving p-Tyr42 RhoA, PLD1, and MYH9. These proteins were found to be distributed in both the cytosol and nucleus. In addition, we have found that p-Tyr42 RhoA PLD1 and MYH9 associate with the ZEB1 promoter. The suppression of ZEB1 mRNA levels was achieved through the knockdown of RhoA, PLD1, and MYH9 using si-RNAs. Taken together, we propose that p-Tyr42 RhoA and PLD1, responsible for producing PA, and PA-bound MYH9 are involved in the regulation of ZEB1 expression, thereby promoting cell migration.


Asunto(s)
Lipopolisacáridos , Fosfolipasa D , Transducción de Señal , Humanos , Movimiento Celular , Lipopolisacáridos/farmacología , Ácidos Fosfatidicos/metabolismo , Transducción de Señal/fisiología , Superóxidos
17.
Clin Transplant ; 26(6): 919-26, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22994923

RESUMEN

BACKGROUND: This prospective observational study documented long-term renal function in transplant recipients receiving mycophenolate mofetil (MMF). METHODS: Kidney allograft recipients>6 months post-transplantation, with a glomerular filtration rate (GFR)>20 mL/min, receiving MMF from time of transplantation were enrolled and followed for four yr. Subgroups were identified based on time between transplantation and enrollment: Y<1 (6 months-1 yr); Y1-2 (>1-2 yr); Y2-5 (>2-5 yr) and Y>5 (>5 yr). RESULTS: A total of 2040 patients were analyzed; 780, 410, 541 and 309 in subgroups Y<1, Y1-2, Y2-5 and Y>5. For all patients combined GFR decreased during the observational period by approximately 1 mL/min/yr (median GFR (mL/min) was 50.8, 50.5, 48.7, and 47.6 at one, two, three, and four yr). Survival estimates for decline in renal function (>20% GFR decline at one time point) were 78%, 66%, 57%, and 51% at one, two, three and four yr, with no significant differences between subgroups (p>0.05). In adult patients, higher doses of MMF (≥1 g/d) were associated with better GFR outcomes (median GFR (mL/min) 48.1 vs. 39.9 at four yr post-enrollment; p=0.0037). When comparing the effects of MMF combined with calcineurin inhibitors (CNIs), GFR was increased with lower doses of tacrolimus or cyclosporin. There were no major tolerability or acute rejection problems and graft survival was similar in all subgroups (graft survival estimates for all patients combined were 99%, 95%, 92%, and 90% at one, two, three, and four yr). CONCLUSIONS: Long-term MMF immunosuppression preserves renal function and higher MMF doses combined with lower CNI doses may provide better patient outcomes.


Asunto(s)
Rechazo de Injerto/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Enfermedades Renales/cirugía , Trasplante de Riñón/efectos adversos , Ácido Micofenólico/análogos & derivados , Adulto , Manejo de la Enfermedad , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Rechazo de Injerto/etiología , Rechazo de Injerto/mortalidad , Supervivencia de Injerto , Humanos , Enfermedades Renales/complicaciones , Masculino , Persona de Mediana Edad , Ácido Micofenólico/uso terapéutico , Pronóstico , Estudios Prospectivos , Tasa de Supervivencia
18.
Aktuelle Urol ; 53(6): 552-558, 2022 12.
Artículo en Alemán | MEDLINE | ID: mdl-31559609

RESUMEN

BACKGROUND: Photodynamic Diagnosis (PDD) is widely used today for the diagnosis and treatment of superficial bladder cancer. This study aimed to analyse the impact of using this technique on recurrence rate, residual tumour rate and progression-free survival. MATERIALS AND METHODS: We conducted this study retrospectively in our unit between 10/2014 and 02/2018. We divided our patients into 2 groups: white light group, 49 patients who underwent primary bladder tumour resection with white light transurethral resection of bladder tumour (WL-TURB), and blue light group, 49 patients treated with blue light transurethral resection of bladder tumour (BL-TURB) with PDD. Patients in both groups were followed up for one year. We collected data for tumour recurrence for the first year, 3-month and 1-year relapse-free survival and 1-year progression-free assessment pursuant to the EORTC risk classification by Sylvester 2006. Furthermore, the residual tumour rate was determined by re-TURB. RESULTS: The following results were found independent of age, gender and histological findings: Residual tumour rate: blue light group 13.95 % vs. white light group 32.6 %, (p 0.02, OR 3.8, CI 95 % [1.17 - 12.85]).; 3-month relapse-free survival: blue light group 87.7 % vs. white light group 67.4 % (p 0.02, HR 3.18, CI 95 % [1.20 - 8.42]); 1-year relapse-free survival: blue light group 77.6 % vs. white light group 55.1 % (p 0.015, HR 2.56, CI 95 % [1.20 - 5.45]); 1-year progression-free survival: blue light group 95.9 % vs. white light group 79.6 %, p 0.03, HR 5.23, CI 95 % [1.11 - 24.53]) CONCLUSION: The use of hexaminolevulinate significantly reduces the risk of residual tumours compared with conventional TURB. The PDD technique significantly improved 3- and 12-month recurrence-free survival, especially in low and medium-risk tumours, and 1-year progression-free survival, especially in high-risk tumours.


Asunto(s)
Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/cirugía , Neoplasias de la Vejiga Urinaria/patología , Neoplasia Residual/diagnóstico , Neoplasia Residual/cirugía , Estudios Retrospectivos , Recurrencia Local de Neoplasia/cirugía , Pronóstico
19.
Aktuelle Urol ; 53(6): 564-566, 2022 12.
Artículo en Alemán | MEDLINE | ID: mdl-32126575

RESUMEN

The following is a case report of a 54-year-old female who presented with persistent macrohaematuria with bladder tamponade three weeks after percutaneous nephrolithotomy. Angiography revealed an intrarenal aneurysm, which was closed by coiling, resulting in complete cessation of bleeding.


Asunto(s)
Aneurisma , Cálculos Renales , Nefrolitotomía Percutánea , Femenino , Humanos , Persona de Mediana Edad , Aneurisma/diagnóstico por imagen , Aneurisma/cirugía , Cálculos Renales/cirugía
20.
Environ Pollut ; 311: 119961, 2022 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-35977638

RESUMEN

In the past few decades, contamination of urban children's parks (UCPs) with potentially toxic elements (PTEs) has been attracting more and more interest; however, assessment of eco-environmental and child exposure risks particularly in developing countries remains limited. The current study investigated PTE (Cr, Ni, Zn, As, Cd, and Pb) concentrations, potential sources, and their health risk assessment in UCP soils of 12 major cities in Pakistan. The results showed that the mean concentration of Ni exceeded the SEPA-permissible limit in all UCP sites, while other PTEs were found to be within acceptable limits. The soil properties such as pH, electrical conductivity, organic matter, and soil particles size were determined in UCPs soils. The contamination factor and pollution load index results indicated low to moderate pollution levels (CF < 3) and (PLI<1) for all PTEs except Ni in some of the selected cities. Quantile-quantile (Q-Q) plotting determined the normal distribution line for all PTEs in the UCPs. Principal component analysis showed the mixed sources of contamination from industrial emissions, fossil fuel combustion, vehicular emissions, wastewater irrigation, as well as solid waste disposal and natural sources of soil parent materials in all park sites. ANOVA results showed that all the PTEs except Cd had moderate to higher contamination values than the reference site. The risk assessment study revealed that children had high exposure to the selected PTEs via all exposure pathways. The hazard index (HI) mean value (1.82E+00) of Ni for all exposure pathways was greater than 1, while total risk value of Cr (1.00E-03) had exceeded USEPA limit, indicating cancer risk. Consequently, the study of UCPs soils revealed PTEs contamination that could pose a potential health risk to the local population in the studied UCPs regions of Pakistan. Thus, the present study recommends that the influx of PTEs originating from natural and anthropogenic sources should be mitigated and government should implement strict enforcement of environmental regulations and proper management, as well as air quality monitoring guidelines for public health should be strictly adopted to reduce traffic- and industrial emission-related to PTEs in metropolitan areas.


Asunto(s)
Metales Pesados , Contaminantes del Suelo , Cadmio/análisis , Niño , China , Monitoreo del Ambiente/métodos , Humanos , Metales Pesados/análisis , Pakistán , Medición de Riesgo , Suelo/química , Contaminantes del Suelo/análisis , Población Urbana , Aguas Residuales/análisis
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