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1.
Microbiol Spectr ; 12(6): e0051724, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38687019

RESUMEN

There is a growing interest in the use of probiotic bacteria as biosensors for the detection of disease. However, there is a lack of bacterial receptors developed for specific disease biomarkers. Here, we have investigated the use of the peptide-regulated transcription factor ComR from Streptococcus spp. for specific peptide biomarker detection. ComR exhibits a number of attractive features that are potentially exploitable to create a biomolecular switch for engineered biosensor circuitry within the probiotic organism Lactiplantibacillus plantarum WCFS1. Through iterative design-build-test cycles, we developed a genomically integrated, ComR-based biosensor circuit that allowed WCFS1 to detect low nanomolar concentrations of ComR's cognate peptide XIP. By screening a library of ComR proteins with mutant residues substituted at the K100 position, we identified mutations that increased the specificity of ComR toward an amidated version of its cognate peptide, demonstrating the potential for ComR to detect this important class of biomarker.IMPORTANCEUsing bacteria to detect disease is an exciting possibility under active study. Detecting extracellular peptides with specific amino acid sequences would be particularly useful as these are important markers of health and disease (biomarkers). In this work, we show that a probiotic bacteria (Lactiplantibacillus plantarum) can be genetically engineered to detect specific extracellular peptides using the protein ComR from Streptococcus bacteria. In its natural form, ComR allowed the probiotic bacteria to detect a specific peptide, XIP. We then modified XIP to be more like the peptide biomarkers found in humans and engineered ComR so that it activated with this modified XIP and not the original XIP. This newly engineered ComR also worked in the probiotic bacteria, as expected. This suggests that with additional engineering, ComR might be able to activate with human peptide biomarkers and be used by genetically engineered probiotic bacteria to better detect disease.


Asunto(s)
Proteínas Bacterianas , Péptidos , Factores de Transcripción , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Péptidos/metabolismo , Péptidos/genética , Probióticos/metabolismo , Mutación , Técnicas Biosensibles , Lactobacillus plantarum/genética , Lactobacillus plantarum/metabolismo , Regulación Bacteriana de la Expresión Génica , Streptococcus/genética , Streptococcus/metabolismo
2.
Eur Rev Med Pharmacol Sci ; 27(1): 103-109, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36647856

RESUMEN

OBJECTIVE: Pollen-food allergy syndrome (PFAS) is an IgE-mediated allergic reaction to certain foods due to prior sensitization to pollen allergens. The data about the prevalence of PFAS in adults in Turkey is not sufficiently reported. Our objective was to investigate the frequency and clinical features of PFAS in adult patients with seasonal allergic rhinitis (SAR). PATIENTS AND METHODS: A total of 222 patients with SAR were enrolled in our outpatient allergy clinic at Hacettepe University, during a ten-month period. A questionnaire was used to evaluate patients and to categorize those who experienced obvious allergy symptoms consistent with PFAS. Atopy was assessed by a standard skin prick test panel including common aeroallergen extracts. RESULTS: Among 222 patients with a diagnosis of SAR, 31 had patient reported PFAS (31/222, 14%). Among them, 23 (74.2%) were females, and their mean age was 32.29±9.24 years. The most common symptoms were isolated oropharyngeal symptoms (58.1%), followed by urticaria (51.6%) after culprit food ingestion. The most frequent culprit foods were eggplant, walnut, kiwi, peach, and melon. The predominant sensitizing aeroallergen was grass pollen. CONCLUSIONS: PFAS can be frequently observed in adults who are followed up for SAR. The most frequently involved foods are eggplant, walnut, kiwi, peach, and melon in Ankara Province. The symptoms of PFAS are usually localized in the oropharyngeal area and are self-limited.


Asunto(s)
Fluorocarburos , Hipersensibilidad a los Alimentos , Rinitis Alérgica Estacional , Femenino , Humanos , Adulto , Adulto Joven , Masculino , Rinitis Alérgica Estacional/diagnóstico , Rinitis Alérgica Estacional/epidemiología , Prevalencia , Hipersensibilidad a los Alimentos/diagnóstico , Hipersensibilidad a los Alimentos/epidemiología , Polen/efectos adversos , Alérgenos , Síndrome , Pruebas Cutáneas
3.
Niger J Clin Pract ; 25(12): 2016-2023, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36537460

RESUMEN

Aim: The primary aim of this study was to determine the risk factors for the occurrence of brachial plexus injury in cases of shoulder dystocia. Secondly, it was aimed to determine the factors affecting the occurrence of permanent sequelae in cases with brachial plexus injury. Subjects and Methods: ICD-10 codes were scanned from the records of patients who gave birth between 2012 and 2018, and the records of patients with brachial plexus injury and shoulder dystocia were reached. Shoulder dystocia cases with brachial plexus damage were accepted as the study group, and shoulder dystocia cases without brachial plexus damage were considered the control group. Shoulder dystocia patients with brachial plexus injury and without injury were compared for 2-year orthopedics clinic follow-up reports, surgical intervention, permanent sequelae status as well as birth data, maternal characteristics, and maneuvers applied to the management of shoulder dystocia. Results: Five hundred sixty births with shoulder dystocia were detected. Brachial plexus injury was observed in 88 of them, and permanent sequelae were detected in 12 of these patients. Maneuvers other than McRobert's (advanced maneuvers) were used more and clavicle fracture was seen more in the group with plexus injury (P < 0.05, P < 0.05, respectively). Logistic regression analysis was performed to determine the risk factors of brachial plexus injury. Brachial plexus injury was observed 4.746 times more in infants who were delivered with advanced maneuvers and 3.58 times more in infants with clavicle fractures at birth. Conclusion: In patients with shoulder dystocia, the risk of brachial plexus injury increased in deliveries in which advanced maneuvers were used and clavicle fracture occurred.


Asunto(s)
Plexo Braquial , Distocia , Fracturas Óseas , Distocia de Hombros , Embarazo , Recién Nacido , Femenino , Humanos , Parto Obstétrico , Distocia/epidemiología , Distocia/etiología , Plexo Braquial/lesiones , Fracturas Óseas/epidemiología , Progresión de la Enfermedad , Factores de Riesgo
4.
Mol Cancer Ther ; 21(12): 1846-1856, 2022 12 02.
Artículo en Inglés | MEDLINE | ID: mdl-36190964

RESUMEN

Tumor protein p63 (TP63) is a member of the TP53 protein family that are important for development and in tumor suppression. Unlike TP53, TP63 is rarely mutated in cancer, but instead different TP63 isoforms regulate its activity. TA isoforms (TAp63) act as tumor suppressors, whereas ΔN isoforms are strong drivers of squamous or squamous-like cancers. Many of these tumors become addicted to ΔN isoforms and removal of ΔN isoforms result in cancer cell death. Furthermore, some TP53 conformational mutants (TP53CM) gain the ability to interact with TAp63 isoforms and inhibit their antitumorigenic function, while indirectly promoting tumorigenic function of ΔN isoforms, but the exact mechanism of TP63-TP53CM interaction is unclear. The changes in the balance of TP63 isoform activity are crucial to understanding the transition between normal and tumor cells. Here, we modeled TP63-TP53CM complex using computational approaches. We then used our models to design peptides to disrupt the TP63-TP53CM interaction and restore antitumorigenic TAp63 function. In addition, we studied ΔN isoform oligomerization and designed peptides to inhibit its oligomerization and reduce their tumorigenic activity. We show that some of our peptides promoted cell death in a TP63 highly expressed cancer cell line, but not in a TP63 lowly expressed cancer cell line. Furthermore, we performed kinetic-binding assays to validate binding of our peptides to their targets. Our computational and experimental analyses present a detailed model for the TP63-TP53CM interaction and provide a framework for potential therapeutic peptides for the elimination of TP53CM cancer cells.


Asunto(s)
Carcinoma de Células Escamosas , Proteína p53 Supresora de Tumor , Humanos , Proteína p53 Supresora de Tumor/genética , Isoformas de Proteínas/metabolismo , Línea Celular Tumoral , Carcinogénesis , Carcinoma de Células Escamosas/metabolismo , Simulación por Computador , Factores de Transcripción/metabolismo , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo
5.
Actas Urol Esp (Engl Ed) ; 46(9): 544-549, 2022 11.
Artículo en Inglés, Español | MEDLINE | ID: mdl-36216767

RESUMEN

INTRODUCTION: The perioperative and postoperative concern in percutaneous nephrolithotomy (PNL) is bleeding. Disease-related conditions (such as stone size, stone HU, tract number, and diameter) affecting this situation were determined. To determine independent risk factors that may affect the amount of hemorrhage in PNL. MATERIAL AND METHOD: A total of 308 adult patients (211 men, 97 women) undergoing the PNL procedure were included in the study. Renal anatomy and stone size were evaluated using non-contrast thin-section computed tomography (NCCT). NCCT was used to assess Hounsfield unit (HU) values of kidney stones, presence of atheroma plaque and obesity. The difference between preoperative hemoglobin (Hgb) values and postoperative 1st day Hgb values was recorded. This variation was evaluated for the effect of gender, age, atherosclerotic vein disease, urine pH and density, leukocyte count, lymphocyte count, neutrophil count (NEU), platelet count, mean platelet volume (MPV), neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), stone volume, HU, and obesity. RESULTS: The mean Hgb variation was identified as 2.1 (standard deviation: 1.6). There were positive, significant, and weak correlations between the Hgb variation with NEU (P=0.019), MPV (P=0.000), NLR (P=0.005), stone volume (P=0.041) and HU (P=0.024) values. There was a negative significant and weak correlation between Hgb variation and PLT (P=0.022). No effects at significant levels were identified for gender (P=0.078), presence of atheroma plaque (P=0.949), obesity (P=0.869), age (P=0.686), urine pH (P=0.746), urine density (P=0.421), and PLR (P=0.855) on Hgb variations. CONCLUSION: In addition to HU and stone volume, NEU count, MPV, NLR and PLT count may be used as independent risk factors to predict blood loss during PNL.


Asunto(s)
Nefrolitotomía Percutánea , Placa Aterosclerótica , Adulto , Masculino , Humanos , Femenino , Nefrolitotomía Percutánea/efectos adversos , Nefrolitotomía Percutánea/métodos , Estudios Retrospectivos , Placa Aterosclerótica/etiología , Factores de Riesgo , Hemorragia/etiología , Obesidad
7.
Eur Rev Med Pharmacol Sci ; 26(12): 4258-4267, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35776025

RESUMEN

OBJECTIVE: Intensive care units (ICU) are tasked with critical care and treatment with a view to improving prognosis. The Acute Physiology and Chronic Health Evaluation II (APACHE II) is one of the most commonly used scoring systems to predict prognosis. In this context, the objective of this study is to evaluate the prognostic value of Red Cell Distribution Width (RDW), Neutrophil-Lymphocyte ratio (NLR), and C-reactive protein to albumin ratio (CAR) in predicting the prognosis and mortality in patients admitted to the ICU. PATIENTS AND METHODS: The RDW, NLR, and CAR values and APACHE II scores of patients admitted into an ICU, where heterogeneous groups of patients are usually treated, were recorded, categorized based on survival status, and investigated for any correlation between surviving patients' mortality and length of stay (LoS) in ICU and the said parameters. RESULTS: The ICU mortality among the 2,147 patients included in the study was 43.2%. The most common diagnosis of the patients admitted to the ICU was sepsis. The RDW, NLR, and CAR values and APACHE II scores of the deceased patients were significantly higher than those of the survived patients. There was a significant correlation between LoS in ICU and the said parameters in the positive direction in the survived group only. The APACHE II score had the highest prognostic value in predicting mortality, followed by RDW, CAR, and NLR values in descending order. CONCLUSIONS: Among the parameters investigated in this study, RDW had the highest prognostic value in predicting the prognosis and mortality. Hence, it may be incorporated into or used alongside the APACHE II scoring system to predict patient outcomes with higher accuracy. However, further randomized controlled studies are needed to determine the cut-off values in predicting the prognosis and mortality.


Asunto(s)
Índices de Eritrocitos , Neutrófilos , APACHE , Cuidados Críticos , Mortalidad Hospitalaria , Humanos , Unidades de Cuidados Intensivos , Linfocitos , Pronóstico , Estudios Retrospectivos
8.
Viruses ; 14(6)2022 05 24.
Artículo en Inglés | MEDLINE | ID: mdl-35746605

RESUMEN

The COVID-19 pandemic began in 2019, but it is still active. The development of an effective vaccine reduced the number of deaths; however, a treatment is still needed. Here, we aimed to inhibit viral entry to the host cell by inhibiting spike (S) protein cleavage by several proteases. We developed a computational pipeline to repurpose FDA-approved drugs to inhibit protease activity and thus prevent S protein cleavage. We tested some of our drug candidates and demonstrated a decrease in protease activity. We believe our pipeline will be beneficial in identifying a drug regimen for COVID-19 patients.


Asunto(s)
COVID-19 , SARS-CoV-2 , Antivirales/farmacología , Evaluación Preclínica de Medicamentos , Reposicionamiento de Medicamentos , Humanos , Simulación del Acoplamiento Molecular , Péptido Hidrolasas , Glicoproteína de la Espiga del Coronavirus/metabolismo , Internalización del Virus
9.
Genes (Basel) ; 13(2)2022 01 25.
Artículo en Inglés | MEDLINE | ID: mdl-35205266

RESUMEN

Formation of Ras multimers, including dimers and nanoclusters, has emerged as an exciting, new front of research in the 'old' field of Ras biomedicine. With significant advances made in the past few years, we are beginning to understand the structure of Ras multimers and, albeit preliminary, mechanisms that regulate their formation in vitro and in cells. Here we aim to synthesize the knowledge accrued thus far on Ras multimers, particularly the presence of multiple globular (G-) domain interfaces, and discuss how membrane nanodomain composition and structure would influence Ras multimer formation. We end with some general thoughts on the potential implications of Ras multimers in basic and translational biology.


Asunto(s)
Transducción de Señal , Proteínas ras , Membrana Celular/metabolismo , Procesamiento Proteico-Postraduccional , Proteínas ras/genética , Proteínas ras/metabolismo
10.
Acta Endocrinol (Buchar) ; 18(3): 294-300, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36699178

RESUMEN

Objective: Both obesity and periodontal diseases are significant diseases that affect the quality of life. Recent studies have focused on the relationship between obesity and periodontal disease. The aim of this study is to determine the pathophysiological relationship between obesity and periodontal disease by evaluating the clinical periodontal parameters and oxidative status. Subjects and Methods: The study included 80 individuals divided into four groups including 20 individuals in each group as following; periodontally healthy patients with normal weight, (NH), patients with chronic periodontitis and normal weight (NCP), periodontally healthy patients with obesity (OH) and patients with chronic periodontitis and obesity (OCP). Clinical periodontal parameters were recorded, and serum, saliva and gingival crevicular fluid (GCF) samples were obtained. Local and systemic levels of total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI) were assessed biochemically. Results: No statistically significant difference was found among the groups regarding TAS, TOS and OSI values in serum and saliva samples (p>0.05). GCF-TAS values in NH group were statistically significantly higher compared with other groups (p<0,05) . GCF TOS values increased in obese groups (OH, OCP) compared with non-obese groups (NH, NCP) (p<0.05). Our results suggest that obesity and chronic periodontitis do not effect oxidant/antioxidant levels in serum and saliva. Conclusions: Many factors such as daily living conditions of the individual, stress and nutritional habits TAS and TOS levels of the individual may affect oxidative stress parameters. However, these factors could not be standardized in the study.

11.
Bratisl Lek Listy ; 122(12): 912-917, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34904854

RESUMEN

OBJECTIVES: This study aimed to investigate the wound healing activity of liposomal Carpobrotus edulis powder extract (CEPE) formulation on incisional and excisional wounds in rat. BACKGROUND: In the event of any damage, the damaged tissue undergoes a process of regenerating itself, which is called wound healing. METHODS: Centella asiatica extract (CAE) was used as the reference molecule in the study. The wound healing process was tested by using the excisional and incisional wound model. On the 12th day of the study, maximum stress, stress, % of elongation values were evaluated in the incisional wound. Also; histological parameters and macroscopic photographic analyses were evaluated in the excisional wound. RESULTS: In the photo evaluations, the improvement was more prominent in both CAE and CEPE groups than in the control group. Histological evaluation showed that CEPE group had significant wound healing activity compared to the control and CAE groups. Axial tensile-elongation experiments in incisional wound tissue show that there was no significant difference between CAE and CEPE groups. CONCLUSION: Liposomal formulations of C.edulis extract were found to have positive effects on the healing process, both on excisional and incisional wound tissues (Tab. 2, Fig. 3, Ref. 30).


Asunto(s)
Piel , Cicatrización de Heridas , Animales , Extractos Vegetales/farmacología , Ratas
12.
EBioMedicine ; 73: 103646, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34689087

RESUMEN

BACKGROUND: Senescent cells accumulate in tissues over time as part of the natural ageing process and the removal of senescent cells has shown promise for alleviating many different age-related diseases in mice. Cancer is an age-associated disease and there are numerous mechanisms driving cellular senescence in cancer that can be detrimental to recovery. Thus, it would be beneficial to develop a senolytic that acts not only on ageing cells but also senescent cancer cells to prevent cancer recurrence or progression. METHODS: We used molecular modelling to develop a series of rationally designed peptides to mimic and target FOXO4 disrupting the FOXO4-TP53 interaction and releasing TP53 to induce apoptosis. We then tested these peptides as senolytic agents for the elimination of senescent cells both in cell culture and in vivo. FINDINGS: Here we show that these peptides can act as senolytics for eliminating senescent human cancer cells both in cell culture and in orthotopic mouse models. We then further characterized one peptide, ES2, showing that it disrupts FOXO4-TP53 foci, activates TP53 mediated apoptosis and preferentially binds FOXO4 compared to TP53. Next, we show that intratumoural delivery of ES2 plus a BRAF inhibitor results in a significant increase in apoptosis and a survival advantage in mouse models of melanoma. Finally, we show that repeated systemic delivery of ES2 to older mice results in reduced senescent cell numbers in the liver with minimal toxicity. INTERPRETATION: Taken together, our results reveal that peptides can be generated to specifically target and eliminate FOXO4+ senescent cancer cells, which has implications for eradicating residual disease and as a combination therapy for frontline treatment of cancer. FUNDING: This work was supported by the Cancer Early Detection Advanced Research Center at Oregon Health & Science University.


Asunto(s)
Antineoplásicos/química , Proteínas de Ciclo Celular/química , Diseño de Fármacos , Factores de Transcripción Forkhead/química , Modelos Moleculares , Péptidos/química , Senoterapéuticos/química , Proteína p53 Supresora de Tumor/química , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Proteínas de Ciclo Celular/metabolismo , Senescencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Femenino , Factores de Transcripción Forkhead/metabolismo , Humanos , Masculino , Melanoma , Ratones , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Péptidos/farmacología , Conformación Proteica , Senoterapéuticos/farmacología , Relación Estructura-Actividad , Proteína p53 Supresora de Tumor/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
13.
Arq. bras. oftalmol ; 84(3): 235-240, May-June 2021. tab
Artículo en Inglés | LILACS | ID: biblio-1248975

RESUMEN

ABSTRACT Purposes: To evaluate the optical coherence tomography angiography findings in patients with Behçet disease with and without ocular involvement. Methods: A total of 40 patients with Behçet disease and 30 healthy controls were enrolled in the study. Retinal vessel density in the superficial capillary plexus and deep capillary plexus, foveal avascular zone area and perimeter, acirculatory index, foveal density, and nonflow area in the superficial retina were automatically measured using the optical coherence tomography angiography software AngioVue and compared between the groups. Results: The mean parafoveal and perifoveal vessel densities in the superficial capillary plexus and deep capillary plexus and foveal density were significantly lower in the eyes with Behçet uveitis compared to the eyes without Behçet uveitis and eyes of the healthy controls. In the eyes with Behçet uveitis, logMAR visual acuity showed a moderate correlation with parafoveal and perifoveal vessel densities and foveal density (r=-0.43, p=0.006; r=-0.62, p<0.001; r=-0.42, p=0.008; respectively). Conclusion: Behçet disease with posterior uveitis was associated with significant perifoveal and parafoveal vascular decrements in the superficial and deep retina.(AU)


RESUMO Objetivo: Avaliar achados de angiografia por tomografia de coerência óptica em pacientes com doença de Behçet com e sem acometimento ocular. Métodos: Foram incluídos 40 pacientes com doença de Behçet e 30 controles saudáveis. A densidade vascular retiniana nos plexos capilares superficial e profundo, a zona avascular foveal, o índice de circularidade, a densidade foveal e a área sem fluxo da retina superficial foram medidos automaticamente, através do software AngioVue para angiografia por tomografia de coerência óptica, e comparados entre os grupos. Resultados: A densidade vascular parafoveal e perifoveal média nos plexos capilares superficial e profundo, bem como a densidade foveal, foram significativamente menores nos olhos com uveíte de Behçet em comparação com os olhos sem uveíte de Behçet e os olhos dos controles saudáveis. Nos olhos com uveíte de Behçet, a acuidade visual logMAR mostrou correlação moderada com a densidade vascular parafoveal e perifoveal e com a densidade foveal (respectivamente, r=-0,43, p=0,006; r=-0,62, p<0,001; e r=-0,42, p = 0,008). Conclusão: A doença de Behçet com uveíte posterior foi associada a decréscimos significativos da vascularização perifoveal e parafoveal na retina superficial e profunda.(AU)


Asunto(s)
Humanos , Uveítis/patología , Angiografía/instrumentación , Síndrome de Behçet/fisiopatología , Tomografía de Coherencia Óptica/instrumentación , Fóvea Central/irrigación sanguínea
14.
Arq Bras Oftalmol ; 84(3): 235-240, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33567020

RESUMEN

PURPOSES: To evaluate the optical coherence tomography angiography findings in patients with Behçet disease with and without ocular involvement. METHODS: A total of 40 patients with Behçet disease and 30 healthy controls were enrolled in the study. Retinal vessel density in the superficial capillary plexus and deep capillary plexus, foveal avascular zone area and perimeter, acirculatory index, foveal density, and nonflow area in the superficial retina were automatically measured using the optical coherence tomography angiography software AngioVue and compared between the groups. RESULTS: The mean parafoveal and perifoveal vessel densities in the superficial capillary plexus and deep capillary plexus and foveal density were significantly lower in the eyes with Behçet uveitis compared to the eyes without Behçet uveitis and eyes of the healthy controls. In the eyes with Behçet uveitis, logMAR visual acuity showed a moderate correlation with parafoveal and perifoveal vessel densities and foveal density (r=-0.43, p=0.006; r=-0.62, p<0.001; r=-0.42, p=0.008; respectively). CONCLUSION: Behçet disease with posterior uveitis was associated with significant perifoveal and parafoveal vascular decrements in the superficial and deep retina.


Asunto(s)
Síndrome de Behçet , Tomografía de Coherencia Óptica , Angiografía con Fluoresceína , Fóvea Central , Humanos , Vasos Retinianos
15.
West Indian med. j ; 69(7): 464-470, 2021. tab, graf
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1515708

RESUMEN

ABSTRACT Objective: To investigate the serum levels of a vascular endothelial growth factor (VEGF), an angiogenic factor and a soluble angiopoietin receptor Tie-2 (sTie-2) in patients with essential hypertension. Methods: In the present study 90 individuals (56 males and 34 females, mean age 48 ± 7 years) have been divided into 3 groups: 30 patients with hypertension, 30 healthy individuals with a family history of hypertension and 30 healthy individuals with no family history of hypertension. All individuals have been evaluated in terms of blood pressure and biochemical parameters. The levels of VEGF and Tie-2 receptor have been evaluated by using the enzyme-linked immunosorbent assay method. Results: The findings suggested that the serum VEGF, sTie-2 receptor, low-density lipoprotein and triglycerides levels in the hypertensive patients were significantly higher than those in the control group (p < 0.05). However, the level of high-density lipoprotein cholesterol in the patients was significantly lower than in those in the control group (p < 0.05). In correlation analysis, a positive correlation was found statistically significant between the values of VEGF and sTie-2 (r = 0.405, p = 0.026). Conclusion: As a result of this study, our data indicate that serum levels of VEGF and Tie-2 receptor may be related to the primary hypertension. This study could inspire to further studies to explore the roles of VEGF and Tie-2 receptor in essential hypertension.

16.
J Mol Biol ; 432(4): 1199-1215, 2020 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-31931009

RESUMEN

Ras recruits and activates effectors that transmit receptor-initiated signals. Monomeric Ras can bind Raf; however, Raf's activation requires dimerization, which can be facilitated by Ras dimerization. Previously, we showed that active K-Ras4B dimerizes in silico and in vitro through two major interfaces: (i) ß-interface, mapped to Switch I and effector-binding regions, (ii) α-interface at the allosteric lobe. Here, we chose constitutively active K-Ras4B as our control and two double mutants (K101D and R102E; and R41E and K42D) in the α- and ß-interfaces. Two of the mutations are from The Cancer Genome Atlas (TCGA) and the Catalogue Of Somatic Mutations In Cancer (COSMIC) data sets. R41 and R102 are found in several adenocarcinomas in Ras isoforms. We performed site-directed mutagenesis, cellular localization experiments, and molecular dynamics (MD) simulations to assess the impact of the mutations on K-Ras4B dimerization and function. α-interface K101D/R102E double mutations reduced dimerization but only slightly reduced downstream phosphorylated extracellular signal-regulated kinase (ERK) (pERK) levels. While ß-interface R41E/K42D double mutations did not interfere with dimerization, they almost completely blocked K-Ras4B-mediated ERK phosphorylation. Both double mutations increased downstream phosphorylated Akt (pAkt) levels in cells. Changes in pERK and pAkt levels altered ERK- and Akt-regulated gene expressions, such as EGR1, JUN, and BCL2L11. These results underscore the role of the α-interface in K-Ras4B homodimerization and the ß-surface in effector binding. MD simulations highlight that the membrane and hypervariable region (HVR) interact with both α- and ß-interfaces of K-Ras4B mutants, respectively, inhibiting homodimerization and probably effector binding. Mutations at both interfaces interfered with mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase signaling but in different forms and extents. We conclude that dimerization is not necessary but enhances downstream MAPK signaling.


Asunto(s)
Proteínas Quinasas Activadas por Mitógenos/química , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas p21(ras)/química , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Secuencia de Aminoácidos , Transferencia Resonante de Energía de Fluorescencia , Células HEK293 , Humanos , Proteínas Quinasas Activadas por Mitógenos/genética , Simulación de Dinámica Molecular , Mutación/genética , Fosfatidilinositol 3-Quinasas/química , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación , Unión Proteica , Multimerización de Proteína , Estructura Secundaria de Proteína , Proteínas Proto-Oncogénicas c-akt/química , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Transducción de Señal/genética , Transducción de Señal/fisiología , Proteínas ras/química , Proteínas ras/genética , Proteínas ras/metabolismo
17.
J Laryngol Otol ; 133(9): 810-813, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31434591

RESUMEN

OBJECTIVE: This prospective study aimed to evaluate the relationship between serum ischaemia-modified albumin levels and Bell's palsy severity. METHODS: The study included 30 patients diagnosed with Bell's palsy and 30 healthy individuals. The patients were separated into three disease severity groups (grades 2, 3 and 4) according to House-Brackmann classification. Blood samples were collected from all participants and the results compared between groups. RESULTS: Significant differences in serum ischaemia-modified albumin were found between the study and control groups (p < 0.001); values were significantly higher in the study group than in the control group. CONCLUSION: The significantly higher levels of serum ischaemia-modified albumin in the study group suggest that Bell's palsy pathogenesis is associated with oxidative stress.

18.
Transplant Proc ; 51(4): 1086-1088, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-31101176

RESUMEN

AIM: The diagnosis and management of multiple renal arteries and veins have gained importance with the increasing number of kidney transplantations and improved techniques in interventional radiology and vascular reconstructions. The aim of this study is to define and to detect the rate of multiple renal arteries and veins in our living kidney transplant donors coming from all parts of our country. METHODS: Abdominal computed tomography angiogram findings of 878 kidney transplant donors were analyzed. The presence and the distribution of multiple renal arteries and veins in donors coming from 7 geographic regions in Turkey were noted. RESULTS: The presence of multiple renal arteries was observed in 34% (48/141) of patients in the Marmara Region, 36.7% (79/215) of patients in the Black Sea Region, 37.2% (64/172) of patients in the Central Anatolia Region and 36.1% (30/83) of patients in the Southeastern Anatolia Region. The highest incidences of multiple renal arteries were observed in the Mediterranean and Aegean regions, affecting 40% (32/80) and 41.9% (26/62) of patients, respectively, while East Anatolia was found to have the lowest incidence, affecting 28% (35/125) of patients. The incidence of multiple renal veins also varied across regions. The highest incidence was observed in the Central Anatolia Region, where 23.3% (40/172) of patients were affected; the lowest was seen in the Aegean Region, where 11.3% (7/62) of patients were affected. In Turkey as a whole, 35.8% (314/878) of patients presented with multiple renal arteries, while the rate of multiple renal veins was found to be 19% (167/878) among our donors. CONCLUSIONS: As 80% of the kidney transplantations performed in Turkey involve living donors, we think it will be useful to have knowledge of not only the presence of multiple renal arteries and veins, but also the distribution of this feature throughout the different regions of the country.


Asunto(s)
Anomalías Cardiovasculares/epidemiología , Trasplante de Riñón , Donadores Vivos , Arteria Renal/anomalías , Venas Renales/anomalías , Trasplantes/anomalías , Adulto , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Turquía/epidemiología
19.
Transplant Proc ; 51(4): 1190-1192, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30982642

RESUMEN

A blue kidney, although very rare, can be encountered upon a live kidney donor. Literature has shown hemosiderin deposits, lipofuscin pigment, and melanosis as possible reasons. We report on a 37-year-old woman who wished to donate a kidney to her husband. The donor's preoperative biochemistry and imaging tests showed normal renal function. During the laparoscopic left kidney nephrectomy, the kidney was observed to be blue in color. Perioperatively, Doppler ultrasonography was used to rule out vascular reasons, and a wedge biopsy was performed. The other kidney was also explored, and it turned out to be blue as well. Histopathological analysis showed melanosis in the tubules without malignity or pathologic changes in the glomeruli, the interstitium, or the vessels. Even though some causes of blue kidney may result in impairment of the renal function, after the necessary tests show no signs of malignity and functional impairment, a blue-colored kidney may be suitable for transplantation.


Asunto(s)
Trasplante de Riñón , Donadores Vivos , Melanosis , Trasplantes/patología , Adulto , Biopsia , Femenino , Humanos , Riñón/patología , Trasplante de Riñón/métodos
20.
Biotech Histochem ; 94(3): 180-188, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30409033

RESUMEN

Laurocerasus officinalis Roem. (syn: Prunus laurocerasus L.) is a member of Rosaceae family. We investigated the antimicrobial and antioxidant activity of L. officinalis Roem in wound healing both in vivo and in vitro using an excisional wound model model in mice. We used four groups of eight mice as follows: untreated (control), empty gel, extract + gel (L. officinalis + gel), and Madecassol® groups. All treatments were applied topically once daily. The scar area, percentage wound closure and epithelization time were measured. L. officinalis promoted wound healing and increased granulation tissue, epidermal regeneration and angiogenesis. L. officinalis extract, which is known for its antioxidant and antimicrobial activities, may be useful for promoting wound healing.


Asunto(s)
Extractos Vegetales/farmacología , Rosaceae/química , Cicatrización de Heridas/efectos de los fármacos , Animales , Antibacterianos/química , Antibacterianos/farmacología , Metanol , Ratones , Ratones Endogámicos BALB C , Extractos Vegetales/química
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