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1.
Heliyon ; 10(3): e24959, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38317974

RESUMEN

This study provides a general observation of the status of naturally occurring radioactive materials (NORMs) distribution in mining and industrial areas of Ghana in order to establish regional and national data on NORMs. The study includes data on radioactivity concentrations of U-238, Th-232, and K-40 in soils and for water concentrations of Ra-226, Th-228, and K-40 from various mining, oil, and gas communities, as well as water sources used for crop farming and farmlands. The average activity concentrations of U-238, Th-232, and K-40 in the soil samples were found to be 59 ± 16 Bq/kg, 48 ± 15 Bq/kg, and 286 ± 57 Bq/kg, respectively. The average concentration of Ra-226, Th-228, and K-40 in the water samples were found to be 1.62 ± 0.33 Bq/L, 2.08 ± 0.53 Bq/L, and 22.36 ± 3.44 Bq/L, respectively. The estimated average annual effective doses from external and internal exposure pathways in soil and water samples were 0.09 mSv/y and 0.54 mSv/y, respectively. The total annual effective dose resulting from both exposure pathways was calculated to be 0.63 mSv/y, which is below the 1 mSv/y dose limit recommended by the International Commission on Radiological Protection (ICRP) for controlling public radiation exposure. Based on the radiological hazard indices, the majority of the soil samples were found to be suitable as building materials as their respective indices were below the limits except for two sample locations and the sludge and scale samples. The average Excess Lifetime Cancer Risk (ELCR) value of the water samples was 1.6 times greater than the recommended value of 1.16 × 10-3, presenting a relatively higher risk to the public of developing cancer. No significant regional differences in the levels of radioactive elements. The regression models demonstrate strong interrelationships between the studied elements, with high R-squared values suggesting a predictable nature of one element's concentration based on others.

2.
Int J Cardiovasc Imaging ; 40(2): 307-319, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37935940

RESUMEN

In chronic kidney disease (CKD), as in IgA nephropathy (IgAN), cardiovascular (CV) mortality and morbidity are many times higher than in the general population, and diastolic dysfunction (LVDD) has prognostic significance as well. Tissue Doppler Echocardiography (TDI) is another method for measuring myocardial contractility and determining diastolic dysfunction. 79 IgAN patients (age 46 ± 11 years) with CKD stages 1-3 were investigated and followed for 70 ± 28.7 months. Doppler echocardiography was used to measure the E (early) and A (late) waves, as well as the E wave deceleration time (EDT) during mitral inflow. TDI was used to measure early (Ea) and late (Aa) diastolic velocities (lateral and septal basal wall fragment average). From these, we calculated the E/Ea and Ea/Aa ratios. The primary combined endpoints were total mortality, major CV events, and end-stage renal disease, and the secondary endpoints were cardiovascular or renal (eGFR decreased below 15 ml/min/1.73 m2 or renal replacement therapy was started). Patients with decreased Ea (< 13 cm/s) had significantly more endpoints (20/42 vs. 3/37; p = 0.001) than patients with higher Ea (≥ 13 cm/s). The secondary renal endpoints were also significantly higher (p = 0.004). In a multivariate model, the eGFR showed independent correlation with the E/A ratio (r = 0.466; p < 0.01), EDT (r = - 0.270; p < 0.01), Ea/Aa ratio (r = 0.455; p < 0.01), and decreased Ea (r = 0.544; p < 0.01). Independent factors influencing Ea were only EDT by uni- and multivariate regression but age and albuminuria by logistic regression. Decreased Ea measured by TDI seems to be an eligible factor to predict the prognosis of IgA nephropathy. The decreased Ea may be a helpful parameter to identify high-risk CKD patients.


Asunto(s)
Glomerulonefritis por IGA , Fallo Renal Crónico , Disfunción Ventricular Izquierda , Humanos , Adulto , Persona de Mediana Edad , Pronóstico , Glomerulonefritis por IGA/diagnóstico por imagen , Valor Predictivo de las Pruebas , Ecocardiografía , Diástole
3.
Sci Rep ; 13(1): 13611, 2023 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-37604958

RESUMEN

Recently, interest in measuring the concentration of 220Rn in air has increased greatly following the development of standards and the calibration of monitoring instruments. In this study, a 220Rn calibration chamber was designed and developed at the Institute of Radiochemistry and Radioecology (RRI) based on the computational fluid dynamics (CFD) method implemented in ANSYS Fluent 2020 R1 code at the University of Pannonia in Hungary. The behavior of 220Rn and its spatial distribution inside the 220Rn calibration chamber at RRI were investigated at different flow rates. The 220Rn concentration was close to homogeneous under higher flow regimes due to thorough mixing of the gas inside the chamber. Predictions based on CFD simulations were compared with experimentally measured transmission factors (Cout/Cin). The spatial distribution of 220Rn was dependent on the flow rate and the positions of the inlet and outlet. Our results clearly demonstrate the suitability of the 220Rn calibration chamber at RRI for calibrating monitoring instruments. Furthermore, the CFD-based predictions were in good agreement with the results obtained at higher flow rates using experimental and analytical models according to the relative deviation, with a maximum of approximately 9%.

4.
J Environ Radioact ; 265: 107224, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37356351

RESUMEN

Prediction of areas with elevated natural radiation is fundamental for the prevention of human exposure. Soil gas radon activity concentration and soil gas permeability are predictive parameters for the radon potential, which has great importance in areas where future urban development is planned. In this study, the soil gas radon equilibrium concentration (C∞) and soil gas permeability (K) were estimated through the application of theoretical and empirical models found in the literature. These models apply soil properties as input parameters. Using already existing soil parameters to predict the radon potential of an area would be useful in avoiding direct field measurements. Therefore, in this study, we examined whether the estimated soil gas radon activity concentration and soil gas permeability values match the values measured in the field. The soil gas radon activity concentration estimated by two theoretical models is about 50% of the measured value in the studied area. This underestimation can be attributed to the assumption that the radon activity concentration measured in the field depends only on soil parameters and the models do not take into account the underlying bedrock. Additionally, these models neglect the radon transport by advection and consider only the radon availability and migration in homogeneous media. Furthermore, they do not count certain characteristics of the soil that can be relevant, e.g. organic matter and clay content in the soil. To investigate more in detail such soil characteristics, seven samples located roughly along the slope, were selected to determine the soil chemical composition by ICP-MS. Evaluating the physical and chemical properties of the soil, it was found that the sampling sites with pH < 8 (low calcium content) the preferential adsorption was a dominant process. This causes radium enrichment in organic matter and clay, which directly influence the soil gas radon activity concentration. At pH > 8, radium is no longer preferentially adsorbed on organic matter but continues to be adsorbed on clays albeit this process is weak because radium competes with calcium cations. Also, there are other factors that may affect radon emanation in soil such as radium concentration and distribution, porosity and water content. In contrast, empirical model of soil gas permeability overestimates the measured value in the study area by an order of magnitude. A new model was made by modifying the previously proposed one, which can be used as a guide for the estimation of the median value of soil gas permeability in granitic areas, but not as an accurate predictor due to the lack of correlation between the estimated and measured values.


Asunto(s)
Monitoreo de Radiación , Radio (Elemento) , Radón , Contaminantes Radiactivos del Suelo , Humanos , Radón/análisis , Suelo/química , Arcilla , Radio (Elemento)/análisis , Calcio , Contaminantes Radiactivos del Suelo/análisis , Permeabilidad
5.
Int J Mol Sci ; 24(9)2023 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-37175806

RESUMEN

Autophagy (cellular self-degradation) plays a major role in maintaining the functional integrity (homeostasis) of essentially all eukaryotic cells. During the process, superfluous and damaged cellular constituents are delivered into the lysosomal compartment for enzymatic degradation. In humans, age-related defects in autophagy have been linked to the incidence of various age-associated degenerative pathologies (e.g., cancer, neurodegenerative diseases, diabetes, tissue atrophy and fibrosis, and immune deficiency) and accelerated ageing. Muscle mass decreases at detectable levels already in middle-aged patients, and this change can increase up to 30-50% at age 80. AUTEN-67 and -99, two small-molecule enhancers of autophagy with cytoprotective and anti-ageing effects have been previously identified and initially characterized. These compounds can increase the life span in wild-type and neurodegenerative model strains of the fruit fly Drosophila melanogaster. Adult flies were treated with these AUTEN molecules via feeding. Fluorescence and electron microscopy and Western blotting were used to assess the level of autophagy and cellular senescence. Flying tests were used to measure the locomotor ability of the treated animals at different ages. In the current study, the effects of AUTEN-67 and -99 were observed on striated muscle cells using the Drosophila indirect flight muscle (IFM) as a model. The two molecules were capable of inducing autophagy in IFM cells, thereby lowering the accumulation of protein aggregates and damaged mitochondria, both characterizing muscle ageing. Furthermore, the two molecules significantly improved the flying ability of treated animals. AUTEN-67 and -99 decrease the rate at which striated muscle cells age. These results may have a significant medical relevance that could be further examined in mammalian models.


Asunto(s)
Drosophila , Músculo Estriado , Animales , Humanos , Persona de Mediana Edad , Anciano de 80 o más Años , Drosophila melanogaster , Envejecimiento , Autofagia , Mamíferos
6.
Int J Mol Sci ; 24(6)2023 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-36982924

RESUMEN

A new flexible germacranolide (1, lobatolide H) was isolated from the aerial parts of Neurolaena lobata. The structure elucidation was performed by classical NMR experiments and DFT NMR calculations. Altogether, 80 theoretical level combinations with existing 13C NMR scaling factors were tested, and the best performing ones were applied on 1. 1H and 13C NMR scaling factors were also developed for two combinations utilizing known exomethylene containing derivatives, and the results were complemented by homonuclear coupling constant (JHH) and TDDFT-ECD calculations to elucidate the stereochemistry of 1. Lobatolide H possessed remarkable antiproliferative activity against human cervical tumor cell lines with different HPV status (SiHa and C33A), induced cell cycle disturbance and exhibited a substantial antimigratory effect in SiHa cells.


Asunto(s)
Asteraceae , Sesquiterpenos , Humanos , Estructura Molecular , Asteraceae/química , Espectroscopía de Resonancia Magnética , Imagen por Resonancia Magnética , Sesquiterpenos/farmacología
7.
Ann Med Surg (Lond) ; 82: 104525, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36092857

RESUMEN

Introduction and importance: In the last few years, the novel coronavirus, named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), generated a large health care problem worldwide. Due to the immunomodulation effect of the virus the number of opportunistic infections has also increased. Case presentation: We present the unique case of a patient who was diagnosed with an actinomycotic liver abscess after coronavirus disease 2019 (COVID-19) without the presence of any chronic disease or mucosal injury. Clinical discussion: According to the results of the computer tomography (CT scan) and the liver biopsy, the patient was treated with antibiotics and ultrasound-guided drainage. Conclusion: With this case we would like to draw attention to the possible occurrence of liver abscesses caused by an opportunistic pathogen following COVID-19.

8.
Biol Futur ; 73(4): 375-384, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35731422

RESUMEN

Autophagy is a highly conserved self-degradation process of eukaryotic cells which is required for the effective elimination of damaged and unnecessary cytosolic constituents. Defects in the process can cause the intracellular accumulation of such damages, thereby leading to the senescence and subsequent loss of the affected cell. Defective autophagy hence is implicated in the development of various degenerative processes, including cancer, neurodegenerative diseases, diabetes, tissue atrophy and fibrosis, and immune deficiency, as well as in accelerated aging. The autophagic process is mediated by numerous autophagy-related (ATG) proteins, among which the ATG8/LC3/GABARAP (Microtubule-associated protein 1A/1B-light chain 3/Gammaaminobutyric acid receptor-associated protein) superfamily has a pivotal role in the formation and maturation of autophagosome, a key (macro) autophagic structure (the autophagosome sequesters parts of the cytoplasm which are destined for breakdown). While in the unicellular yeast there is only a single ATG8 protein, metazoan systems usually contain more ATG8 paralogs. ATG8 paralogs generally display tissue-specific expression patterns and their functions are not strictly restricted to autophagy. For example, GABARAP proteins also play a role in intracellular vesicle transport, and, in addition to autophagosome formation, ATG8 also functions in selective autophagy. In this review, we summarize the functional diversity of ATG8/LC3/GABARAP proteins, using tractable genetic models applied in autophagy research.


Asunto(s)
Familia de las Proteínas 8 Relacionadas con la Autofagia , Autofagia , Evolución Molecular , Animales , Autofagia/genética , Familia de las Proteínas 8 Relacionadas con la Autofagia/clasificación , Familia de las Proteínas 8 Relacionadas con la Autofagia/genética , Familia de las Proteínas 8 Relacionadas con la Autofagia/metabolismo , Transporte Biológico , Vesículas Transportadoras/metabolismo , Filogenia
9.
BMC Med Educ ; 22(1): 344, 2022 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-35513883

RESUMEN

BACKGROUND: Breast Cancer (BC) specialists need to acquire comprehensive knowledge, covering their own specialty and principles of related disciplines. Blended learning, the integration of online and face-to-face learning, is becoming more and more important in academic education and has added value during pandemics which limit face-to-face learning and residential training. In this context, the ESO-ULM Certificate of Competence in Breast Cancer (CCB) provides postgraduate multidisciplinary education and delivers an academic postgraduate title. The aim of this work is to investigate the degree of satisfaction of 42 participants to the first two editions of the programme and to assess if attending the programme entailed any professional gain. METHODS: An ad-hoc questionnaire was developed exploring 4 areas: participants' characteristics, administrative aspects, CCB Program syllabus and design, professional impact. RESULTS: The program was attractive for specialists of different disciplines from all over the world: > 90% of responders appreciated the curriculum set up and the quality of the teaching. Despite 64% of responders changed their clinical practice, only 33% could implement institutional changes. One third of the participants activated a collaboration with other colleagues and 64% used the CCB as a trigger to take part in other educational activities. Only 12% of the participants had the opportunity, after CCB, to visit other BC Units or to be involved in international research projects. More than half of the attendees profited from attending CCB in terms of promotions (16.7%), change of working institution (9.5%) or development of a more structured educational program at their home institutions (28.6%). CONCLUSIONS: Results provide interesting and stimulating considerations on the expectations and needs of training physicians and on what modern educational tools and formats can achieve. This paper can provide useful information to navigate through what the post-graduate training market is currently offering to develop a specific curriculum in modern multidisciplinary BC care but might not be applicable to other fields of multidisciplinary oncology.


Asunto(s)
Neoplasias de la Mama , Neoplasias de la Mama/terapia , Curriculum , Femenino , Humanos , Aprendizaje , Especialización , Encuestas y Cuestionarios
10.
NPJ Breast Cancer ; 8(1): 69, 2022 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-35637226
11.
Breast ; 63: 123-139, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35366506

RESUMEN

AIM: Demand for nipple- and skin- sparing mastectomy (NSM/SSM) with immediate breast reconstruction (BR) has increased at the same time as indications for post-mastectomy radiation therapy (PMRT) have broadened. The aim of the Oncoplastic Breast Consortium initiative was to address relevant questions arising with this clinically challenging scenario. METHODS: A large global panel of oncologic, oncoplastic and reconstructive breast surgeons, patient advocates and radiation oncologists developed recommendations for clinical practice in an iterative process based on the principles of Delphi methodology. RESULTS: The panel agreed that surgical technique for NSM/SSM should not be formally modified when PMRT is planned with preference for autologous over implant-based BR due to lower risk of long-term complications and support for immediate and delayed-immediate reconstructive approaches. Nevertheless, it was strongly believed that PMRT is not an absolute contraindication for implant-based or other types of BR, but no specific recommendations regarding implant positioning, use of mesh or timing were made due to absence of high-quality evidence. The panel endorsed use of patient-reported outcomes in clinical practice. It was acknowledged that the shape and size of reconstructed breasts can hinder radiotherapy planning and attention to details of PMRT techniques is important in determining aesthetic outcomes after immediate BR. CONCLUSIONS: The panel endorsed the need for prospective, ideally randomised phase III studies and for surgical and radiation oncology teams to work together for determination of optimal sequencing and techniques for PMRT for each patient in the context of BR.


Asunto(s)
Neoplasias de la Mama , Mamoplastia , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Femenino , Humanos , Mamoplastia/métodos , Mastectomía/métodos , Pezones , Estudios Prospectivos
12.
Cancers (Basel) ; 14(8)2022 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-35454902

RESUMEN

Due to its overexpression on the surface of prostate cancer (PCa) cells, the prostate stem cell antigen (PSCA) is a potential target for PCa diagnosis and therapy. Here we describe the development and functional characterization of a novel IgG4-based anti-PSCA antibody (Ab) derivative (anti-PSCA IgG4-TM) that is conjugated with the chelator DOTAGA. The anti-PSCA IgG4-TM represents a multimodal immunotheranostic compound that can be used (i) as a target module (TM) for UniCAR T cell-based immunotherapy, (ii) for diagnostic positron emission tomography (PET) imaging, and (iii) targeted alpha therapy. Cross-linkage of UniCAR T cells and PSCA-positive tumor cells via the anti-PSCA IgG4-TM results in efficient tumor cell lysis both in vitro and in vivo. After radiolabeling with 64Cu2+, the anti-PSCA IgG4-TM was successfully applied for high contrast PET imaging. In a PCa mouse model, it showed specific accumulation in PSCA-expressing tumors, while no uptake in other organs was observed. Additionally, the DOTAGA-conjugated anti-PSCA IgG4-TM was radiolabeled with 225Ac3+ and applied for targeted alpha therapy. A single injection of the 225Ac-labeled anti-PSCA IgG4-TM was able to significantly control tumor growth in experimental mice. Overall, the novel anti-PSCA IgG4-TM represents an attractive first member of a novel group of radio-/immunotheranostics that allows diagnostic imaging, endoradiotherapy, and CAR T cell immunotherapy.

13.
Eur J Neurol ; 29(6): 1663-1684, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35194889

RESUMEN

BACKGROUND AND PURPOSE: Despite the increasing number of reports on the spectrum of neurological manifestations of COVID-19 (neuro-COVID), few studies have assessed short- and long-term outcome of the disease. METHODS: This is a cohort study enrolling adult patients with neuro-COVID seen in neurological consultation. Data were collected prospectively or retrospectively in the European Academy of Neurology NEuro-covid ReGistrY ((ENERGY). The outcome at discharge was measured using the modified Rankin Scale and defined as 'stable/improved' if the modified Rankin Scale score was equal to or lower than the pre-morbid score, 'worse' if the score was higher than the pre-morbid score. Status at 6 months was also recorded. Demographic and clinical variables were assessed as predictors of outcome at discharge and 6 months. RESULTS: From July 2020 to March 2021, 971 patients from 19 countries were included. 810 (83.4%) were hospitalized. 432 (53.3%) were discharged with worse functional status. Older age, stupor/coma, stroke and intensive care unit (ICU) admission were predictors of worse outcome at discharge. 132 (16.3%) died in hospital. Older age, cancer, cardiovascular complications, refractory shock, stupor/coma and ICU admission were associated with death. 262 were followed for 6 months. Acute stroke or ataxia, ICU admission and degree of functional impairment at discharge were predictors of worse outcome. 65/221 hospitalized patients (29.4%) and 10/32 non-hospitalized patients (24.4%) experienced persisting neurological symptoms/signs. 10/262 patients (3.8%) developed new neurological complaints during the 6 months of follow-up. CONCLUSIONS: Neuro-COVID is a severe disease associated with worse functional status at discharge, particularly in older subjects and those with comorbidities and acute complications of infection.


Asunto(s)
COVID-19 , Neurología , Accidente Cerebrovascular , Estupor , Adulto , Anciano , COVID-19/complicaciones , Estudios de Cohortes , Coma , Humanos , Unidades de Cuidados Intensivos , Estudios Retrospectivos , SARS-CoV-2 , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/terapia
14.
Eur J Surg Oncol ; 48(11): 2338-2345, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35090797

RESUMEN

INTRODUCTION: Multimodal treatment of patients with advanced pelvic malignancies (APM) is challenging and surgical expertise is usually concentrated in highly specialised centres. Given significant regional variation in APM surgery, surgical training represents a cornerstone in standardising and future-proofing of this complex therapy. The aim of this study was to describe the availability and current satisfaction levels with surgical training for APM. MATERIAL AND METHODS: An online questionnaire was developed and distributed through the Redcap© platform with 32 questions addressing participant and institution demographics, and training in APM surgeries. The survey was electronically disseminated in 2021 to surgical networks across Europe including all specialities treating APM via the European Society of Surgical Oncology (ESSO). All statistical analysis were performed using R. RESULTS: The survey received 280 responses from surgeons across 49 countries, representing general surgery (36%), surgical oncology (30%), gynaeoncology (15%), colorectal surgery (14%) and urology (5%). Fifty-three percent of participants report performing >25 APM procedures/year. Respondents were departmental chiefs (12%), consultants (34%), specialist surgeons (40%) and fellows (15%). 34% were happy/very happy with their training with 70% satisfaction about their exposure to surgical procedures. Respondents reported a lack of standardised training (72%), monitoring tools (41%) and mentorship (56%). 57% rated attended courses as useful for training, while 80% rated visiting expert centres as useful. CONCLUSION: This study has identified a learning need for improved structured training in APM, with low current satisfaction levels with exposure to APM training. Organisations such as ESSO provide an important platform for visiting expert centres, courses, and structured training.


Asunto(s)
Neoplasias Pélvicas , Cirujanos , Oncología Quirúrgica , Urología , Humanos , Neoplasias Pélvicas/cirugía , Europa (Continente) , Urología/educación , Oncología Quirúrgica/educación , Encuestas y Cuestionarios
15.
Sci Rep ; 11(1): 24002, 2021 12 14.
Artículo en Inglés | MEDLINE | ID: mdl-34907289

RESUMEN

Cerenkov luminescence imaging (CLI) is a promising approach to image-guided surgery and pathological sampling. It could offer additional advantages when combined to whole-body isotope tomographies. We aimed to obtain evidence of its applicability in lymphoma patho-diagnostics, thus we decided to investigate the radiodiagnostic potential of combined PET or SPECT/CLI in an experimental, novel spontaneous high-grade B-cell lymphoma mouse model (Bc.DLFL1). We monitored the lymphoma dissemination at early stage, and at clinically relevant stages such as advanced stage and terminal stage with in vivo 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET)/magnetic resonance imaging (MRI) and 67Ga-citrate single photon emission computed tomography (SPECT)/MRI. In vivo imaging was combined with ex vivo high resolution CLI. The use of CLI with 18F-Fluorine (F-18) and 67Ga-Gallium isotopes in the selection of infiltrated lymph nodes for tumor staging and pathology was thus tested. At advanced stage, FDG PET/MRI plus ex vivo CLI allowed accurate detection of FDG accumulation in lymphoma-infiltrated tissues. At terminal stage we detected tumorous lymph nodes with SPECT/MRI and we could report in vivo detection of the Cerenkov light emission of 67Ga. CLI with 67Ga-citrate revealed lymphoma accumulation in distant lymph node locations, unnoticeable with only MRI. Flow cytometry and immunohistochemistry confirmed these imaging results. Our study promotes the combined use of PET and CLI in preclinical studies and clinical practice. Heterogeneous FDG distribution in lymph nodes, detected at sampling surgery, has implications for tissue pathology processing and it could direct therapy. The results with 67Ga also point to the opportunities to further apply suitable SPECT radiopharmaceuticals for CLI.


Asunto(s)
Fluorodesoxiglucosa F18/farmacología , Radioisótopos de Galio/farmacología , Mediciones Luminiscentes , Linfoma/diagnóstico por imagen , Neoplasias Experimentales/diagnóstico por imagen , Tomografía de Emisión de Positrones , Animales , Ratones , Ratones Endogámicos BALB C
16.
Pharmaceutics ; 13(12)2021 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-34959370

RESUMEN

Seven new germacranolides (1-3, 5-8), among them a heterodimer (7), and known germacranolide (4), eudesmane (9) and isodaucane (10) sesquiterpenes were isolated from the aerial parts of Neurolaena lobata. Their structures were determined by using a combination of different spectroscopic methods, including HR-ESIMS and 1D and 2D NMR techniques supported by DFT-NMR calculations. The enantiomeric purity of the new compounds was investigated by chiral HPLC analysis, while their absolute configurations were determined by TDDFT-ECD and OR calculations. Due to the conformationally flexible macrocycles and difficulties in assigning the relative configuration, 13C and 1H NMR chemical shift and ECD and OR calculations were performed on several stereoisomers of two derivatives. The isolated compounds (1-10) were shown to have noteworthy antiproliferative activities against three human cervical tumor cell line with different HPV status (HeLa, SiHa and C33A). Additionally, lobatolide C (6) exhibited substantial antiproliferative properties, antimigratory effect, and it induced cell cycle disturbance in SiHa cells.

18.
Autophagy ; 17(12): 4010-4028, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-33779490

RESUMEN

Myotubularin (MTM) and myotubularin-related (MTMR) lipid phosphatases catalyze the removal of a phosphate group from certain phosphatidylinositol derivatives. Because some of these substrates are required for macroautophagy/autophagy, during which unwanted cytoplasmic constituents are delivered into lysosomes for degradation, MTM and MTMRs function as important regulators of the autophagic process. Despite its physiological and medical significance, the specific role of individual MTMR paralogs in autophagy control remains largely unexplored. Here we examined two Drosophila MTMRs, EDTP and Mtmr6, the fly orthologs of mammalian MTMR14 and MTMR6 to MTMR8, respectively, and found that these enzymes affect the autophagic process in a complex, condition-dependent way. EDTP inhibited basal autophagy, but did not influence stress-induced autophagy. In contrast, Mtmr6 promoted the process under nutrient-rich settings, but effectively blocked its hyperactivation in response to stress. Thus, Mtmr6 is the first identified MTMR phosphatase with dual, antagonistic roles in the regulation of autophagy, and shows conditional antagonism/synergism with EDTP in modulating autophagic breakdown. These results provide a deeper insight into the adjustment of autophagy.Abbreviations: Atg, autophagy-related; BDSC, Bloomington Drosophila Stock Center; DGRC, Drosophila Genetic Resource Center; EDTP, Egg-derived tyrosine phosphatase; FYVE, zinc finger domain from Fab1 (yeast ortholog of PIKfyve), YOTB, Vac1 (vesicle transport protein) and EEA1 cysteine-rich proteins; LTR, LysoTracker Red; MTM, myotubularin; MTMR, myotubularin-related; PI, phosphatidylinositol; Pi3K59F, Phosphotidylinositol 3 kinase 59F; PtdIns3P, phosphatidylinositol-3-phosphate; PtdIns(3,5)P2, phosphatidylinositol-3,5-bisphosphate; PtdIns5P, phosphatidylinositol-5-phosphate; ref(2)P, refractory to sigma P; Syx17, Syntaxin 17; TEM, transmission electron microscopy; UAS, upstream activating sequence; Uvrag, UV-resistance associated gene; VDRC, Vienna Drosophila RNAi Center; Vps34, Vacuolar protein sorting 34.


Asunto(s)
Proteínas de Drosophila , Drosophila , Animales , Autofagia/genética , Drosophila/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Lisosomas/metabolismo , Mamíferos/metabolismo , Fosfatidilinositoles/metabolismo , Proteínas Tirosina Fosfatasas/genética , Proteínas Tirosina Fosfatasas/metabolismo
19.
Breast ; 57: 25-35, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33711697

RESUMEN

INTRODUCTION: The potential advantages of oncoplastic breast conserving surgery (BCS) have not been validated in robust studies that constitute high levels of evidence, despite oncoplastic techniques being widely adopted around the globe. There is hence the need to define the precise role of oncoplastic BCS in the treatment of early breast cancer, with consensual recommendations for clinical practice. METHODS: A panel of world-renowned breast specialists was convened to evaluate evidence, express personal viewpoints and establish recommendations for the use of oncoplastic BCS as primary treatment of unifocal early stage breast cancers using the GRADE approach. RESULTS: According to the results of the systematic review of literature, the panelists were asked to comment on the recommendation for use of oncoplastic BCS for treatment of operable breast cancer that is suitable for breast conserving surgery, with the GRADE approach. Based on the voting outcome, the following recommendation emerged as a consensus statement: Oncoplastic breast conserving surgery should be recommended versus standard breast conserving surgery for the treatment of operable breast cancer in adult women who are suitable candidates for breast conserving surgery (with very low certainty of evidence). DISCUSSION: This review has revealed a low level of evidence for most of the important outcomes in oncoplastic surgery with lack of any randomized data and absence of standard tools for evaluation of clinical outcomes and especially patients' values. Despite areas of controversy, about one-third (36%) of panel members expressed a strong recommendation in support of oncoplastic BCS. Presumably, this reflects a synthesis of views on the relative complexity of these techniques, associated complications, impact on quality of life and costs.


Asunto(s)
Neoplasias de la Mama/cirugía , Mastectomía Segmentaria , Neoplasias de la Mama/patología , Estudios Transversales , Femenino , Enfoque GRADE , Humanos , Estudios Prospectivos , Calidad de Vida
20.
Artículo en Inglés | MEDLINE | ID: mdl-33430080

RESUMEN

The determination of natural radionuclide concentrations plays an important role for assuring public health and in the estimation of the radiological hazards. This is especially true for high level radiation areas. In this study, 226Ra, 228Ra and 238U concentrations were measured in well waters surrounding eight of the high-level natural radiation areas in northern Vietnam. The 226Ra, 228Ra and 238U activity concentrations vary from <1.2 × 10-3-2.7 (0.46), <2.6 × 10-3-0.43 (0.07) and <38 × 10-3-5.32 Bq/L (0.50 of median), respectively. 226Ra and 238U isotopes in most areas are in equilibrium, except for the DT-Thai Nguyen area. The calculated radiological hazard indices are generally higher than WHO (World Health Organization) recommendations. Average annual effective dose and excess lifetime cancer risk values due to drinking well water range from to 130 to 540 µSv/year and 7.4 × 10-6 to 3.1 × 10-5, respectively.


Asunto(s)
Monitoreo de Radiación , Radio (Elemento) , Uranio , Contaminantes Radiactivos del Agua , Radiación de Fondo , Dosis de Radiación , Radio (Elemento)/análisis , Uranio/análisis , Vietnam , Contaminantes Radiactivos del Agua/análisis
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