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1.
Eur J Surg Oncol ; 50(6): 108050, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38498966

RESUMO

BACKGROUND: Isolated limb perfusion (ILP) is a well-established surgical procedure for the administration of high dose chemotherapy to a limb for the treatment of advanced extremity malignancy. Although the technique of ILP was first described over 60 years ago, ILP is utilised in relatively few specialist centres, co-located with tertiary or quaternary cancer centres. The combination of high dose cytotoxic chemotherapy and the cytokine tumour necrosis factor alpha (TNFα), mandates leakage monitoring to prevent potentially serious systemic toxicity. Since the procedure is performed at relatively few specialist centres, an ILP working group was formed with the aim of producing technical consensus guidelines for the procedure to streamline practice and to provide guidance for new centres commencing the technique. METHODS: Between October 2021 and October 2023 a series of face to face online and hybrid meetings were held in which a modified Delphi process was used to develop a unified consensus document. After each meeting the document was modified and recirculated and then rediscussed at subsequent meeting until a greater than 90% consensus was achieved in all recommendations. RESULTS: The completed consensus document comprised 23 topics in which greater than 90% consensus was achieved, with 83% of recommendations having 100% consensus across all members of the working group. The consensus recommendations covered all areas of the surgical procedure including pre-operative assessment, drug dosing and administration, perfusion parameters, hyperthermia, leakage monitoring and theatre logistics, practical surgical strategies and also post-operative care, response evaluation and staff training. CONCLUSION: We present the first joint expert-based consensus statement with respect to the technical aspects of ILP that can serve as a reference point for both existing and new centres in providing ILP.

2.
Chem Biodivers ; 21(4): e202400235, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38412304

RESUMO

Over the last decades, soft corals have been proven a rich source of biologically active compounds, featuring a wide range of chemical structures. Herein, we investigated the chemistry of an alcyonarian of the genus Lemnalia (Neptheidae), specimens of which were collected from the coral reefs near Al Lith, on the south-west coast of Saudi Arabia. A series of chromatographic separations led to the isolation of 31 sesquiterpenes, featuring mainly the nardosinane and neolemnane carbon skeletons, among which three (13, 14 and 28) are new natural products. The metabolites isolated in sufficient amounts were evaluated in vitro in human tumor and non-cancerous cell lines for a number of biological activities, including their cytotoxic, anti-inflammatory, anti-angiogenic, and neuroprotective activities, as well as for their effect on androgen receptor (AR)-regulated transcription. Among the tested metabolites, compound 12 showed comparable neuroprotective activity to the positive control N-acetylcysteine, albeit at a 10-fold lower concentration.


Assuntos
Antozoários , Antineoplásicos , Sesquiterpenos , Animais , Humanos , Arábia Saudita , Oceano Índico , Sesquiterpenos/química , Antozoários/química , Antineoplásicos/farmacologia , Antineoplásicos/metabolismo
3.
Eur J Cancer ; 190: 112949, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37453241

RESUMO

OBJECTIVE: The aim of this study was to investigate the response rates of different extremity soft-tissue sarcoma subtypes (eSTS) after isolated limb perfusion (ILP), based on an international multi-centre study. MATERIALS AND METHODS: The retrospective cohort comprised eSTS patients from 17 specialised ILP centres that underwent melphalan-based ILP, with or without recombinant human tumour necrosis factor (rhTNFα) (TM-ILP and M-ILP, respectively). Response was measured on imaging (magnetic resonance imaging) and/or clinical response, for which M-ILPs were excluded. RESULTS: A total of 1109 eSTS patients were included. The three most common histological subtypes were undifferentiated pleomorphic sarcoma (17%, n = 184), synovial sarcoma (16%, n = 175) and myxofibrosarcoma (8%, n = 87). rhTNFα was used in 93% (TM-ILP) and resulted in a significantly better overall response rate (ORR, p = 0.031) and complete responses (CR, p < 0.001) in comparison to M-ILP, without significant differences among histological subgroups. The ORR of TM-ILP was 68%, including 17% CR. Also, 80% showed progressive disease. Significantly higher response rates were shown for Kaposi sarcoma (KS) with 42% CR and 96% ORR (both p < 0.001), and significantly higher CR rates for angiosarcoma (AS, 45%, p < 0.001) and clear cell sarcoma (CCS, 31%, p = 0.049). ILP was followed by resection ≤ 6 months in 80% of the patients. The overall limb salvage rate was 88%, without significant differences among histological subgroups, but was significantly higher for ILP responders compared to non-responders (93% versus 76%, p < 0.001). CONCLUSION: ILP resulted in high response and LRS among all eSTS subtypes, however, with significant differences between subtypes with most promising results for KS, AS and CCS.


Assuntos
Sarcoma de Kaposi , Sarcoma , Neoplasias de Tecidos Moles , Adulto , Humanos , Estudos Retrospectivos , Quimioterapia do Câncer por Perfusão Regional/métodos , Sarcoma/patologia , Melfalan/uso terapêutico , Extremidades/patologia , Neoplasias de Tecidos Moles/patologia , Perfusão , Fator de Necrose Tumoral alfa , Antineoplásicos Alquilantes/uso terapêutico
4.
Environ Sci Pollut Res Int ; 30(26): 69150-69164, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37133655

RESUMO

Understanding the immediate impacts of oil spills is essential to recognizing their long-term consequences on the marine environment. In this study, we traced the early (within one week) signals of crude oil in seawater and plankton after a major oil spill in October 2019 in the Red Sea. At the time of sampling, the plume had moved eastward, but we detected significant signs of incorporation of oil carbon into the dissolved organic carbon pool, resulting in a 10-20% increase in the ultraviolet (UV) absorption coefficient (a254) of chromophoric dissolved organic matter (CDOM), elevated oil fluorescence emissions, and depletion of the carbon isotope composition (δ13C) of the seawater. The abundance of the picophytoplankton Synechococcus was not affected, but the proportion of low nucleic acid (LNA) bacteria was significantly higher. Moreover, specific bacterial genera (Alcanivorax, Salinisphaera, and Oleibacter) were enriched in the seawater microbiome. Metagenome-assembled genomes (MAGs) suggested that such bacteria presented pathways for growing on oil hydrocarbons. Traces of polycyclic aromatic hydrocarbons (PAHs) were also detected in zooplankton tissues, revealing the rapid entry of oil pollutants into the pelagic food web. Our study emphasizes the early signs of short-lived spills as an important aspect of the prediction of long-term impacts of marine oil spills.


Assuntos
Poluição por Petróleo , Petróleo , Hidrocarbonetos Policíclicos Aromáticos , Synechococcus , Poluentes Químicos da Água , Poluição por Petróleo/análise , Plâncton/metabolismo , Petróleo/análise , Oceano Índico , Água do Mar/microbiologia , Hidrocarbonetos Policíclicos Aromáticos/análise , Poluentes Químicos da Água/análise
5.
Exp Cell Res ; 426(2): 113523, 2023 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-36889572

RESUMO

Epithelial ovarian cancer (EOC) is the gynecological malignant tumor of poorest prognosis and higher mortality rate. Chemotherapy is the base of high-grade serous ovarian cancer (HGSOC) treatment; however, it favors the emergence of chemoresistance and metastasis. Thus, there is an urge to search for new therapeutic targets, such as proteins related to cellular proliferation and invasion. Herein, we investigated the expression profile of claudin-16 (CLDN16 protein and CLDN16 transcript) and its possible functions in EOC. In silico analysis of CLDN16 expression profile was performed using data extracted from GENT2 and GEPIA2 platforms. A retrospective study was carried out with 55 patients to evaluate the expression of CLDN16. The samples were evaluated by immunohistochemistry, immunofluorescence, qRT-PCR, molecular docking, sequencing, and immunoblotting assays. Statistical analyzes were performed using Kaplan-Meier curves, one-way ANOVA, Turkey posttest. Data were analyzed using GraphPad Prism 8.0. In silico experiments showed that CLDN16 is overexpressed in EOC. 80.0% of all EOC types overexpressed CLDN16, of which in 87% of the cases the protein is restricted to cellular cytoplasm. CLDN16 expression was not related to tumor stage, tumor cells differentiation status, tumor responsiveness to cisplatin, or patients' survival rate. When compared to data obtained from in silico analysis regarding EOC stage and degree of differentiation, differences were found in the former but not in the later, neither in survival curves. CLDN16 expression in HGSOC OVCAR-3 cells increased by 1.95-fold (p < 0.001), 2.32-fold (p < 0.001), and 6.57-fold (p < 0.001) via PKC, PI3K, and estrogen pathways, respectively. Altogether, our results suggest that despite the low number of samples included in our in vitro studies, adding to the expression profile findings, we provided a comprehensive study of CLDN16 expression in EOC. Therefore, we hypothesize that CLDN16 is a potential target in the diagnosis and treatment of the disease.


Assuntos
Neoplasias Epiteliais e Glandulares , Neoplasias Ovarianas , Feminino , Humanos , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Epitelial do Ovário/metabolismo , Linhagem Celular Tumoral , Estimativa de Kaplan-Meier , Simulação de Acoplamento Molecular , Neoplasias Ovarianas/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Estudos Retrospectivos , Proteína Quinase C/metabolismo
6.
J Mol Neurosci ; 72(7): 1500-1515, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35819636

RESUMO

Epilepsy is a neurological disease characterized by abnormal or synchronous brain activity causing seizures, which may produce convulsions, minor physical signs, or a combination of symptoms. These disorders affect approximately 65 million people worldwide, from all ages and genders. Seizures apart, epileptic patients present a high risk to develop neuropsychological comorbidities such as cognitive deficits, emotional disturbance, and psychiatric disorders, which severely impair quality of life. Currently, the treatment for epilepsy includes the administration of drugs or surgery, but about 30% of the patients treated with antiepileptic drugs develop time-dependent pharmacoresistence. Therefore, further investigation about epilepsy and its causes is needed to find new pharmacological targets and innovative therapeutic strategies. Pharmacoresistance is associated to changes in neuronal plasticity and alterations of GABAA receptor-mediated neurotransmission. The downregulation of GABA inhibitory activity may arise from a positive shift in GABAA receptor reversal potential, due to an alteration in chloride homeostasis. In this paper, we review the contribution of K+-Cl--cotransporter (KCC2) to the alterations in the Cl- gradient observed in epileptic condition, and how these alterations are coupled to the increase in the excitability.


Assuntos
Epilepsia , Simportadores , Cloretos/metabolismo , Feminino , Humanos , Masculino , Qualidade de Vida , Receptores de GABA-A/genética , Convulsões , Simportadores/genética
7.
Rev. cuba. med ; 61(2): e2625, abr.-jun. 2022. tab, graf
Artigo em Espanhol | LILACS, CUMED | ID: biblio-1408992

RESUMO

Introducción: El bienestar y la salud de cada uno de los trabajadores son primordiales en el Departamento de Salud Ocupacional de la Fundación Hospital Universitario Metropolitano. Es importante que el personal goce de un nivel de vida saludable para cumplir satisfactoriamente con todas sus obligaciones y las metas planeadas de la organización. Objetivo: Analizar los factores neuropsicológicos y de personalidad asociados en un grupo de personas que se han accidentado dos o más veces (poliaccidentados). Métodos: Se desarrolló un diseño metodológico de casos y controles. Se tomó como población las bases de datos del departamento de seguridad y salud en el trabajo, con 50 trabajadores accidentados en dos o más ocasiones (poliaccidentados). Se aplicaron como técnicas de recolección de datos la escala abreviada de inteligencia Reynolds (Rist) para apreciar el coeficiente de inteligencia de los sujetos y el cuestionario de personalidad de Cattell (16 Pf), que midió 16 factores primarios y cuatro secundarios. Se utilizó la Batería Neuropsicológica de Funciones Ejecutivas y Lóbulos Frontales (BANFE) para evaluar los factores neuropsicológicos. Resultados: fue procesados mediante el paquete estadístico Statistical package Social Science (Spss) versión 21.0 que permitió realizar la prueba de hipótesis para las variables estudiadas, se utilizó la prueba U de Mann Whitney, con un criterio alfa de 0,05 y un nivel de confianza del 95 por ciento. Conclusiones: El grupo de poliaccidentados presentó alteraciones en las áreas orbito-medial, ventromedial y dorso-laterales lo que los predispone a una mayor posibilidad de realizar actividades riesgosas y presentar menor consciencia del riesgo(AU)


Introduction: The well-being and health of each of the workers are paramount in the Department of Occupational Health at Fundación Hospital Universitario Metropolitano. It is important that the staff enjoy a healthy standard of living in order to satisfactorily fulfil all their obligations and the planned goals of the organization. Objective: To look at the neuropsychological and personality factors associated in a group of individuals who have been injured two or more times (poly-accidented). Methods: A case-control methodological design was developed. The databases of the Department of Labor Safety and Health were taken as the population, with 50 workers injured on two or more occasions (poly-accidents). The abbreviated Reynolds Intelligence Scale (Rist) was applied as data collection techniques to assess the intelligence coefficient of the subjects and Cattell personality questionnaire (16 Pf), to measured 16 primary factors and four secondary factors. The Neuropsychological Battery of Executive Functions and Frontal Lobes (BANFE) was used to evaluate neuropsychological factors. Results: They were processed using the Statistical Package Social Science (Spss) version 21.0 that allowed the hypothesis test to be carried out for the variables studied, Mann Whitney U test was used, with 0.05 alpha criterion and 95 percent level of confidence. Conclusions: The group of poly-accidented patients showed alterations in the orbito-medial, ventromedial and dorso-lateral areas, which predisposes them to greater possibility of carrying out risky activities and presenting less risk awareness(AU)


Assuntos
Humanos , Masculino , Feminino , Acidentes de Trabalho/psicologia , Fatores de Risco , Testes Neuropsicológicos/normas , Colômbia
8.
Front Cell Dev Biol ; 10: 788808, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35265608

RESUMO

The characterization, control, and reporting of environmental conditions in mammalian cell cultures is fundamental to ensure physiological relevance and reproducibility in basic and preclinical biomedical research. The potential issue of environment instability in routine cell cultures in affecting biomedical experiments was identified many decades ago. Despite existing evidence showing variable environmental conditions can affect a suite of cellular responses and key experimental readouts, the underreporting of critical parameters affecting cell culture environments in published experiments remains a serious problem. Here, we outline the main sources of potential problems, improved guidelines for reporting, and deliver recommendations to facilitate improved culture-system based research. Addressing the lack of attention paid to culture environments is critical to improve the reproducibility and translation of preclinical research, but constitutes only an initial step towards enhancing the relevance of in vitro cell cultures towards in vivo physiology.

9.
Hum Exp Toxicol ; 41: 9603271211073708, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35112887

RESUMO

Current human immunodeficiency virus treatments need to be periodically administered lifelong. In this study we assess the effect of repeated doses of an anti-HIV peptide drug candidate in C57BL6 strain. Two schemes of up to 15 administrations and one of 30, daily dosing for 5 days per week, all by the subcutaneous route were evaluated. Different dose concentrations of the peptide were assayed. CIGB-210 treated animals showed no symptoms or abnormal behavior as compared with placebo. All the animals gained weight during the study. Macroscopic evaluation showed no alterations in any of the organs studied. Microscopic analysis of the tissues did not show morphological changes in thymus, stomach, small and large intestines, kidney, brain, or cerebellum. The proliferative response of splenocytes and their capacity to secrete gamma interferon were not compromised by the repeated administration of CIGB-210. There were not statistically significant differences for any of the parameters evaluated during the study among treated and non-treated groups. We can conclude that CIGB-210 is well tolerated in C57BL6 mice in the dose concentration range explored and merits subsequent toxicological studies.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Avaliação Pré-Clínica de Medicamentos , Drogas em Investigação/uso terapêutico , Infecções por HIV/tratamento farmacológico , Peptídeos/uso terapêutico , Animais , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL
10.
BMC Plant Biol ; 22(1): 63, 2022 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-35120456

RESUMO

BACKGROUND: The polyphyletic group of seagrasses shows an evolutionary history from early monocotyledonous land plants to the marine environment. Seagrasses form important coastal ecosystems worldwide and large amounts of seagrass detritus washed on beaches might also be valuable bioeconomical resources. Despite this importance and potential, little is known about adaptation of these angiosperms to the marine environment and their cell walls. RESULTS: We investigated polysaccharide composition of nine seagrass species from the Mediterranean, Red Sea and eastern Indian Ocean. Sequential extraction revealed a similar seagrass cell wall polysaccharide composition to terrestrial angiosperms: arabinogalactans, pectins and different hemicelluloses, especially xylans and/or xyloglucans. However, the pectic fractions were characterized by the monosaccharide apiose, suggesting unusual apiogalacturonans are a common feature of seagrass cell walls. Detailed analyses of four representative species identified differences between organs and species in their constituent monosaccharide composition and lignin content and structure. Rhizomes were richer in glucosyl units compared to leaves and roots. Enhalus had high apiosyl and arabinosyl abundance, while two Australian species of Amphibolis and Posidonia, were characterized by high amounts of xylosyl residues. Interestingly, the latter two species contained appreciable amounts of lignin, especially in roots and rhizomes whereas Zostera and Enhalus were lignin-free. Lignin structure in Amphibolis was characterized by a higher syringyl content compared to that of Posidonia. CONCLUSIONS: Our investigations give a first comprehensive overview on cell wall composition across seagrass families, which will help understanding adaptation to a marine environment in the evolutionary context and evaluating the potential of seagrass in biorefinery incentives.


Assuntos
Adaptação Biológica/genética , Alismatales/química , Parede Celular/química , Folhas de Planta/química , Raízes de Plantas/química , Polissacarídeos/química , Zosteraceae/química , Alismatales/genética , Parede Celular/genética , Oceano Índico , Biologia Marinha , Mar Mediterrâneo , Folhas de Planta/genética , Raízes de Plantas/genética , Polissacarídeos/genética , Especificidade da Espécie , Zosteraceae/genética
11.
Cir Cir ; 89(4): 469-475, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34352864

RESUMO

OBJETIVO: describir la experiencia inicial en Colombia en el manejo del melanoma de extremidad con perfusión aislada y comparar la respuesta de los subtipos histológicos más frecuentes en Colombia con la literatura. MATERIALES Y MÉTODOS: estudio descriptivo, retrospectivo de una serie de pacientes con diagnóstico de melanoma con metástasis en tránsito tratados con perfusión aislada de extremidad, seleccionados entre 2007 y 2016. Las variables cualitativas se analizaron con frecuencias absolutas y relativas. Las cuantitativas con medidas de tendencia central y dispersión. RESULTADOS: 11 pacientes fueron tratados con perfusión aislada de extremidad. Hubo respuesta parcial en siete pacientes (63,6%), enfermedad estable en dos pacientes (18,2%) y progresión en dos pacientes (18,2%). Después del tratamiento, cinco pacientes (45,5%) presentaron complicaciones menores. CONCLUSIONES: la perfusión aislada sigue siendo importante para el tratamiento del melanoma localmente avanzado con el fin de mejorar la calidad de vida de los pacientes. La respuesta puede cambiar según el tipo clínico de melanoma, siendo menor, según este estudio, en pacientes con melanoma lentiginoso acral y nodular, aunque por el bajo poder, esto no se puede concluir. OBJECTIVE: to describe the initial experience in Colombia of locally advanced melanoma treated by isolated limb perfusion and compare the response rate of our melanoma subtypes with the literature. METHODS: descriptive, retrospective study of a series of patients selected between 2007 and 2016. Qualitative variables were analyzed with proportions and frequencies, and quantitative variable with central tendency measures and measures of dispersion. RESULTS: 11 patients were treated by isolated limb perfusion. After the treatment, seven patients (63.6%) had partial response, two patients (18.2%) had stable disease and two patients (18.2%) had disease progression. Five patients (45.5%) had mild complications. CONCLUSIONS: Isolated limb perfusion is still an important treatment strategy for locally advanced melanoma, with the goal of improving the patient quality of life. The response can change according to the type of melanoma, and could be smaller in patients with acral lentiginous and nodular melanoma, although we cannot make this conclusion with this type of study because it has low power and lack of a comparison group.


Assuntos
Melanoma , Qualidade de Vida , Humanos , Melanoma/tratamento farmacológico , Estudos Retrospectivos
12.
Breast Cancer Res Treat ; 186(1): 15-24, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33611666

RESUMO

AIM: To provide a comprehensive overview of breast cancer in Colombia. METHODS: Data on breast cancer in Colombia are scarce. We present incidence data from population-based cancer registries that represent 4 distinct regions of the country. Other data originate from non-governmental institutions and healthcare providers within Colombia, official sources, expert opinion, Colombian legislation, and the Cancer Mortality Atlas publishes by Colombian National Cancer Institute. RESULTS: In Colombia, the age-standardized incidence rate remained relatively stable between 2012 and 2020 (43.1 to 47.8 cases per 100,000 women-years); Additionally, survival since 1995 has presented a substantial improvement from 65.7 to 72.1. In 33% of cases, the diagnosis of breast cancer was made in advanced stages, stage III or higher. The health demography survey conducted in 2015 showed that the participation in mammography screening in women aged 40 to 69 remains low 48.1%. Some limitations regarding access to early detection and diagnosis include economic strata, health insurance coverage, origin, and accessibility. On average, a 90-day period was reported from onset of symptoms to diagnosis of breast cancer. CONCLUSION: The first action towards improving outcomes in breast cancer should be to improve stage at diagnosis and timely access to care.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/terapia , Colômbia/epidemiologia , Atenção à Saúde , Detecção Precoce de Câncer , Feminino , Humanos , Mamografia
13.
ISME J ; 15(1): 141-153, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32934356

RESUMO

Coral reef research has predominantly focused on the effect of temperature on the breakdown of coral-dinoflagellate symbioses. However, less is known about how increasing temperature affects the establishment of new coral-dinoflagellate associations. Inter-partner specificity and environment-dependent colonization are two constraints proposed to limit the acquisition of more heat tolerant symbionts. Here, we investigated the symbiotic dynamics of various photosymbionts in different host genotypes under "optimal" and elevated temperature conditions. To do this, we inoculated symbiont-free polyps of the sea anemone Exaiptasia pallida originating from Hawaii (H2), North Carolina (CC7), and the Red Sea (RS) with the same mixture of native symbiont strains (Breviolum minutum, Symbiodinium linucheae, S. microadriaticum, and a Breviolum type from the Red Sea) at 25 and 32 °C, and assessed their ITS2 composition, colonization rates, and PSII photochemical efficiency (Fv/Fm). Symbiont communities across thermal conditions differed significantly for all hosts, suggesting that temperature rather than partner specificity had a stronger effect on symbiosis establishment. Overall, we detected higher abundances of more heat resistant Symbiodiniaceae types in the 32 °C treatments. Our data further showed that PSII photophysiology under elevated temperature improved with thermal pre-exposure (i.e., higher Fv/Fm), yet, this effect depended on host genotype and was influenced by active feeding as photochemical efficiency dropped in response to food deprivation. These findings highlight the role of temperature and partner fidelity in the establishment and performance of symbiosis and demonstrate the importance of heterotrophy for symbiotic cnidarians to endure and recover from stress.


Assuntos
Dinoflagellida , Anêmonas-do-Mar , Animais , Dinoflagellida/genética , Havaí , Temperatura Alta , Simbiose , Temperatura
14.
Front Public Health ; 8: 543322, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33304871

RESUMO

Uniform CO2 during human evolution (180 to 280 ppm) resulted, because of the role of the CO2-bicarbonate buffer in regulating pH, in rather constant pH (7.35 to 7.45) in human fluids, cells and tissues, determining, in turn, the narrow pH range for optimal functioning of the human proteome. Herein, we hypothesize that chronic exposure to elevated pCO2 with increasing atmospheric CO2 (>400 ppm), and extended time spent in confined, crowded indoor atmospheres (pCO2 up to 5,000 ppm) with urban lifestyles, may be an important, largely overlooked driver of change in human proteome performance. The reduced pH (downregulated from 0.1 to 0.4 units below the optimum pH) of extant humans chronically exposed to elevated CO2 is likely to lead to proteome malfunction. This malfunction is due to protein misfolding, aggregation, charge distribution, and altered interaction with other molecules (e.g., nucleic acids, metals, proteins, and drugs). Such alterations would have systemic effects that help explain the prevalence of syndromes (obesity, diabetes, respiratory diseases, osteoporosis, cancer, and neurological disorders) characteristic of the modern lifestyle. Chronic exposure to elevated CO2 poses risks to human health that are too serious to be ignored and require testing with fit-for-purpose equipment and protocols along with indoor carbon capture technologies to bring CO2 levels down to approach levels (180-280 ppm) under which the human proteome evolved.


Assuntos
Dióxido de Carbono , Proteoma , Atmosfera , Bicarbonatos , Carbono , Dióxido de Carbono/efeitos adversos , Humanos
15.
Rev. colomb. cancerol ; 24(4): 187-187, oct.-dic. 2020.
Artigo em Espanhol | LILACS | ID: biblio-1289191
16.
Artigo em Inglês | MEDLINE | ID: mdl-32850499

RESUMO

The spread of the novel coronavirus (SARS-CoV-2) has triggered a global emergency, that demands urgent solutions for detection and therapy to prevent escalating health, social, and economic impacts. The spike protein (S) of this virus enables binding to the human receptor ACE2, and hence presents a prime target for vaccines preventing viral entry into host cells. The S proteins from SARS and SARS-CoV-2 are similar, but structural differences in the receptor binding domain (RBD) preclude the use of SARS-specific neutralizing antibodies to inhibit SARS-CoV-2. Here we used comparative pangenomic analysis of all sequenced reference Betacoronaviruses, complemented with functional and structural analyses. This analysis reveals that, among all core gene clusters present in these viruses, the envelope protein E shows a variant cluster shared by SARS and SARS-CoV-2 with two completely-conserved key functional features, namely an ion-channel, and a PDZ-binding motif (PBM). These features play a key role in the activation of the inflammasome causing the acute respiratory distress syndrome, the leading cause of death in SARS and SARS-CoV-2 infections. Together with functional pangenomic analysis, mutation tracking, and previous evidence, on E protein as a determinant of pathogenicity in SARS, we suggest E protein as an alternative therapeutic target to be considered for further studies to reduce complications of SARS-CoV-2 infections in COVID-19.


Assuntos
Betacoronavirus/química , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/genética , COVID-19 , Proteínas do Envelope de Coronavírus , Infecções por Coronavirus/virologia , Genes Essenciais , Genes Virais , Genoma Viral , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/química , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Mutação , Fases de Leitura Aberta , Domínios PDZ , Pandemias , Pneumonia Viral/virologia , Domínios Proteicos , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/química , SARS-CoV-2 , Proteínas Viroporinas
17.
Mar Pollut Bull ; 152: 110920, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32479293

RESUMO

Microplastic particles (MPs) in the gastrointestinal tracts of nine fish species of commercial importance from different habitats (coastal, pelagic, and reef-associated) in the Saudi EEZ of the Arabian Gulf were quantified and classified. A total of eight MPs were retrieved from a total of 140 individual fish examined, with an average of 0.057 ± 0.019 microplastic items per fish (excluding possible plastic fibers). On average, 5.71%, of the fish dissected contained MPs, ranging from 5 to 15% of individual fish examined containing MPs among species (Siganus canaliculatus and Rastrelliger kanagurta, respectively). Ingested plastic consisted primarily of fishing threads (1.04 ± 0.06 mm), followed by fragments (1.16 ± 0.11 mm). It is likely that the fibers, originated from the fisheries, recreational boating, laundry, domestic wastewater, and other human activities, which is also widespread and abundant (found in 58.58% of the fish studied). Polyethylene (PE) and polypropylene (PP) were identified as the most abundant polymers ingested by the fishes. There was no significant difference (p < 0.05) between the presence of microplastic in fish depending on their habitat. The prevalence of MPs is relatively low compared to those in other regions, despite the massive industrialization of the Saudi Arabian Gulf.


Assuntos
Plásticos , Poluentes Químicos da Água/análise , Animais , Monitoramento Ambiental , Peixes , Microplásticos , Arábia Saudita
18.
Environ Pollut ; 255(Pt 2): 113281, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31600700

RESUMO

Only 1% of plastic entering the ocean is found floating on its surface, with high loads in ocean accumulation zones and semi-enclosed seas, except for the Red Sea, which supports one of the lowest floating plastic loads worldwide. Given the extension of reefs in the Red Sea, we hypothesize a major role of scleractinian corals as sinks, through suspension-feeding, and assessed microplastic removal rates by three Red Sea coral species. Experimental evidence showed removal rates ranging from 0.25 × 10-3 to 14.8 × 10-3 microplastic particles polyp-1 hour-1, among species. However, this was only 2.2 ±â€¯0.6% of the total removal rate, with passive removal through adhesion to the coral surface being 40 times higher than active removal through suspension-feeding. These results point at adhesion of plastic to coral reef structures as a major sink for microplastics suspended in the water column after sinking, helping explain low concentrations in Red Sea surface waters.


Assuntos
Antozoários , Monitoramento Ambiental , Microplásticos/análise , Poluentes Químicos da Água/análise , Animais , Recifes de Corais , Oceano Índico , Oceanos e Mares , Plásticos , Água do Mar
19.
Educ. med. super ; 33(1): e1763, ene.-mar. 2019. tab, fig
Artigo em Espanhol | LILACS, CUMED | ID: biblio-1089885

RESUMO

Introducción: El aprendizaje basado en problemas es una estrategia pedagógica basada en el estudiante como protagonista de su propio aprendizaje, la cual constituye una nueva perspectiva de la enseñanza. A nivel universitario es una estrategia que se perfila como uno de los enfoques más innovadores en la formación académica actual, cobrando cada vez más espacio en las universidades del mundo. Objetivo: Analizar la estrategia de aprendizaje basado en problemas en el desarrollo de las competencias transversales, instrumentales, sistémicas en estudiantes Universitarios de primer semestre de programas del área de la salud. Métodos: La muestra fue de 465 estudiantes. Todos ellos desarrollaron el tema de valores y medio ambiente en el curso de biología empleando aprendizaje basado en problemas, posterior a lo cual, mediante el cuestionario de evaluación de las competencias transversales se evaluó el desarrollo que lograron en cada una de las competencias. Resultados: Sugirieron un mayor desarrollo de las competencias sistémicas con la implementación de esta estrategia. Conclusiones: Ésta estrategia posiblemente favorece el trabajo colaborativo, en los estudiantes(AU)


Introduction: The Problem-based learning is a pedagogic strategy based on the student as the primary author of his own learning, this strategy constitutes a new perspective of teaching. At college level Problem-based learning is outlined like one of the most innovative approaches in the current academic education. Objective: The aim of this research was to analyze the strategy of Problem-based learning in the development of transversal, instrumental and systemic competencies in college first semester students, in the healthy area. Methods: The sample was composed by 465 students. All of them developed the topic about values and environment in the frame of biology course employing Problem-based learning. following that they completed an evaluation questionnaire about transversal competencies, which evaluated the development achieved in each of the competences. Results: The results suggest a greater development of the systemics competences with the use of the Problem-based learning strategy. Conclusions: We concluded that this strategy Problem-based learning possibly helps to favor the collaborative work in college students(AU)


Assuntos
Humanos , Organizações , Aprendizagem Baseada em Problemas , Universidades
20.
J Immunoassay Immunochem ; 40(2): 193-213, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30497338

RESUMO

The synthetic peptide CIGB-210 is a promising anti-HIV drug candidate shown to inhibit HIV replication in MT4 cells at the nanomolar range by triggering the rearrangement of vimentin intermediate filaments. Sensitive and specific analytical methods are required for pharmacological studies of CIBG-210 in animals. In this study, we describe the development of a competitive ELISA for the quantitative determination of CIGB-210 using an anti-CIGB-210 hyperimmune serum. After optimization of all the steps, the assay exhibited a dynamic range from 11.87 to 0.0095 µg/mL. The intra-assay coefficient of variation (CV) was lower than or close to 5% for all the six concentrations of the calibrator, and the inter-assay CV was below 10% in five out of the six concentrations tested. No interference of either murine or human plasma was observed. The analyte was stable in plasma after five freeze-thaw cycles, while the hyperimmune serum maintained its binding capacity after 10 freeze-thaw cycles. Furthermore, the ELISA was able to detect the two main metabolites of CIGB-210, although with a tenfold decrease in sensitivity. Our results demonstrate the utility and feasibility of this analytical method for pharmacological experiments in animals as humans.


Assuntos
Fármacos Anti-HIV/análise , Fármacos Anti-HIV/sangue , Líquidos Corporais/química , Ensaio de Imunoadsorção Enzimática , Animais , Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/química , Humanos , Camundongos , Peptídeos/análise , Peptídeos/sangue , Peptídeos/síntese química , Peptídeos/química
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