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1.
Gastroenterology ; 161(5): 1584-1600, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34245764

RESUMEN

BACKGROUND & AIMS: SIRT5 plays pleiotropic roles via post-translational modifications, serving as a tumor suppressor, or an oncogene, in different tumors. However, the role SIRT5 plays in the initiation and progression of pancreatic ductal adenocarcinoma (PDAC) remains unknown. METHODS: Published datasets and tissue arrays with SIRT5 staining were used to investigate the clinical relevance of SIRT5 in PDAC. Furthermore, to define the role of SIRT5 in the carcinogenesis of PDAC, we generated autochthonous mouse models with conditional Sirt5 knockout. Moreover, to examine the mechanistic role of SIRT5 in PDAC carcinogenesis, SIRT5 was knocked down in PDAC cell lines and organoids, followed by metabolomics and proteomics studies. A novel SIRT5 activator was used for therapeutic studies in organoids and patient-derived xenografts. RESULTS: SIRT5 expression negatively regulated tumor cell proliferation and correlated with a favorable prognosis in patients with PDAC. Genetic ablation of Sirt5 in PDAC mouse models promoted acinar-to-ductal metaplasia, precursor lesions, and pancreatic tumorigenesis, resulting in poor survival. Mechanistically, SIRT5 loss enhanced glutamine and glutathione metabolism via acetylation-mediated activation of GOT1. A selective SIRT5 activator, MC3138, phenocopied the effects of SIRT5 overexpression and exhibited antitumor effects on human PDAC cells. MC3138 also diminished nucleotide pools, sensitizing human PDAC cell lines, organoids, and patient-derived xenografts to gemcitabine. CONCLUSIONS: Collectively, we identify SIRT5 as a key tumor suppressor in PDAC, whose loss promotes tumorigenesis through increased noncanonic use of glutamine via GOT1, and that SIRT5 activation is a novel therapeutic strategy to target PDAC.


Asunto(s)
Carcinoma Ductal Pancreático/enzimología , Metabolismo Energético , Neoplasias Pancreáticas/enzimología , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Sirtuinas/deficiencia , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Aspartato Aminotransferasa Citoplasmática/genética , Aspartato Aminotransferasa Citoplasmática/metabolismo , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patología , Línea Celular Tumoral , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacología , Progresión de la Enfermedad , Metabolismo Energético/efectos de los fármacos , Activación Enzimática , Activadores de Enzimas/farmacología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Ratones Endogámicos C57BL , Ratones Endogámicos NOD , Ratones Noqueados , Ratones SCID , Mutación , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Proteínas Proto-Oncogénicas p21(ras)/genética , Transducción de Señal , Sirtuinas/genética , Carga Tumoral , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto , Gemcitabina
2.
Geriatr Nurs ; 42(1): 181-187, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32800603

RESUMEN

INTRODUCTION: Individuals living with dementia are likely to experience one or more neuropsychiatric symptoms on a daily basis. Dance has the potential to positively impact and reduce these symptoms. This integrative review was conducted to identify the impacts of dance on agitation and anxiety among those living with dementia. METHODS: An integrative review methodology guided the literature search and evaluation. Thirty-Nine papers were retrieved from the initial search. Five studies were included in the review. The Mixed Methods Appraisal Tool was used to assess the quality of relevant articles. RESULTS: Three quantitative and 2 qualitative studies were reviewed. Three out of 4 studies found dance positively impacted agitation. While 1 out of 2 studies reported improvements in anxiety. DISCUSSION: This review suggests that dance has the potential to impact anxiety and agitation symptoms of persons living with dementia. However, the evidence is weak and further research is warranted.


Asunto(s)
Baile , Demencia , Ansiedad , Demencia/psicología , Humanos , Agitación Psicomotora
3.
Curr Med Chem ; 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38659265

RESUMEN

INTRODUCTION: During pregnancy, the woman's body undergoes anatomical and physiological changes, making this period susceptible to maternal-fetal diseases and complications. The consequences of not treating pregnant women include premature birth, low birth weight fetuses, and postnatal behavior disorders. Developing new therapies can accelerate the discovery of safe and effective drugs, contributing to designing novel natural and synthetic products to treat complications the pregnancy. OBJECTIVE: This study aimed to carry out a patent review to identify and explore trends in innovation and therapeutic strategies for treating pregnant women. METHODS: The Espacenet and WIPO databases were used, with the inclusion criteria being the keywords "pregnancy and drug" and code A61k, from 2008 to 2023, and as exclusion were the access to the patent and focus on human pregnant women. RESULTS: After the final screening, 32 patents were selected, with strategies for the treatment of diseases in pregnant women. Of these, 20 patents are on preclinical studies on animals and 12 on pregnant women. It was observed that universities lead the ranking of applications (17/32), and China has the highest number of patents (18/32). Most findings contain herbal medicines and/or the association of natural extracts with synthetic drugs. CONCLUSION: From this perspective, new drug administration systems were also developed, which can be a promising source for obtaining new medicines for the treatment of pregnant women; however, research is still limited and shows a gap in stimulating the rapid development of safe drugs that improve the health of pregnant women.

4.
Brain Sci ; 14(2)2024 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-38391705

RESUMEN

Investigating new drugs or formulations that target Alzheimer disease (AD) is critical for advancing therapeutic interventions. Therefore, this study aimed to assess the effectiveness of nanoencapsulated curcumin (NC Curc) in alleviating memory impairment, oxidative stress, and neuroinflammation in a validated AD model. Male Wistar rats were given bilateral intracerebroventricular injections of either saline or streptozotocin (STZ) (3 mg/3 µL/site) to establish the AD model (day 0). On day 22, daily oral administrations of curcumin (6 mg/kg), NC Curc (6 mg/kg), or a vehicle (unloaded NC) were initiated and continued for 14 days. NC Curc significantly reversed memory deficits in object recognition and inhibitory avoidance tests induced by STZ. Both formulations of curcumin attenuated elevated acetylcholinesterase activity caused by STZ. Importantly, NC Curc alone effectively mitigated STZ-induced oxidative stress. Additionally, NC Curc treatment normalized GFAP levels, suggesting a potential reduction in neuroinflammation in STZ-treated rats. Our findings indicate that NC Curc improves memory in an AD rat model, highlighting its enhanced therapeutic effects compared to unencapsulated curcumin. This research significantly contributes to understanding the therapeutic and neurorestorative potential of NC Curc in AD, particularly in reversing pathophysiological changes.

5.
Cancer Discov ; 14(1): 176-193, 2024 01 12.
Artículo en Inglés | MEDLINE | ID: mdl-37931287

RESUMEN

Nutritional factors play crucial roles in immune responses. The tumor-caused nutritional deficiencies are known to affect antitumor immunity. Here, we demonstrate that pancreatic ductal adenocarcinoma (PDAC) cells can suppress NK-cell cytotoxicity by restricting the accessibility of vitamin B6 (VB6). PDAC cells actively consume VB6 to support one-carbon metabolism, and thus tumor cell growth, causing VB6 deprivation in the tumor microenvironment. In comparison, NK cells require VB6 for intracellular glycogen breakdown, which serves as a critical energy source for NK-cell activation. VB6 supplementation in combination with one-carbon metabolism blockage effectively diminishes tumor burden in vivo. Our results expand the understanding of the critical role of micronutrients in regulating cancer progression and antitumor immunity, and open new avenues for developing novel therapeutic strategies against PDAC. SIGNIFICANCE: The nutrient competition among the different tumor microenvironment components drives tumor growth, immune tolerance, and therapeutic resistance. PDAC cells demand a high amount of VB6, thus competitively causing NK-cell dysfunction. Supplying VB6 with blocking VB6-dependent one-carbon metabolism amplifies the NK-cell antitumor immunity and inhibits tumor growth in PDAC models. This article is featured in Selected Articles from This Issue, p. 5.


Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Vitamina B 6 , Microambiente Tumoral , Células Asesinas Naturales , Neoplasias Pancreáticas/patología , Carcinoma Ductal Pancreático/patología , Carbono
6.
Nat Cell Biol ; 26(4): 613-627, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38429478

RESUMEN

The ability of tumour cells to thrive in harsh microenvironments depends on the utilization of nutrients available in the milieu. Here we show that pancreatic cancer-associated fibroblasts (CAFs) regulate tumour cell metabolism through the secretion of acetate, which can be blocked by silencing ATP citrate lyase (ACLY) in CAFs. We further show that acetyl-CoA synthetase short-chain family member 2 (ACSS2) channels the exogenous acetate to regulate the dynamic cancer epigenome and transcriptome, thereby facilitating cancer cell survival in an acidic microenvironment. Comparative H3K27ac ChIP-seq and RNA-seq analyses revealed alterations in polyamine homeostasis through regulation of SAT1 gene expression and enrichment of the SP1-responsive signature. We identified acetate/ACSS2-mediated acetylation of SP1 at the lysine 19 residue that increased SP1 protein stability and transcriptional activity. Genetic or pharmacologic inhibition of the ACSS2-SP1-SAT1 axis diminished the tumour burden in mouse models. These results reveal that the metabolic flexibility imparted by the stroma-derived acetate enabled cancer cell survival under acidosis via the ACSS2-SP1-SAT1 axis.


Asunto(s)
Fibroblastos Asociados al Cáncer , Neoplasias Pancreáticas , Animales , Ratones , Fibroblastos Asociados al Cáncer/metabolismo , Línea Celular Tumoral , Acetatos/farmacología , Acetatos/metabolismo , Neoplasias Pancreáticas/genética , Poliaminas , Microambiente Tumoral
7.
IDCases ; 33: e01823, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37441582

RESUMEN

Erythema nodosum leprosum (ENL), characterized by erythematous subcutaneous nodules with multiorgan involvement and systemic manifestations such as neuritis, arthritis, and orchitis, affects approximately 50 % of patients with lepromatous leprosy (LL). It has also been associated with testicular atrophy and adult-onset hypogonadism, but testicular nodules have rarely been reported. We present the case of a 35-year-old male patient with biopsy confirmed LL who completed multidrug therapy and presented for follow-up with a complaint of testicular tenderness. His disease course had been complicated by ENL and polyneuritis. At the time, physical examination revealed a palpable tender nodule in the left testicle. Testicular ultrasound and magnetic resonance imaging showed bilateral intratesticular masses, of which the differential diagnosis included malignancy and inflammatory or postinfectious granulomatous process. Laboratory workup, testicular malignancy markers, and hormone levels were within normal limits. In view of the patient's underlying condition and after Urology evaluation, a diagnosis of granulomatous process was favored. The patient completed a prednisone taper followed by a 3-day prednisone pulse and weekly methotrexate, with sequential testicular ultrasounds to monitor response. After a year of close follow-up and slow tapering of methotrexate, the patient achieved complete resolution of the left intratesticular mass and decrease in size of the contralateral mass, evidenced by both physical examination and imaging. This case highlights the importance of a high index of suspicion in patients with LL and ENL who present with testicular nodules, as awareness of testicular involvement in this population is imperative to avoid life altering procedures such as orchiectomy.

8.
Asian Pac J Cancer Prev ; 23(10): 3491-3499, 2022 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-36308375

RESUMEN

BACKGROUND: Numerous pathogenic complications affect the skin and are preventable, such as skin cancer, microbial diseases, dermal irritations, and anaphylaxis. In this context, the correct use of skin products, including sunscreens and child makeup, is important for promoting skin health and preventing adverse health conditions. OBJECTIVE: This study aimed to use educational and playful activities to promote skin health for students. METHODS: This project was development in a municipal elementary school (Rio Grande do Sul State, Brazil). The interventions were divided into three moments. In the first day, a questionnaire was applied to find out the students' previous knowledge about photoprotection. On the second day, an intervention lecture was held addressing issues related to photoprotection and the use of makeup. Finally, we played educational and ludic games and after, the questionnaire was reapplied. This was done to evaluate these actions' effectiveness regarding photoprotection and record their habits by applying a structured questionnaire at the beginning and end of the activities. RESULTS: Students received positively and interacted significantly during all activities performed. Regarding the impact of this study, we observed that ten times more students considered using sunscreen as something important at the end of the project, as only 8.16% of participants knew what skin cancer was at the beginning of the experiment. After the educational activities, this number rose to 72.37%, and 92.86% of girls reported wearing makeup, with more than half being expired or unlabeled and only 21.6% being appropriate for child use. CONCLUSION: The measures demonstrated effectively improve students' level of information regarding skin cancer prevention and indicated that inappropriate habits concerning makeup use in childhood are quite common, demonstrating the importance of educational interventions for children, since can improve your health.


Asunto(s)
Conocimientos, Actitudes y Práctica en Salud , Neoplasias Cutáneas , Niño , Femenino , Humanos , Protectores Solares/uso terapéutico , Promoción de la Salud , Estudiantes , Neoplasias Cutáneas/etiología , Neoplasias Cutáneas/prevención & control , Neoplasias Cutáneas/tratamiento farmacológico , Encuestas y Cuestionarios
9.
Pharmacol Rep ; 74(1): 135-147, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34739705

RESUMEN

BACKGROUND: Surface functionalization enhances the properties and characteristics of polymeric nanocapsules (NCs) mainly due to the surface charge, surfactants, and polymer coating type. Curcumin (CUR) is a bioactive compound with several proven pharmacological properties and low bioavailability. This study aimed to develop anionic (poly-ɛ-caprolactone; PCL) and cationic (Eudragit® RS100 (EUD)) NCs prepared with sorbitan monostearate (Span 60®) or sorbitan monooleate (Span 80®), coated with d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and optimized using 23 factorial analysis. Subsequently, the biological activity was evaluated. METHODS: A two-level, three-factor design (polymer, Span type, and TPGS concentration) was used. The biological effects of CUR-loaded TPGS-coated cationic and anionic NCs were assessed in apomorphine-induced stereotyped behavior in rats. RESULTS: The type of polymer (anionic or cationic) and Span® had a factorial influence on the physical and chemical characteristics of NCs according to the changes in TPGS concentrations. Both cationic and anionic CUR-NCs could block apomorphine-induced behavioral changes. CONCLUSIONS: The CUR-loaded TPGS-coated NCs proved to be a promising brain delivery system.


Asunto(s)
Apomorfina/farmacología , Conducta Animal/efectos de los fármacos , Curcumina/farmacología , Nanocápsulas/química , Conducta Estereotipada/efectos de los fármacos , Animales , Agonistas de Dopamina/farmacología , Inhibidores Enzimáticos , Hexosas/farmacología , Plantas Medicinales , Ratas , Resultado del Tratamiento , Vitamina E/farmacología
10.
Oncogene ; 41(7): 971-982, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35001076

RESUMEN

Metabolic alterations regulate cancer aggressiveness and immune responses. Given the poor response of pancreatic ductal adenocarcinoma (PDAC) to conventional immunotherapies, we investigated the link between metabolic alterations and immunosuppression. Our metabolic enzyme screen indicated that elevated expression of CD73, an ecto-5'-nucleotidase that generates adenosine, correlates with increased aggressiveness. Correspondingly, we observed increased interstitial adenosine levels in tumors from spontaneous PDAC mouse models. Diminishing CD73 by genetic manipulations ablated in vivo tumor growth, and decreased myeloid-derived suppressor cells (MDSC) in orthotopic mouse models of PDAC. A high-throughput cytokine profiling demonstrated decreased GM-CSF in mice implanted with CD73 knockdowns. Furthermore, we noted increased IFN-γ expression by intratumoral CD4+ and CD8+ T cells in pancreatic tumors with CD73 knockdowns. Depletion of CD4+ T cells, but not CD8+ T cells abrogated the beneficial effects of decreased CD73. We also observed that splenic MDSCs from Nt5e knockdown tumor-bearing mice were incompetent in suppressing T cell activation in the ex vivo assays. Replenishing GM-CSF restored tumor growth in Nt5e knockout tumors, which was reverted by MDSC depletion. Finally, anti-CD73 antibody treatment significantly improved gemcitabine efficacy in orthotopic models. Thus, targeting the adenosine axis presents a novel therapeutic opportunity for improving the anti-tumoral immune response against PDAC.


Asunto(s)
Células Supresoras de Origen Mieloide
11.
Mater Sci Eng C Mater Biol Appl ; 118: 111356, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33254976

RESUMEN

The present study aimed to develop nanocapsules (NCs) loaded with curcumin (CCM) using different coatings, comparing the effect of these coatings on physicochemical properties of NCs. NCs were prepared by interfacial deposition of performed polymer, using different polymers as coatings (P80, PEG, Chitosan and Eudragit RS100®) and then, characterized in detail by different techniques (AFM, FTIR, DSC, XRD, among others). In vitro studies were performed, evaluating the release profile, cytotoxicity and antimalarial activity of CCM-loaded NCs. Overall, all CCM-loaded NCs samples exhibited typical characteristics as nanometric size, coating-dependent zeta potential, acidic pH value, span values below 2, homogeneous morphology and CCM-distribution in pseudophases of type VI (for all of coatings). Experimental results showed that CCM remains stable in lipid-core of NCs, maintaining its physicochemical and biological properties after nanoencapsulation process. In vitro release assays showed that nanoencapsulation was an efficient strategy to controlled release of CCM and P80-coated NCs presented slowest CCM-release considering all nanoformulations tested. Still, CCM-loaded NCs presented no cytotoxic effect. Also, all CCM-loaded NCs showed a perceptible antimalarial activity independently of their coatings (anionic and cationic), with more expressive results for CS-coated NCs. In conclusion, findings for CCM-loaded NCs and their different coatings seem to be a promising strategy to improve your biological activity.


Asunto(s)
Antimaláricos , Quitosano , Curcumina , Nanocápsulas , Antimaláricos/farmacología , Curcumina/farmacología , Polímeros
12.
Food Chem Toxicol ; 144: 111625, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32738367

RESUMEN

This study was designed to examine fetal and maternal toxicity of curcumin (CURC) loaded lipid-core nanocapsules (LNC) prepared with poly(ϵ-caprolactone) as a polymer, administered during the organogenesis period. Free CURC and CURC loaded-LNC (C-LNC) (2 mg/kg), blank LNC (B-LNC) and saline (CONTROL) were administered per oral route from the 7° to 13° gestational day (GD). Dams were evaluated daily for body weight gain, clinical signs, water and food intake. On 20° GD, dams were euthanized, organs were weighed and blood was collected for biochemical determinations. Fetal biometrics and external morphological anomalies were assessed. Also, were performed histopathological analysis of placenta and measurement of cytokines levels in placental and fetal liver tissues. All groups did not cause changes in dams during the pregnancy. Furthermore, treatments did not cause external morphological changes and delayed fetal development. Still, for histopathological analysis of placental tissue, treatments did not cause alterations in evaluated parameters. For cytokines levels, CURC and C-LNC caused a decrease in placental levels of TNF-α. Therefore, we have demonstrated that C-LNC did not cause toxicological effects (mother and fetus), in the same manner as pattern bioactive compound, proving to be a promising nutraceutical delivery system for maternal supplementation with CURC.


Asunto(s)
Curcumina/administración & dosificación , Desarrollo Fetal/efectos de los fármacos , Lípidos/química , Nanocápsulas , Placenta/efectos de los fármacos , Poliésteres/administración & dosificación , Animales , Peso Corporal/efectos de los fármacos , Citocinas/metabolismo , Conducta de Ingestión de Líquido/efectos de los fármacos , Conducta Alimentaria/efectos de los fármacos , Femenino , Masculino , Intercambio Materno-Fetal , Placenta/metabolismo , Embarazo , Ratas Wistar
13.
J Neuroimmunol ; 345: 577270, 2020 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-32480241

RESUMEN

The purpose of current study was to evaluate the effect of curcumin (CUR) loaded lipid-core nanocapsules (CUR-LNC) treatment on neuroinflammatory and behavioral alterations in a model of sickness behavior induced by lipopolysaccharide (LPS) in rats. Rats were treated with CUR-LNC and CUR daily for 14 days. After the last treatments, sickness behavior was induced with LPS. Sickness behavior LPS-induced was confirmed by behavioral tests, an increase in levels of proinflammatory cytokines, decrease in levels of IL-10, overexpression of IDO-1 and IDO-2. In conclusion, CUR-LNC treatment attenuated the neuroinflammatory and behavioral changes caused in sickness behavior model.


Asunto(s)
Curcumina/administración & dosificación , Conducta de Enfermedad/fisiología , Mediadores de Inflamación/inmunología , Lipopolisacáridos/toxicidad , Locomoción/fisiología , Nanocápsulas/administración & dosificación , Animales , Portadores de Fármacos/administración & dosificación , Conducta de Enfermedad/efectos de los fármacos , Mediadores de Inflamación/antagonistas & inhibidores , Mediadores de Inflamación/metabolismo , Lípidos , Locomoción/efectos de los fármacos , Masculino , Ratas , Ratas Wistar
14.
J Exp Med ; 217(7)2020 07 06.
Artículo en Inglés | MEDLINE | ID: mdl-32441762

RESUMEN

Approximately one third of cancer patients die due to complexities related to cachexia. However, the mechanisms of cachexia and the potential therapeutic interventions remain poorly studied. We observed a significant positive correlation between SIRT1 expression and muscle fiber cross-sectional area in pancreatic cancer patients. Rescuing Sirt1 expression by exogenous expression or pharmacological agents reverted cancer cell-induced myotube wasting in culture conditions and mouse models. RNA-seq and follow-up analyses showed cancer cell-mediated SIRT1 loss induced NF-κB signaling in cachectic muscles that enhanced the expression of FOXO transcription factors and NADPH oxidase 4 (Nox4), a key regulator of reactive oxygen species production. Additionally, we observed a negative correlation between NOX4 expression and skeletal muscle fiber cross-sectional area in pancreatic cancer patients. Knocking out Nox4 in skeletal muscles or pharmacological blockade of Nox4 activity abrogated tumor-induced cachexia in mice. Thus, we conclude that targeting the Sirt1-Nox4 axis in muscles is an effective therapeutic intervention for mitigating pancreatic cancer-induced cachexia.


Asunto(s)
Caquexia/complicaciones , Caquexia/metabolismo , NADPH Oxidasa 4/metabolismo , Neoplasias/complicaciones , Neoplasias/metabolismo , Transducción de Señal , Sirtuina 1/metabolismo , Tejido Adiposo/patología , Animales , Línea Celular , Línea Celular Tumoral , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Factores de Transcripción Forkhead/metabolismo , Células HEK293 , Humanos , Metaboloma/efectos de los fármacos , Ratones , Fibras Musculares Esqueléticas/efectos de los fármacos , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Atrofia Muscular/metabolismo , Atrofia Muscular/patología , FN-kappa B/metabolismo , Oxidación-Reducción , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Estabilidad Proteica/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Resveratrol/farmacología , Transducción de Señal/efectos de los fármacos , Síndrome Debilitante/patología
15.
World J Stem Cells ; 11(11): 1005-1019, 2019 Nov 26.
Artículo en Inglés | MEDLINE | ID: mdl-31768226

RESUMEN

BACKGROUND: Mesenchymal stem cells are pluripotent cells that have the ability to generate cells from a cell line or in other cell types from different tissues but from the same origin. Although those cells have more limited differentiation capacity than embryonic stem cells, they are easily obtained from somatic tissue and can be grown in large quantities. This characteristic of undifferentiated stem cells differentiating into different cell lines arouses strategies in regenerative medicine for the treatment of different diseases such as neurodegenerative diseases. AIM: To evaluate the cell differentiation capacity of human breastmilk stem cells for the three germ layers by a systematic review. METHODS: The searched databases were PubMed, EMBASE, OVID, and COCHRANE LIBRARY, published between 2007 and 2018 in the English language. All were in vitro studies for analysis of the "cell differentiation potential" in the literature using the keywords "human breastmilk," "stem cells," and keywords combined with the Boolean operator "NOT" were used to exclude those articles that had the word "CANCER" and their respective synonyms, which were previously consulted according to medical subject heading terms. PRISMA 2009 guidelines were followed in this study. RESULTS: A total of 315 titles and abstracts of articles were examined. From these, 21 were in common with more than one database, leaving 294 articles for analysis. Of that total, five publications met the inclusion criteria. When analyzing the publications, it was demonstrated that human breastmilk stem cells have a high cellular plasticity, exhibiting the ability to generate cells of all three germ layers, endoderm, mesoderm, and ectoderm, demonstrating their stemness. Those cells expressed the genes, TRA-1-60/81, octamer-binding transcription factor 4, and NANOG, of which NANOG, a critical regulator for self-renewal and maintenance, was the most highly expressed. Those cells have the ability to differentiate in vitro into adipocytes, chondrocytes, osteocytes, oligodendrocytes, astrocytes, and neurons as well hepatocytes, ß-pancreatic cells, and cardiomyocytes. CONCLUSION: Although the literature has been scarce, the pluripotentiality of these cells represents great potential for tissue engineering and cellular therapy. Further studies for safe clinical translation are needed.

17.
Reprod. clim ; 32(1): 7-14, 2017.
Artículo en Portugués | LILACS | ID: biblio-882430

RESUMEN

O diagnóstico genético pré-implantacional (PGD) é uma ferramenta que permite a selec¸ão do embrião saudável por meio da análise gênica e cromossômica. Beneficia casais no grupo de risco, como, por exemplo, casais com histórico de aborto de repetição ou com histórico familiar de doença hereditária. Diante do avanço das metodologias empregadas no PGD, esta revisão tem como objetivo reunir as informações acerca das técnicas de biópsia, de biologia molecular e aspectos bioéticos dessa prática. Assim, foi possível agregar as informações como vantagens, desvantagens, restrições e indicações referentes ao estágio embrionário em que é retirado o material genético e as técnicas de biologia molecular usadas na análise genética. Além disso, foi possível especificar alguns questionamentos bioéticos que surgem com a prática do PGD, como, por exemplo, a possível eugenia. Concluiu-se que a análise da trofoectoderme dos embriões e da aplicação da tecnologia de NGS é promissora para o futuro do PGD, bem como a primordialidade da criação de leis que regem e completam as lacunas no sentido ético e moral dessa prática.(AU)


The preimplantation genetic diagnosis (PGD) is a tool that allows the selection of healthy embrios through gene and chromosome analysis, benefiting couples at risk. Like couples with recurrent miscarriage or family history of hereditary disease. Given the advance of the methodologies used in PGD this review aims to assemble information about the biopsy techniques, molecular biology and bioethical aspects of this practice. Therefore, it was possible collect the information like advantages, disadvantages, restrictions and indications referring to embryonic stage in which is made the removal of genetic material and molecular biology techniques used in genetic analysis. In addition, some bioethic questions that arise with the practice of PGD were verified as, for example, possible Eugenia. It was concluded that the analysis of trofoectoderme of embryos and the application of NGS technology is promising for the future of PGD, as well as the primordiality the creating laws governing and complete the gaps in the ethical and moral sense of this practice.(AU)


Asunto(s)
Humanos , Femenino , Embarazo , Bioética , Pruebas Genéticas , Diagnóstico Preimplantación/estadística & datos numéricos , Técnicas Reproductivas Asistidas
18.
Eng. sanit. ambient ; 12(1): 79-89, jan.-mar. 2007. ilus, tab, graf
Artículo en Portugués | LILACS | ID: lil-455462

RESUMEN

O desempenho de unidades de contato que operam em regime de fluxo contínuo depende, entre outros, do padrão de escoamento que se desenvolve no seu interior. Já o levantamento de dados experimentais, como a elevação da superfície d'água e do campo de velocidades, não é uma tarefa fácil. Por tais razões, o uso de modelos numéricos na obtenção de padrões de escoamento em unidades de contato tem se tornado uma boa alternativa. A falta de dados hidrodinâmicos para a calibração e verificação de modelos numéricos tem sido um dos principais fatores que vem limitando o uso mais extensivo dessa ferramenta. O presente trabalho propõe uma nova técnica de calibração de modelo numérico, baseada no ajuste de curvas de passagem obtidas pelo modelo numérico e as obtidas experimentalmente ao longo das unidades de contato. A metodologia proposta é parcialmente avaliada e os resultados indicam ser essa uma técnica bastante promissora.


The performance of continuous flow contact units relies, among other factors, on the flow pattern inside them, and that the measurement of flow patterns in this type of unit is not an easy task. For this reason, the use of numerical models to obtain flow patterns in contact units has become a good alternative. However, the lack of hydrodynamic data to calibrate the models has been one of the main factors limiting a more extensive use of numerical models for this purpose. This work proposes a new calibration technique for numerical models which is based on the best fitting of measured and simulated flow through curves throughout the unit. The proposed methodology is partially evaluated and the results indicate it to be very promising.


Asunto(s)
Calibración , Flujo Continuo , Modelos Teóricos , Modelos Teóricos , Escorrentía
19.
Hig. aliment ; 21(154): 72-75, set. 2007. tab
Artículo en Portugués | LILACS | ID: lil-523199

RESUMEN

A baixa temperatura do gelado comestível não indica segurança microbiológica, mesmo porque com a proliferação das chamadas sorveterias artesanais, que nem sempre se apresentam em condições higiênicas satisfatórias, pode haver a contaminação desse produto pela utilização de leite cru, creme e ovos contaminados. Este trabalho teve como objetivo avaliar microbiologicamente os gelados comestíveis artesanais comercializados na cidade de Uberaba. As análises seguiram a metodologia segundo Silva; Junqueira; Silveira (1996). Das sete empresas avaliadas, 57,14 por cento (4/7) apresentam-se em condições higiênico-sanitárias inadequadas, oferecendo produtos com risco aos consumidores.


Asunto(s)
Contaminación de Alimentos , Manipulación de Alimentos , Higiene Alimentaria , Microbiología de Alimentos , Helados/microbiología , Brasil , Comercio , Helados Comestibles
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