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1.
Heliyon ; 10(9): e30125, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38726126

RESUMO

Introduction: Burnout syndrome (BS) is a prevalent occupational health problem in health professionals. To describe the prevalence and factors associated with BS in Peruvian health professionals. Method: A systematic review and meta-analysis were performed. The key terms "burnout" and "professional exhaustion" were used with words related to Peru. The databases consulted were LILACS/Virtual Health Library, Medline/PubMed, Science Direct, EBSCO, Scopus, SciELO, and RENATI-SUNEDU; articles published between January 2000 to December 2020 were considered for inclusion. Methodological quality was evaluated using the Newcastle-Ottawa scale. Results: Thirty studies were identified (8 scientific articles and 22 graduate theses). The median sample size was 78, with an interquartile range of 50-110. A meta-analysis was performed to calculate a dichotomic prevalence of burnout syndrome in health professionals of 25 % (95%CI: 9 %-45 %; I2 = 97.14 %; 5 studies). Also, our meta-analysis estimated the overall prevalence of mild burnout (27 %; 95%CI: 16%-41 %; I2 = 96.50 %), moderate burnout (48 %; 95%CI: 32%-65 %; I2 = 97.54 %), and severe burnout (17 %; 95%CI: 10%-24 %; I2 = 92.13 %; 18 studies). We present meta-analyses by region, profession, hospital area, and by dimension of the Maslach Burnout Inventory. Overall, the studies presented adequate levels of quality in 96.7 % of the included studies (n = 29). In addition, our narrative review of factors associated with BS and its three dimensions identified that different studies find associations with labor, socio-demographic, individual, and out-of-work factors. Conclusions: There is a higher prevalence of moderate BS in Peruvian health professionals at MINSA and EsSalud hospitals in Peru, with severity differing by region of Peru, type of profession, work area, and dimensions of BS.

2.
Mol Cancer ; 23(1): 83, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38730475

RESUMO

BACKGROUND: Active targeting by surface-modified nanoplatforms enables a more precise and elevated accumulation of nanoparticles within the tumor, thereby enhancing drug delivery and efficacy for a successful cancer treatment. However, surface functionalization involves complex procedures that increase costs and timelines, presenting challenges for clinical implementation. Biomimetic nanoparticles (BNPs) have emerged as unique drug delivery platforms that overcome the limitations of actively targeted nanoparticles. Nevertheless, BNPs coated with unmodified cells show reduced functionalities such as specific tumor targeting, decreasing the therapeutic efficacy. Those challenges can be overcome by engineering non-patient-derived cells for BNP coating, but these are complex and cost-effective approaches that hinder their wider clinical application. Here we present an immune-driven strategy to improve nanotherapeutic delivery to tumors. Our unique perspective harnesses T-cell exhaustion and tumor immune evasion to develop a groundbreaking new class of BNPs crafted from exhausted T-cells (NExT) of triple-negative breast cancer (TNBC) patients by specific culture methods without sophisticated engineering. METHODS: NExT were generated by coating PLGA (poly(lactic-co-glycolic acid)) nanoparticles with TNBC-derived T-cells exhausted in vitro by acute activation. Physicochemical characterization of NExT was made by dynamic light scattering, electrophoretic light scattering and transmission electron microscopy, and preservation and orientation of immune checkpoint receptors by flow cytometry. The efficacy of chemotherapy-loaded NExT was assessed in TNBC cell lines in vitro. In vivo toxicity was made in CD1 mice. Biodistribution and therapeutic activity of NExT were determined in cell-line- and autologous patient-derived xenografts in immunodeficient mice. RESULTS: We report a cost-effective approach with a good performance that provides NExT naturally endowed with immune checkpoint receptors (PD1, LAG3, TIM3), augmenting specific tumor targeting by engaging cognate ligands, enhancing the therapeutic efficacy of chemotherapy, and disrupting the PD1/PDL1 axis in an immunotherapy-like way. Autologous patient-derived NExT revealed exceptional intratumor accumulation, heightened chemotherapeutic index and efficiency, and targeted the tumor stroma in a PDL1+ patient-derived xenograft model of triple-negative breast cancer. CONCLUSIONS: These advantages underline the potential of autologous patient-derived NExT to revolutionize tailored adoptive cancer nanotherapy and chemoimmunotherapy, which endorses their widespread clinical application of autologous patient-derived NExT.


Assuntos
Nanopartículas , Linfócitos T , Humanos , Animais , Camundongos , Nanopartículas/química , Feminino , Linfócitos T/imunologia , Linfócitos T/metabolismo , Linhagem Celular Tumoral , Evasão da Resposta Imune , Neoplasias de Mama Triplo Negativas/terapia , Neoplasias de Mama Triplo Negativas/imunologia , Neoplasias de Mama Triplo Negativas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Diagnostics (Basel) ; 14(4)2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38396468

RESUMO

BACKGROUND: Corpus callosal abnormalities (CCA) are midline developmental brain malformations and are usually associated with a wide spectrum of other neurological and non-neurological abnormalities. The study aims to highlight the diagnostic role of fetal MRI to characterize heterogeneous corpus callosal abnormalities using the latest classification system. It also helps to identify associated anomalies, which have prognostic implications for the postnatal outcome. METHODS: In this study, retrospective data from antenatal women who underwent fetal MRI between January 2014 and July 2023 at Rush University Medical Center were evaluated for CCA and classified based on structural morphology. Patients were further assessed for associated neurological and non-neurological anomalies. RESULTS: The most frequent class of CCA was complete agenesis (79.1%), followed by hypoplasia (12.5%), dysplasia (4.2%), and hypoplasia with dysplasia (4.2%). Among them, 17% had isolated CCA, while the majority (83%) had complex forms of CCA associated with other CNS and non-CNS anomalies. Out of the complex CCA cases, 58% were associated with other CNS anomalies, while 8% were associated with non-CNS anomalies. 17% of cases had both. CONCLUSION: The use of fetal MRI is valuable in the classification of abnormalities of the corpus callosum after the confirmation of a suspected diagnosis on prenatal ultrasound. This technique is an invaluable method for distinguishing between isolated and complex forms of CCA, especially in cases of apparent isolated CCA. The use of diffusion-weighted imaging or diffusion tensor imaging in fetal neuroimaging is expected to provide further insights into white matter abnormalities in fetuses diagnosed with CCA in the future.

4.
Cancers (Basel) ; 16(2)2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38254826

RESUMO

Eosinophils in peripheral blood account for 0.3-5% of leukocytes, which is equivalent to 0.05-0.5 × 109/L. A count above 0.5 × 109/L is considered to indicate eosinophilia, while a count equal to or above 1.5 × 109/L is defined as hypereosinophilia. In bone marrow aspirate, eosinophilia is considered when eosinophils make up more than 6% of the total nuclear cells. In daily clinical practice, the most common causes of reactive eosinophilia are non-hematologic, whether they are non-neoplastic (allergic diseases, drugs, infections, or immunological diseases) or neoplastic (solid tumors). Eosinophilia that is associated with a hematological malignancy may be reactive or secondary to the production of eosinophilopoietic cytokines, and this is mainly seen in lymphoid neoplasms (Hodgkin lymphoma, mature T-cell neoplasms, lymphocytic variant of hypereosinophilic syndrome, and B-acute lymphoblastic leukemia/lymphoma). Eosinophilia that is associated with a hematological malignancy may also be neoplastic or primary, derived from the malignant clone, usually in myeloid neoplasms or with its origin in stem cells (myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions, acute myeloid leukemia with core binding factor translocations, mastocytosis, myeloproliferative neoplasms, myelodysplastic/myeloproliferative neoplasms, and myelodysplastic neoplasms). There are no concrete data in standardized cytological and cytometric procedures that could predict whether eosinophilia is reactive or clonal. The verification is usually indirect, based on the categorization of the accompanying hematologic malignancy. This review focuses on the broad differential diagnosis of hematological malignancies with eosinophilia.

5.
Anal Chem ; 95(42): 15450-15460, 2023 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-37814884

RESUMO

In this Perspective, we discuss the current status and advances in spatial transcriptomics technologies, which allow high-resolution mapping of gene expression in intact cell and tissue samples. Spatial transcriptomics enables the creation of high-resolution maps of gene expression patterns within their native spatial context, adding an extra layer of information to the bulk sequencing data. Spatial transcriptomics has expanded significantly in recent years and is making a notable impact on a range of fields, including tissue architecture, developmental biology, cancer, and neurodegenerative and infectious diseases. The latest advancements in spatial transcriptomics have resulted in the development of highly multiplexed methods, transcriptomic-wide analysis, and single-cell resolution utilizing diverse technological approaches. In this Perspective, we provide a detailed analysis of the molecular foundations behind the main spatial transcriptomics technologies, including methods based on microdissection, in situ sequencing, single-molecule FISH, spatial capturing, selection of regions of interest, and single-cell or nuclei dissociation. We contextualize the detection and capturing efficiency, strengths, limitations, tissue compatibility, and applications of these techniques as well as provide information on data analysis. In addition, this Perspective discusses future directions and potential applications of spatial transcriptomics, highlighting the importance of the continued development to promote widespread adoption of these techniques within the research community.


Assuntos
Perfilação da Expressão Gênica , Transcriptoma , Análise Serial de Tecidos , Núcleo Celular , Análise de Dados , Análise de Célula Única
6.
MicroPubl Biol ; 20232023.
Artigo em Inglês | MEDLINE | ID: mdl-37680216

RESUMO

Mutant B.4.1 , generated via EMS mutagenesis in Drosophila melanogaster , was studied by undergraduate students participating in the Fly-CURE. After inducing genetically mosaic tissue in the adult eye, B.4.1 mutant tissue displays a robust increase in cell division and a rough appearance. Complementation mapping and sequence analysis identified a nonsense mutation in the gene CG1603 , which we named clifford ( cliff ) due to observed increases in red-pigmented mutant tissue compared to controls. cliff encodes a zinc finger-containing protein implicated in transcriptional control. RNAi knockdown of cliff similarly results in rough eyes, confirming a role for Cliff in eye development.

7.
Cureus ; 15(8): e43082, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37680395

RESUMO

Catatonia is a behavioral syndrome characterized by a variety of symptoms such as mutism, stupor, rigidity, negativism, and verbigeration. It can be caused by various psychiatric and general medical conditions. While the diagnosis in the pediatric population is relatively uncommon, emerging literature supports a higher prevalence of catatonia in children. We present a 12-year-old girl with a complex medical and psychosocial history, including a functional neurological disorder and concerns for child abuse and Munchausen syndrome by proxy imposed by her mother. The patient was initially admitted for medical management of vomiting and refusal to eat. Child psychiatry was consulted for further assessment and noted multiple catatonic symptoms with a Busch-Francis catatonia rating scale (BFCRS) score of 22. A subsequent 1 mg IV lorazepam challenge test showed improvement in the patient's symptoms with a repeat BFCRS score of 10. This case supports emerging literature suggesting a higher prevalence of catatonia in children and the importance of recognizing this syndrome and its wide array of underlying causes.

8.
Eur J Med Chem ; 258: 115570, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37413883

RESUMO

Hyaluronic acid (HA) plays a crucial role in tumor growth and invasion through its interaction with cluster of differentiation 44 (CD44), a non-kinase transmembrane glycoprotein, among other hyaladherins. CD44 expression is elevated in many solid tumors, and its interaction with HA is associated with cancer and angiogenesis. Despite efforts to inhibit HA-CD44 interaction, there has been limited progress in the development of small molecule inhibitors. As a contribution to this endeavour, we designed and synthesized a series of N-aryltetrahydroisoquinoline derivatives based on existing crystallographic data available for CD44 and HA. Hit 2e was identified within these structures for its antiproliferative effect against two CD44+ cancer cell lines, and two new analogs (5 and 6) were then synthesized and evaluated as CD44-HA inhibitors by applying computational and cell-based CD44 binding studies. Compound 2-(3,4,5-trimethoxybenzyl)-1,2,3,4-tetrahydroisoquinolin-5-ol (5) has an EC50 value of 0.59 µM against MDA-MB-231 cells and is effective to disrupt the integrity of cancer spheroids and reduce the viability of MDA-MB-231 cells in a dose-dependent manner. These results suggest lead 5 as a promising candidate for further investigation in cancer treatment.


Assuntos
Ácido Hialurônico , Ácido Hialurônico/farmacologia , Ácido Hialurônico/química
10.
Acta méd. peru ; 40(3)jul. 2023.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1527619

RESUMO

Evaluar la validez y confiabilidad de un instrumento que mide la satisfacción de servicios nutricionales en pacientes renales. Material y Métodos: El estudio tuvo 7 fases dentro de las cuales se elaboró un instrumento que mide la satisfacción de pacientes de la Unidad de Salud renal, atendidos en talleres de nutrición por telemedicina, el cual se aplicó a 31 pacientes. Resultados: La validez de contenido global tuvo un índice de Lawshe igual a 0.95. La validez de constructo del cuestionario de satisfacción mediante análisis factorial exploratorio encontró 2 factores que corresponden al 87.5 % de variabilidad total. La confiabilidad del cuestionario tuvo un Alpha de Cronbach de 0.9. Conclusiones: El cuestionario que mide satisfacción de los pacientes renales atendidos por telemedicina tuvo alta validez de contenido, constructo y confiabilidad.


To evaluate the validity and reliability of an instrument that measures the satisfaction of nutritional services in renal patients. The study had 7 phases within which an instrument was developed that measures the satisfaction of the patients of the Renal Health Unit, attended in nutrition workshops by telemedicine, which was applied to 31 patients. The global content validity had a Lawshe index equal to 0.95. The construct validity of the satisfaction questionnaire through exploratory factor analysis found 2 factors that correspond to 87.5% of the total. The reliability of the questionnaire had a Cronbach's Alpha of 0.9. The questionnaire that measures the satisfaction of renal patients attended by telemedicine had high content, construct, and reliability validity.

11.
Neuropathol Appl Neurobiol ; 49(4): e12915, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37296499

RESUMO

AIMS: Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disorder caused by hypomorphic mutations of NBS1. NBS1 is a member of the MRE11-RAD50-NBS1 (MRN) complex that binds to DNA double-strand breaks and activates the DNA damage response (DDR). Nbs1 inactivation in neural progenitor cells leads to microcephaly and premature death. Interestingly, p53 homozygous deletion rescues the NBS1-deficient phenotype allowing long-term survival. The objective of this work was to determine whether simultaneous inactivation of Nbs1 and p53 in neural progenitors triggered brain tumorigenesis and if so in which category this tumour could be classified. METHODS: We generated a mouse model with simultaneous genetic inactivation of Nbs1 and p53 in embryonic neural stem cells and analysed the arising tumours with in-depth molecular analyses including immunohistochemistry, array comparative genomic hybridisation (aCGH), whole exome-sequencing and RNA-sequencing. RESULTS: NBS1/P53-deficient mice develop high-grade gliomas (HGG) arising in the olfactory bulbs and in the cortex along the rostral migratory stream. In-depth molecular analyses using immunohistochemistry, aCGH, whole exome-sequencing and RNA-sequencing revealed striking similarities to paediatric human HGG with shared features with radiation-induced gliomas (RIGs). CONCLUSIONS: Our findings show that concomitant inactivation of Nbs1 and p53 in mice promotes HGG with RIG features. This model could be useful for preclinical studies to improve the prognosis of these deadly tumours, but it also highlights the singularity of NBS1 among the other DNA damage response proteins in the aetiology of brain tumours.


Assuntos
Glioma , Proteína Supressora de Tumor p53 , Animais , Criança , Humanos , Camundongos , Proteínas de Ciclo Celular/genética , Glioma/genética , Homozigoto , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Deleção de Sequência , Proteína Supressora de Tumor p53/genética
12.
Cancer Res Commun ; 3(4): 709-724, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37377750

RESUMO

Most cancer-related deaths are due to metastases. Systemic factors, such as lipid-enriched environments [as low-density lipoprotein (LDL)-cholesterol], favor breast cancer, including triple-negative breast cancer (TNBC) metastasis formation. Mitochondria metabolism impacts TNBC invasive behavior but its involvement in a lipid-enriched setting is undisclosed. Here we show that LDL increases lipid droplets, induces CD36 and augments TNBC cells migration and invasion in vivo and in vitro. LDL induces higher mitochondrial mass and network spread in migrating cells, in an actin remodeling-dependent manner, and transcriptomic and energetic analyses revealed that LDL renders TNBC cells dependent on fatty acids (FA) usage for mitochondrial respiration. Indeed, engagement on FA transport into the mitochondria is required for LDL-induced migration and mitochondrial remodeling. Mechanistically, LDL treatment leads to mitochondrial long-chain fatty acid accumulation and increased reactive oxygen species (ROS) production. Importantly, CD36 or ROS blockade abolished LDL-induced cell migration and mitochondria metabolic adaptations. Our data suggest that LDL induces TNBC cells migration by reprogramming mitochondrial metabolism, revealing a new vulnerability in metastatic breast cancer. Significance: LDL induces breast cancer cell migration that relies on CD36 for mitochondrial metabolism and network remodeling, providing an antimetastatic metabolic strategy.


Assuntos
Lipoproteínas LDL , Neoplasias de Mama Triplo Negativas , Humanos , Lipoproteínas LDL/farmacologia , Neoplasias de Mama Triplo Negativas/metabolismo , Espécies Reativas de Oxigênio , Ácidos Graxos/farmacologia , Movimento Celular
13.
Crit Rev Food Sci Nutr ; : 1-29, 2023 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-37178132

RESUMO

Tree nuts and oily fruits are used as a diet complement and are highly consumed worldwide. The production and consumption of these foods have been increasing, and an enormous global market value is forecasted for 2023. Besides their high nutritional value and lipid content, they provide health benefits to fat metabolism, heart, skin, and brain. The industrial by-products of these oily foods represent promising raw materials for many industries. However, the lipidomic analysis of nuts and oily fruits is still in its early stages. State-of-the-art analytical approaches for the lipid profiling and fingerprinting of nuts and oily fruits have been developed using high-performance liquid chromatography and high-resolution mass spectrometry for the accurate identification and structural characterization at the molecular species level. It is expected to bring a new understanding of these everyday foods' nutritional and functional value. This review comprises the oil content and lipid composition of various nuts and oily fruits, particularly those mostly consumed worldwide and having recognized beneficial health effects, biological activities associated with the lipids from different oily foodstuffs, analytical methodologies to analyze lipids in nuts and oily fruits, and the potential biotechnological applications of their industrial by-products for a lipid-based commercial valorization.

15.
Biosens Bioelectron ; 219: 114770, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36270082

RESUMO

The detection of repetitive sequences with single-base resolution is becoming increasingly important aiming to understand the biological implications of genomic variation in these sequences. However, there is a lack of techniques to experimentally validate sequencing data from repetitive sequences obtained by Next-Generation Sequencing methods, especially in the case of Single-Nucleotide Variations (SNVs). That is one of the reasons why repetitive sequences have been poorly studied and excluded from most genomic studies. Therefore, in addition to sequencing data, there is an urgent need for efficient validation methods of genomic variation in these sequences. Herein we report the development of chemFISH, an alternative method for the detection of SNVs in repetitive sequences. ChemFISH is an innovative method based on dynamic chemistry labelling and abasic Peptide Nucleic Acid (PNA) probes to detect in situ the α-satellite DNA, organized in tandem repeats, with single-base resolution in a direct and rapid reaction. With this approach, we detected by microscopy the α-satellite DNA in a variety of human cell lines, we quantified the detection showing a low coefficient of variation among samples (13.16%-25.33%) and we detected single-base specificity with high sensitivity (82.41%-88.82%). These results indicate that chemFISH can serve as a rapid method to validate previously detected SNVs in sequencing data, as well as to find novel SNVs in repetitive sequences. Furthermore, the versatile chemistry behind chemFISH can lead to develop novel molecular assays for the in situ detection of nucleic acids.

17.
Arq. bras. oftalmol ; 86(6): e2021, 2023. graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1520196

RESUMO

ABSTRACT Purpose: The purpose of this study was to compare the white-to-white distance measurements of two devices (IOL Master 500 and Atlas corneal topographer) commonly used in clinical practice to determine if they were interchangeable. Providing information on instrument interchangeability could eliminate several unnecessary tests and consequently reduce the economic burden for the patient and society. Methods: In this prospective, comparative case series, the white-to-white distance was measured by independent examiners using the Atlas topographer (Carl Zeiss Meditec) and the IOL Master 500 (Carl Zeiss Meditec). One eye each of 184 patients was tested. Statistical analyses were performed using a paired t-test, Pearson correlation analysis, and Bland-Altman analysis to compare the measurement methods. Results: The mean white-to-white distance measurements with the Atlas topographer and the IOL Master 500 were 12.20 ± 0.44 mm and 12.12 ± 0.41 mm, respectively (p<0.001). The mean white-to-white difference between the two devices was 0.07 mm (95% confidence interval of mean difference: 0.04-0.11 mm). The Pearson correlation coefficient between the two devices was 0.85 (p<0.0001). The 95% limits of agreement between the two devices were -0.38 mm to 0.53 mm. Conclusions: The Atlas topographer and IOL Master 500 can be used interchangeably with respect to white-to-white distance measurements, as the range of differences is unlikely to affect clinical practice and decision making.


RESUMO Objetivo: O objetivo deste estudo é comparar as medições de diâmetro corneano de dois dispositivos normalmente utilizados na prática clínica (IOL Master 500 e Atlas topógrafo corneal) para ver se são permutáveis. O fornecimento de informações sobre a permutabilidade de instrumentos poderia eliminar vários testes desnecessários e, consequentemente, reduzir a carga econômica para o paciente e para a sociedade. Métodos: Nesta série de casos prospectivos e comparativos, a distância do diâmetro corneano foi medida por examinadores independentes utilizando o Topógrafo Atlas (Carl Zeiss Meditec) e o IOL Master 500 (Carl Zeiss Meditec), em um olho de 184 pacientes. A análise estatística foi realizada utilizando o teste t pareado, a correlação Pearson e a análise Bland-Altman para comparar os métodos de medição. Resultados: As medições médias da distância do diâmetro corneano com o topógrafo Atlas e o IOL Master 500 foram de 12,20 ± 0,44 mm e 12,12 ± 0,41 mm, respectivamente (p<0,001). A diferença média de WTW entre os dois dispositivos foi de 0,07 mm (intervalo de confiança de 95% da diferença média: 0,04 - 0,11 mm). O coeficiente de correlação Pearson entre os dois dispositivos foi de 0,85, p<0,0001. Os limites de concordância de 95% entre os dois dispositivos foram de -0,38 mm a 0,53 mm. Conclusões: O Atlas topographer e o IOL Master 500 podem ser utilizados permutavelmente em relação à medição do diâmetro corneano, uma vez que a gama de diferenças encontradas é pouco susceptível de afetar a prática clínica e a tomada de decisões.

18.
Mol Cell ; 82(23): 4537-4547.e7, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36327975

RESUMO

Inhibition of the electron transport chain (ETC) prevents the regeneration of mitochondrial NAD+, resulting in cessation of the oxidative tricarboxylic acid (TCA) cycle and a consequent dependence upon reductive carboxylation for aspartate synthesis. NAD+ regeneration alone in the cytosol can rescue the viability of ETC-deficient cells. Yet, how this occurs and whether transfer of oxidative equivalents to the mitochondrion is required remain unknown. Here, we show that inhibition of the ETC drives reversal of the mitochondrial aspartate transaminase (GOT2) as well as malate and succinate dehydrogenases (MDH2 and SDH) to transfer oxidative NAD+ equivalents into the mitochondrion. This supports the NAD+-dependent activity of the mitochondrial glutamate dehydrogenase (GDH) and thereby enables anaplerosis-the entry of glutamine-derived carbon into the TCA cycle and connected biosynthetic pathways. Thus, under impaired ETC function, the cytosolic redox state is communicated into the mitochondrion and acts as a rheostat to support GDH activity and cell viability.


Assuntos
Malato Desidrogenase , NAD , NAD/metabolismo , Malato Desidrogenase/genética , Malato Desidrogenase/metabolismo , Oxirredução , Ciclo do Ácido Cítrico/fisiologia , Respiração
19.
Int J Mol Sci ; 23(21)2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36361811

RESUMO

Modulation of lipid metabolism is a well-established cancer hallmark, and SCD1 has been recognized as a key enzyme in promoting cancer cell growth, including in glioblastoma (GBM), the deadliest brain tumor and a paradigm of cancer resistance. The central goal of this work was to identify, by MS, the phospholipidome alterations resulting from the silencing of SCD1 in human GBM cells, in order to implement an innovative therapy to fight GBM cell resistance. With this purpose, RNAi technology was employed, and low serum-containing medium was used to mimic nutrient deficiency conditions, at which SCD1 is overexpressed. Besides the expected increase in the saturated to unsaturated fatty acid ratio in SCD1 silenced-GBM cells, a striking increase in polyunsaturated chains, particularly in phosphatidylethanolamine and cardiolipin species, was noticed and tentatively correlated with an increase in autophagy (evidenced by the increase in LC3BII/I ratio). The contribution of autophagy to mitigate the impact of SCD1 silencing on GBM cell viability and growth, whose modest inhibition could be correlated with the maintenance of energetically associated mitochondria, was evidenced by using autophagy inhibitors. In conclusion, SCD1 silencing could constitute an important tool to halt GBM resistance to the available treatments, especially when coupled with a mitochondria disrupter chemotherapeutic.


Assuntos
Glioblastoma , Estearoil-CoA Dessaturase , Humanos , Estearoil-CoA Dessaturase/metabolismo , Fosfolipídeos , Glioblastoma/genética , Autofagia/genética , Sobrevivência Celular/genética
20.
Arq Bras Oftalmol ; 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35857985

RESUMO

PURPOSE: The purpose of this study was to compare the white-to-white distance measurements of two devices (IOL Master 500 and Atlas corneal topographer) commonly used in clinical practice to determine if they were interchangeable. Providing information on instrument interchangeability could eliminate several unnecessary tests and consequently reduce the economic burden for the patient and society. METHODS: In this prospective, comparative case series, the white-to-white distance was measured by independent examiners using the Atlas topographer (Carl Zeiss Meditec) and the IOL Master 500 (Carl Zeiss Meditec). One eye each of 184 patients was tested. Statistical analyses were performed using a paired t-test, Pearson correlation analysis, and Bland-Altman analysis to compare the measurement methods. RESULTS: The mean white-to-white distance measurements with the Atlas topographer and the IOL Master 500 were 12.20 ± 0.44 mm and 12.12 ± 0.41 mm, respectively (p<0.001). The mean white-to-white difference between the two devices was 0.07 mm (95% confidence interval of mean difference: 0.04-0.11 mm). The Pearson correlation coefficient between the two devices was 0.85 (p<0.0001). The 95% limits of agreement between the two devices were -0.38 mm to 0.53 mm. CONCLUSIONS: The Atlas topographer and IOL Master 500 can be used interchangeably with respect to white-to-white distance measurements, as the range of differences is unlikely to affect clinical practice and decision making.

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