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1.
Appl Physiol Nutr Metab ; 49(6): 838-843, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38700079

RESUMO

Hospital malnutrition remains a significant public health issue, particularly in developing countries. The Global Leadership Initiative on Malnutrition (GLIM) proposed homogenizing criteria to standardize malnutrition diagnosis. This study aimed to retrospectively determine the prevalence of nutritional risk and malnutrition diagnoses among hospitalized patients using the Nutritional Risk Screening (NRS)-2002 screening instrument and the GLIM criteria, respectively. We conducted a retrospective, cross-sectional study from nutritional records of patients hospitalized in a single centre 2021. Nutrition data from records included medical diagnosis, gender, length of stay, age, weight, height, body mass index, weight loss, calf circumference, and middle upper arm circumference. Nutritional risk and malnutrition were evaluated using NRS-2002 and GLIM criteria. Its concordance was further evaluated by using a Kappa test. The study included 616 records of patients; 52.3% (n = 322) of the population were male. The prevalence of nutritional risk, according to NRS-2002, was 69.5% (n = 428). Nutritional risk as well as malnutrition diagnosis according to GLIM criteria was observed in 87.8% (n = 374) of patienttritional risk and malnutrition were evaluated using NRS-2002 and GLIM criteria. Its concordance was further evaluated by using a Kappa test. Ws. Tools showed a strong concordance (κ= 0.732). All anthropometric data, except for height, were found to be significantly different between patients with moderate and severe malnutrition (p < 0.05). Our findings highlight a high prevalence of malnutrition in this group of hospitalized patients in Mexico. NRS-2002 demonstrated good agreement with the diagnosis of malnutrition according to GLIM criteria and could be considered part of the straightforward two-step approach for malnutrition; however, further studies are needed.


Assuntos
Hospitalização , Desnutrição , Avaliação Nutricional , Estado Nutricional , Humanos , Masculino , Desnutrição/epidemiologia , Desnutrição/diagnóstico , Estudos Transversais , Estudos Retrospectivos , Feminino , Prevalência , Pessoa de Meia-Idade , Idoso , Adulto , Fatores de Risco , Programas de Rastreamento/métodos , Índice de Massa Corporal , Idoso de 80 Anos ou mais
2.
Exp Hematol ; 135: 104232, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38729553

RESUMO

The bone marrow (BM) niche is a complex microenvironment that provides the signals required for regulation of hematopoietic stem cells (HSCs) and the process of hematopoiesis they are responsible for. Bioengineered models of the BM niche incorporate various elements of the in vivo BM microenvironment, including cellular components, soluble factors, a three-dimensional environment, mechanical stimulation of included cells, and perfusion. Recent advances in the bioengineering field have resulted in a spate of new models that shed light on BM function and are approaching precise imitation of the BM niche. These models promise to improve our understanding of the in vivo microenvironment in health and disease. They also aim to serve as platforms for HSC manipulation or as preclinical models for screening novel therapies for BM-associated disorders and diseases.


Assuntos
Medula Óssea , Hematopoese , Células-Tronco Hematopoéticas , Nicho de Células-Tronco , Humanos , Animais , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Medula Óssea/metabolismo , Modelos Biológicos , Células da Medula Óssea/metabolismo , Células da Medula Óssea/citologia
3.
Adv Healthc Mater ; 13(15): e2302074, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38499190

RESUMO

Atherosclerosis still represents a major driver of cardiovascular diseases worldwide. Together with accumulation of lipids in the plaque, inflammation is recognized as one of the key players in the formation and development of atherosclerotic plaque. Systemic anti-inflammatory treatments are successful in reducing the disease burden, but are correlated with severe side effects, underlining the need for targeted formulations. In this work, curcumin is chosen as the anti-inflammatory payload model and further loaded in lignin-based nanoparticles (NPs). The NPs are then coated with a tannic acid (TA)- Fe (III) complex and further cloaked with fragments derived from platelet cell membrane, yielding NPs with homogenous size. The two coatings increase the interaction between the NPs and cells, both endothelial and macrophages, in steady state or inflamed status. Furthermore, NPs are cytocompatible toward endothelial, smooth muscle and immune cells, while not inducing immune activation. The anti-inflammatory efficacy is demonstrated in endothelial cells by real-time quantitative polymerase chain reaction and ELISA assay where curcumin-loaded NPs decrease the expression of Nf-κb, TGF-ß1, IL-6, and IL-1ß in lipopolysaccharide-inflamed cells. Overall, due to the increase in the cell-NP interactions and the anti-inflammatory efficacy, these NPs represent potential candidates for the targeted anti-inflammatory treatment of atherosclerosis.


Assuntos
Anti-Inflamatórios , Aterosclerose , Plaquetas , Curcumina , Nanopartículas , Curcumina/química , Curcumina/farmacologia , Aterosclerose/tratamento farmacológico , Humanos , Nanopartículas/química , Plaquetas/metabolismo , Plaquetas/efeitos dos fármacos , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/administração & dosagem , Animais , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Células Endoteliais da Veia Umbilical Humana , Taninos/química , Taninos/farmacologia , Células RAW 264.7 , Camundongos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo
5.
Enzyme Microb Technol ; 174: 110375, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38157781

RESUMO

To understand the influence of family 3 Carbohydrate Binding Module (hereafter CBM3), single (GH5 cellulase; CelB, CelBΔCBM), bi-chimeric [GH26 endo-mannanase (ManB-1601) and GH11 endo-xylanase (XynB); ManB-XynB [1], ManB-XynB-CBM] and tri-chimeric [ManB-XynB-CelB [1], ManB-XynB-CelBΔCBM] enzyme variants (fused or deleted of CBM) were produced and purified to homogeneity. CBM3 did not alter the pH and temperature optima of bi- and tri-chimeric enzymes but improved the pH and temperature stability of ManB in CBM variants of bi-/tri-chimeric enzymes. Truncation of CBM in CelB shifted the pH optimum and increased the melting temperature (Tm 65 â„ƒ). CBM3 improved both substrate affinity (Km) and catalytic efficiency (kcat/Km) of fused enzymes in tri-chimera and CelB but only Km for bi-chimera. Far-UV CD of CelB and bi- and tri-chimeric enzymes suggested that CBM3 improved the α-helical content and compactness in the native state but did not prevent disintegration of secondary structural contents at acidic pH. Steady-state fluorescence studies suggested that under acidic conditions CBM3 prevented the exposure of hydrophobic patches in bi-chimeric protein but could not avert the opening up of chimeric enzyme structure. Aqueous enzyme assisted treatment of mature coconut kernel using single, bi- and tri-chimeric enzymes led to cracks, peeling and fracturing of the matrix and improved the oil yield by up to 22%.


Assuntos
beta-Manosidase , Óleo de Coco , Hidrólise , beta-Manosidase/metabolismo , Temperatura , Proteínas Recombinantes de Fusão
6.
Am J Trop Med Hyg ; 110(4_Suppl): 38-43, 2024 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-38118171

RESUMO

Several temperate countries have used mass chemoprevention interventions with medicines of the 8-aminoquinoline class that prevent relapses from Plasmodium vivax before peak transmission to reduce transmission of malaria. The WHO commissioned a systematic review of the literature and evidence synthesis to inform development of recommendations regarding this intervention referred to as "mass relapse prevention" (MRP). Electronic databases were searched, 866 articles screened, and 25 assessed for eligibility after a full-text review. Two nonrandomized studies were included, one from the Democratic People's Republic of Korea (391,357 participants) and the second from the Azerbaijan Soviet Socialist Republic (∼30,000 participants). The two studies administered a single round of primaquine over 14 days (0.25 mg/kg per day). From 1 to 3 months after the treatment round, the incidence of P. vivax infections was significantly lower in areas that received MRP than those that did not (pooled rate ratio [RR] 0.08, 95% CI 0.07-0.08). At 4 to 12 months after the treatment round, the prevalence of P. vivax infection was significantly lower in MRP villages than non-MRP villages (odds ratio 0.12, 95% CI 0.03-0.52). No severe adverse events were found. The certainty of evidence for all outcomes was very low and no conclusions as to the effectiveness or safety of MRP could be drawn. However, it is not likely that this intervention will be needed in the future as most temperate countries where P. vivax is transmitted are nearing or have already eliminated malaria.


Assuntos
Antimaláricos , Malária Vivax , Plasmodium vivax , Humanos , Malária Vivax/prevenção & controle , Malária Vivax/transmissão , Malária Vivax/epidemiologia , Antimaláricos/uso terapêutico , Prevenção Secundária/métodos , Primaquina/uso terapêutico , Recidiva
7.
Int J Mol Sci ; 24(24)2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38139247

RESUMO

Previously, studies have shown that leukemic cells exhibit elevated glycolytic metabolism and oxidative phosphorylation in comparison to hematopoietic stem cells. These metabolic processes play a crucial role in the growth and survival of leukemic cells. Due to the metabolic plasticity of tumor cells, the use of natural products has been proposed as a therapeutic alternative due to their ability to attack several targets in tumor cells, including those that could modulate metabolism. In this study, the potential of Petiveria alliacea to modulate the metabolism of K562 cell lysates was evaluated by non-targeted metabolomics. Initially, in vitro findings showed that P. alliacea reduces K562 cell proliferation; subsequently, alterations were observed in the endometabolome of cell lysates treated with the extract, mainly in glycolytic, phosphorylative, lipid, and amino acid metabolism. Finally, in vitro assays were performed, confirming that P. Alliacea extract decreased the oxygen consumption rate and intracellular ATP. These results suggest that the anti-tumor activity of the aqueous extract on the K562 cell line is attributed to the decrease in metabolites related to cell proliferation and/or growth, such as nucleotides and nucleosides, leading to cell cycle arrest. Our results provide a preliminary part of the mechanism for the anti-tumor and antiproliferative effects of P. alliacea on cancer.


Assuntos
Leucemia Mieloide , Phytolaccaceae , Humanos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Células K562 , Leucemia Mieloide/tratamento farmacológico , Phytolaccaceae/química
8.
Front Mol Biosci ; 10: 1235160, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38028534

RESUMO

Acute leukemias (AL) are aggressive neoplasms with high mortality rates. Metabolomics and oxidative status have emerged as important tools to identify new biomarkers with clinical utility. To identify the metabolic differences between healthy individuals (HI) and patients with AL, a multiplatform untargeted metabolomic and lipidomic approach was conducted using liquid and gas chromatography coupled with quadrupole-time-of-flight mass spectrometry (LC-QTOF-MS or GC-QTOF-MS). Additionally, the total antioxidant capacity (TAC) was measured. A total of 20 peripheral blood plasma samples were obtained from patients with AL and 18 samples from HI. Our analysis revealed 135 differentially altered metabolites in the patients belonging to 12 chemical classes; likewise, the metabolic pathways of glycerolipids and sphingolipids were the most affected in the patients. A decrease in the TAC of the patients with respect to the HI was evident. This study conducted with a cohort of Colombian patients is consistent with observations from other research studies that suggest dysregulation of lipid compounds. Furthermore, metabolic differences between patients and HI appear to be independent of lifestyle, race, or geographic location, providing valuable information for future advancements in understanding the disease and developing more global therapies.

9.
Cancers (Basel) ; 15(22)2023 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-38001725

RESUMO

Prostate cancer is a significant global health concern, and its prevalence is increasing worldwide. Despite extensive research efforts, the complexity of the disease remains challenging with respect to fully understanding it. Metabolomics has emerged as a powerful approach to understanding prostate cancer by assessing comprehensive metabolite profiles in biological samples. In this study, metabolic profiles of patients with benign prostatic hyperplasia (BPH), prostate cancer (PCa), and metastatic prostate cancer (Met) were characterized using an untargeted approach that included metabolomics and lipidomics via liquid chromatography and gas chromatography coupled with high-resolution mass spectrometry. Comparative analysis among these groups revealed distinct metabolic profiles, primarily associated with lipid biosynthetic pathways, such as biosynthesis of unsaturated fatty acids, fatty acid degradation and elongation, and sphingolipid and linoleic acid metabolism. PCa patients showed lower levels of amino acids, glycerolipids, glycerophospholipids, sphingolipids, and carnitines compared to BPH patients. Compared to Met patients, PCa patients had reduced metabolites in the glycerolipid, glycerophospholipid, and sphingolipid groups, along with increased amino acids and carbohydrates. These altered metabolic profiles provide insights into the underlying pathways of prostate cancer's progression, potentially aiding the development of new diagnostic, and therapeutic strategies.

10.
Front Mol Biosci ; 10: 1206074, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37818099

RESUMO

Chagas disease (ChD), caused by Trypanosoma cruzi, is endemic in American countries and an estimated 8 million people worldwide are chronically infected. Currently, only two drugs are available for therapeutic use against T. cruzi and their use is controversial due to several disadvantages associated with side effects and low compliance with treatment. Therefore, there is a need to search for new tripanocidal agents. Natural products have been considered a potential innovative source of effective and selective agents for drug development to treat T. cruzi infection. Recently, our research group showed that hexanic extract from Clethra fimbriata (CFHEX) exhibits anti-parasitic activity against all stages of T. cruzi parasite, being apoptosis the main cell death mechanism in both epimastigotes and trypomastigotes stages. With the aim of deepening the understanding of the mechanisms of death induced by CFHEX, the metabolic alterations elicited after treatment using a multiplatform metabolomics analysis (RP/HILIC-LC-QTOF-MS and GC-QTOF-MS) were performed. A total of 154 altered compounds were found significant in the treated parasites corresponding to amino acids (Arginine, threonine, cysteine, methionine, glycine, valine, proline, isoleucine, alanine, leucine, glutamic acid, and serine), fatty acids (stearic acid), glycerophospholipids (phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine), sulfur compounds (trypanothione) and carboxylic acids (pyruvate and phosphoenolpyruvate). The most affected metabolic pathways were mainly related to energy metabolism, which was found to be decrease during the evaluated treatment time. Further, exogenous compounds of the triterpene type (betulinic, ursolic and pomolic acid) previously described in C. fimbriata were found inside the treated parasites. Our findings suggest that triterpene-type compounds may contribute to the activity of CFHEX by altering essential processes in the parasite.

11.
Int J Mol Sci ; 24(16)2023 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-37629156

RESUMO

The poor response, adverse effects and drug resistance to treatment of acute myeloid leukemia (AML) have led to searching for safer and more effective therapeutic alternatives. We previously demonstrated that the alcoholic extract of Petiveria alliacea (Esperanza) has a significant in vitro antitumor effect on other tumor cells and also the ability to regulate energy metabolism. We evaluated the effect of the Esperanza extract in vitro and in vivo in a murine model of AML with DA-3/ER-GM cells. First, a chemical characterization of the extract was conducted through liquid and gas chromatography coupled with mass spectrometry. In vitro findings showed that the extract modulates tumor metabolism by decreasing glucose uptake and increasing reactive oxygen species, which leads to a reduction in cell proliferation. Then, to evaluate the effect of the extract in vivo, we standardized the mouse model by injecting DA-3/ER-GM cells intravenously. The animals treated with the extract showed a lower percentage of circulating blasts, higher values of hemoglobin, hematocrit, and platelets, less infiltration of blasts in the spleen, and greater production of cytokines compared to the control group. These results suggest that the antitumor activity of this extract on DA-3/ER-GM cells can be attributed to the decrease in glycolytic metabolism, its activity as a mitocan, and the possible immunomodulatory effect by reducing tumor proliferation and metastasis.


Assuntos
Leucemia Mieloide , Phytolaccaceae , Animais , Camundongos , Carga Tumoral , Cromatografia Gasosa-Espectrometria de Massas , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
12.
Clinics (Sao Paulo) ; 78: 100242, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37480642

RESUMO

BACKGROUND: The 6-OHDA nigro-striatal lesion model has already been related to disorders in the excitability and synchronicity of neural networks and variation in the expression of transmembrane proteins that control intra and extracellular ionic concentrations, such as cation-chloride cotransporters (NKCC1 and KCC2) and Na+/K+-ATPase and, also, to the glial proliferation after injury. All these non-synaptic mechanisms have already been related to neuronal injury and hyper-synchronism processes. OBJECTIVE: The main objective of this study is to verify whether mechanisms not directly related to synaptic neurotransmission could be involved in the modulation of nigrostriatal pathways. METHODS: Male Wistar rats, 3 months old, were submitted to a unilateral injection of 24 µg of 6-OHDA, in the striatum (n = 8). The animals in the Control group (n = 8) were submitted to the same protocol, with the replacement of 6-OHDA by 0.9% saline. The analysis by optical densitometry was performed to quantify the immunoreactivity intensity of GFAP, NKCC1, KCC2, Na+/K+-ATPase, TH and Cx36. RESULTS: The 6-OHDA induced lesions in the striatum, were not followed by changes in the expression cation-chloride cotransporters and Na+/K+-ATPase, but with astrocytic reactivity in the lesioned and adjacent regions of the nigrostriatal. Moreover, the dopaminergic degeneration caused by 6-OHDA is followed by changes in the expression of connexin-36. CONCLUSIONS: The use of the GJ blockers directly along the nigrostriatal pathways to control PD motor symptoms is conjectured. Electrophysiology of the striatum and the substantia nigra, to verify changes in neuronal synchronism, comparing brain slices of control animals and experimental models of PD, is needed.


Assuntos
Doença de Parkinson , Simportadores , Ratos , Animais , Masculino , Oxidopamina , Ratos Wistar , Cloretos , Modelos Animais de Doenças , Adenosina Trifosfatases
13.
Metabolites ; 13(7)2023 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-37512495

RESUMO

Over the past decades, Colombia has suffered complex social problems related to illicit crops, including forced displacement, violence, and environmental damage, among other consequences for vulnerable populations. Considerable effort has been made in the regulation of illicit crops, predominantly Cannabis sativa, leading to advances such as the legalization of medical cannabis and its derivatives, the improvement of crops, and leaving an open window to the development of scientific knowledge to explore alternative uses. It is estimated that C. sativa can produce approximately 750 specialized secondary metabolites. Some of the most relevant due to their anticancer properties, besides cannabinoids, are monoterpenes, sesquiterpenoids, triterpenoids, essential oils, flavonoids, and phenolic compounds. However, despite the increase in scientific research on the subject, it is necessary to study the primary and secondary metabolism of the plant and to identify key pathways that explore its great metabolic potential. For this purpose, a genome-scale metabolic reconstruction of C. sativa is described and contextualized using LC-QTOF-MS metabolic data obtained from the leaf extract from plants grown in the region of Pesca-Boyaca, Colombia under greenhouse conditions at the Clever Leaves facility. A compartmentalized model with 2101 reactions and 1314 metabolites highlights pathways associated with fatty acid biosynthesis, steroids, and amino acids, along with the metabolism of purine, pyrimidine, glucose, starch, and sucrose. Key metabolites were identified through metabolomic data, such as neurine, cannabisativine, cannflavin A, palmitoleic acid, cannabinoids, geranylhydroquinone, and steroids. They were analyzed and integrated into the reconstruction, and their potential applications are discussed. Cytotoxicity assays revealed high anticancer activity against gastric adenocarcinoma (AGS), melanoma cells (A375), and lung carcinoma cells (A549), combined with negligible impact against healthy human skin cells.

14.
Ther Innov Regul Sci ; 57(4): 875-885, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37072651

RESUMO

Project Orbis was initiated in May 2019 by the Oncology Center of Excellence to facilitate faster patient access to innovative cancer therapies by providing a framework for concurrent submissions and review of oncology products among international partners. Since its inception, Australia's Therapeutic Goods Administration (TGA), Canada's Health Canada (HC), Singapore's Health Sciences Authority (HSA), Switzerland's Swissmedic (SMC), Brazil's National Health Surveillance Agency (ANVISA), United Kingdom's Medicines and Healthcare Products Regulatory Agency (MHRA), and most recently Israel's Ministry of Health (IMoH) Medical Technologies, Health Information, Innovation and Research (MTIIR) Directorate, have joined Project Orbis. While each country has its own expedited review pathways to bring promising therapies to patients, there are some similarities and differences in pathways and timelines. FDA's fast-track designation and MHRA's marketing authorization under exceptional circumstances (MAEC) allow non-clinical and limited clinical evidence to support approval under these programs. HC's Extraordinary Use New Drug (EUND) pathway allows granting exceptional use authorization with limited clinical evidence. ANVISA, HSA, MTIIR, and TGA do not have standard pathways that allow non-clinical evidence and limited clinical evidence. While there is no definite regulatory pathway for HSA, the current framework for approval does allow flexibility in the type of data (non-clinical or clinical) required to demonstrate the benefit-risk profile of a product. HSA may register a product if the agency is satisfied that the overall benefit outweighs the risk. All Project Orbis Partner (POP) countries have similar programs to the FDA accelerated approval program except ANVISA. Although HSA and MTIIR do not have defined pathways for accelerated approval programs, there are opportunities to request accelerated approval per these agencies. All POP countries have pathways like the FDA priority review except MHRA. Priority review timelines for new drugs range from 120 to 264 calendar days (cd). Standard review timelines for new drugs range from 180 to 365 cd.


Assuntos
Medicina , Neoplasias , Estados Unidos , Humanos , Aprovação de Drogas , United States Food and Drug Administration , Canadá
15.
Nat Commun ; 14(1): 753, 2023 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-36765065

RESUMO

Mesenchymal stromal cells (MSCs) are multipotent progenitor cells that are of considerable clinical potential in transplantation and anti-inflammatory therapies due to their capacity for tissue repair and immunomodulation. However, MSCs rapidly differentiate once in culture, making their large-scale expansion for use in immunomodulatory therapies challenging. Although the differentiation mechanisms of MSCs have been extensively investigated using materials, little is known about how materials can influence paracrine activities of MSCs. Here, we show that nanotopography can control the immunomodulatory capacity of MSCs through decreased intracellular tension and increasing oxidative glycolysis. We use nanotopography to identify bioactive metabolites that modulate intracellular tension, growth and immunomodulatory phenotype of MSCs in standard culture and during larger scale cell manufacture. Our findings demonstrate an effective route to support large-scale expansion of functional MSCs for therapeutic purposes.


Assuntos
Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Multipotentes/metabolismo , Diferenciação Celular , Imunomodulação , Fenótipo
16.
Gut ; 72(3): 535-548, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36109153

RESUMO

OBJECTIVE: GATA6 is a key regulator of the classical phenotype in pancreatic ductal adenocarcinoma (PDAC). Low GATA6 expression associates with poor patient outcome. GATA4 is the second most expressed GATA factor in the pancreas. We assessed whether, and how, GATA4 contributes to PDAC phenotype and analysed the association of expression with outcome and response to chemotherapy. DESIGN: We analysed PDAC transcriptomic data, stratifying cases according to GATA4 and GATA6 expression and identified differentially expressed genes and pathways. The genome-wide distribution of GATA4 was assessed, as well as the effects of GATA4 knockdown. A multicentre tissue microarray study to assess GATA4 and GATA6 expression in samples (n=745) from patients with resectable was performed. GATA4 and GATA6 levels were dichotomised into high/low categorical variables; association with outcome was assessed using univariable and multivariable Cox regression models. RESULTS: GATA4 messenger RNA is enriched in classical, compared with basal-like tumours. We classified samples in 4 groups as high/low for GATA4 and GATA6. Reduced expression of GATA4 had a minor transcriptional impact but low expression of GATA4 enhanced the effects of GATA6 low expression. GATA4 and GATA6 display a partially overlapping genome-wide distribution, mainly at promoters. Reduced expression of both proteins in tumours was associated with the worst patient survival. GATA4 and GATA6 expression significantly decreased in metastases and negatively correlated with basal markers. CONCLUSIONS: GATA4 and GATA6 cooperate to maintain the classical phenotype. Our findings provide compelling rationale to assess their expression as biomarkers of poor prognosis and therapeutic response.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/patologia , Pâncreas/patologia , Carcinoma Ductal Pancreático/patologia , Perfilação da Expressão Gênica , Fator de Transcrição GATA6/genética , Fator de Transcrição GATA4/genética , Fator de Transcrição GATA4/metabolismo
17.
Clinics ; 78: 100242, 2023. graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1506005

RESUMO

Abstract Background The 6-OHDA nigro-striatal lesion model has already been related to disorders in the excitability and synchronicity of neural networks and variation in the expression of transmembrane proteins that control intra and extracellular ionic concentrations, such as cation-chloride cotransporters (NKCC1 and KCC2) and Na+/K+-ATPase and, also, to the glial proliferation after injury. All these non-synaptic mechanisms have already been related to neuronal injury and hyper-synchronism processes. Objective The main objective of this study is to verify whether mechanisms not directly related to synaptic neurotransmission could be involved in the modulation of nigrostriatal pathways. Methods Male Wistar rats, 3 months old, were submitted to a unilateral injection of 24 µg of 6-OHDA, in the striatum (n= 8). The animals in the Control group (n= 8) were submitted to the same protocol, with the replacement of 6-OHDA by 0.9% saline. The analysis by optical densitometry was performed to quantify the immunoreactivity intensity of GFAP, NKCC1, KCC2, Na+/K+-ATPase, TH and Cx36. Results The 6-OHDA induced lesions in the striatum, were not followed by changes in the expression cation-chloride cotransporters and Na+/K+-ATPase, but with astrocytic reactivity in the lesioned and adjacent regions of the nigrostriatal. Moreover, the dopaminergic degeneration caused by 6-OHDA is followed by changes in the expression of connexin-36. Conclusions The use of the GJ blockers directly along the nigrostriatal pathways to control PD motor symptoms is conjectured. Electrophysiology of the striatum and the substantia nigra, to verify changes in neuronal synchronism, comparing brain slices of control animals and experimental models of PD, is needed.

18.
Acta odontol. latinoam ; 35(3): 188-197, Dec. 2022. graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1419945

RESUMO

ABSTRACT Eighth-generation adhesives may be applied with total etch, selective-etch or self-conditioning, and serve as primers for non-dental substrates. Aim: To determine the bonding characteristics of universal adhesives applied to the deep pulp wall with different strategies, by means of shear bond strength and laser microscopy. Materials and Method: Cavities 4 mm deep and maximum width were carved in 36 extracted molars. Nine groups were formed according to dental substrate treatment and adhesives, as follows: Total-etch: group 1-Monobond 7 self-etch, group 2-One coat 7 universal, and group 3-Single bond universal; Adamantine etch: group 4-Monobond 7 self-etch, group 5-One coat 7 universal, and group 6-Single bond universal; Self-conditioning: group 7-Monobond 7 self-etch, group 8-One coat 7 universal, and group 9-Single bond universal. Molars were filled following the manufacturer's instructions. Three specimens per group (27 altogether) were used to determine shear bond strength using a universal testing machine, while layer thicknesses were measured on the remaining specimens using microscope images and Olympus LEXT 3D Software. Analysis of variance was used to compare data. Results: Mean (standard deviation) bond strength in megapascals (MPa) was: group 1: 7.06±3.01; group 2: 10.74±4.36; group 3: 8.20±3.92; group 4: 7.41±2.23; group 5: 6.84±1.50; group 6: 5.86±2.10; group 7: 5.83±1.94; group 8: 7.14±2.37; group 9: 8.06±3.51. Bond strength was higher (p=0.049) for total-etch (8.61±3.96) than for selective etch (6.71±1.98) and self-conditioning (6.91±2.68). No significant difference was found among the three adhesives (p=0.205). Adhesive layer in micrometers (μm) was total-etch 8.71±4.93, selective etch 5.49±1.70 and self-conditioning 6.27±3.01, with no significant difference. Conclusions: There were significant differences among bonding strategies, with the highest values for total-etch. No significant difference was observed between self-conditioning and selective etch. No significant difference was found among the adhesives, which all behaved similarly. The greatest adhesive layer thicknesses were recorded in the total-etch group, with no significant difference among the various adhesive approaches.


RESUMEN Los adhesivos universales de octava generación pueden ser aplicados con diferentes estrategias de unión: grabado total, grabado selectivo o autoacondicionamiento. Además, imprimen sustratos no dentales. Objetivo: Determinar las caracteristicas de unión de adhesivos universales con diferentes estrategias en pared pulpar profunda mediante resistencia adhesiva al corte y microscopía laser. Materiales y Método: En 36 molares se tallaron cavidades de 4 mm de profundidad y ancho máximo. Se dividieron en 9 grupos según tratamientos y adhesivos. Grabado total: grupo 1-Monobond 7 self-etching, grupo 2-One coat 7 universal y grupo 3-Single bond universal; Grabado selectivo: grupo 4-Monobond 7 self-etching; grupo 5-One coat 7 universal y grupo 6-Single bond universal y Autoacondicionamiento: grupo 7-Monobond 7 self-etching; grupo 8-One coat 7 universal y grupo 9-Single bond universal. Las obturaciones se realizaron siguiendo las instrucciones del fabricante. La resistencia adhesiva al corte se determinó utilizando una máquina de ensayo universal sobre 27 especímenes mientras que los restantes fueron empleados para evaluar los espesores de la capa generado sobre imágenes obtenidas con microscopía y con el software Olympus LEXT 3D. Se ultilizó análisis de varianza. Resultados: Resistencia adhesiva en megapascal (MPa) media (desviación estándar): grupo 1: 7,06±3,01; grupo 2: 10,74±4,36; grupo 3: 8,20±3,92; grupo 4: 7,41±2,23; grupo 5: 6,84±1,50; grupo 6: 5,86±2,10; grupo 7: 5,83±1,94; grupo 8: 7,14±2,37; grupo 9: 8,06±3,51. Grabado total (8,61±3,96) registró los valores mayores (p=0,049) en comparación a grabado selectivo (6,71±1,98) y autoacondicionamiento (6,91±2,68). Los adhesivos no tuvieron diferencias significativas (p=0,205). Capa adhesiva en μm: Grabado total (8,71±4,93); grabado selectivo (5,49±1,70) y autoacondicionamiento (6,27±3,01) sin diferencias significativas (p=0,073). Conclusiones: Las estrategias de unión mostraron diferencias significativas; los valores más altos se obtuvieron con grabado total y entre autoacondicionamiento y grabado selectivo no hubo significancia. Los adhesivos evidenciaron comportamientos similares sin registrar diferencias significativas. Los mayores espesores de capa fueron con grabado total sin diferencias significativas entre las técnicas.

19.
Clin Exp Dent Res ; 8(5): 1028-1034, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35707842

RESUMO

OBJECTIVES: This study examined the variation in prevalence of periodontitis among different sexes, age groups, smoking status, and oral hygiene adherence in patients affected by either Crohn's disease (CD) or ulcerative colitis (UC). MATERIALS & METHODS: This study was a retrospective chart analysis that collected data from the School of Dentistry's Oral Health Clinic at the University of Alberta, Edmonton, Canada. Patients' electronic health records between the years of 2013 and 2019 were analyzed. Multiple keywords such as IBD, CD, UC, and periodontal disease with various spelling combinations were used for searching and gathering pertinent data, which was then further assessed. After applying the inclusion and exclusion criteria, a total of 80 patient charts were included. These patient charts were thoroughly screened to gather information such as age, sex, smoking status, and a variety of periodontal parameters. Collected data were analyzed using SPSS software by using Pearson's χ2 , Pearson's correlation, and Mann-Whitney U-test. RESULTS: IBD had an impact on the severity of periodontitis in patients between the ages of 50 and 64 years with higher odds ratio (OR). Biological sex or history of smoking in IBD patients did not have higher odds of developing periodontitis. Plaque score derived from this retrospective study was used to estimate the patient's oral hygiene status and showed no impact. Also, prevalence of periodontitis did not differ between UC and CD. We anticipated some of these findings because of the retrospective nature of the study. CONCLUSIONS: Within the limitation of the retrospective study, IBD patients in the 50-64 age group years showed a higher odds ratio for a greater prevalence of periodontitis. Thus, a closer periodontal recall and evaluation in these patients is recommended for early diagnosis and preventive care. It is advised that periodontists work closely with gastroenterologists to maintain periodontal health in IBD-affected individuals.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Periodontite , Doença Crônica , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/epidemiologia , Doença de Crohn/diagnóstico , Doença de Crohn/epidemiologia , Humanos , Pessoa de Meia-Idade , Higiene Bucal , Periodontite/epidemiologia , Estudos Retrospectivos
20.
Sci Adv ; 8(23): eabn3328, 2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35675391

RESUMO

In 1995, journalist Gary Taubes published an article in Science titled "Epidemiology faces its limits," which questioned the utility of nonrandomized epidemiologic research and has since been cited more than 1000 times. He highlighted numerous examples of research topics he viewed as having questionable merit. Studies have since accumulated for these associations. We systematically evaluated current evidence of 53 example associations discussed in the article. Approximately one-quarter of those presented as doubtful are now widely viewed as causal based on current evaluations of the public health consensus. They include associations between alcohol consumption and breast cancer, residential radon exposure and lung cancer, and the use of tanning devices and melanoma. This history should inform current debates about the reproducibility of epidemiologic research results.

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