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1.
Int J Mol Sci ; 25(5)2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38474255

RESUMO

Linagliptin is a selective dipeptidyl peptidase-4 (DPP-4) inhibitor that indirectly elevates the glucagon-like peptide-1 (GLP-1) level. The aim of the present study was to check whether linagliptin has an influence on neurotransmission in rat brain. Rats were acutely and chronically exposed to linagliptin (10 and 20 mg/kg, intraperitoneally (i.p.)). Twenty-four hours later, the striatum and hippocampus were selected for further studies. In neurochemical experiments, using high-performance liquid chromatography with electrochemical detection (HPLC-ED), the concentrations of three major neurotransmitters-dopamine, serotonin and noradrenaline-and their metabolites were measured. The analysis of mRNA expression of dopamine (D1 and D2), serotonin (5-HT-1 and 5-HT-2) and noradrenaline (α1 and α2a) receptors was also investigated using real-time quantitative reverse transcription polymerase chain reaction (RQ-PCR) in the same brain areas. Linagliptin has the ability to influence the dopaminergic system. In the striatum, the elevation of dopamine and its metabolites was observed after repeated administration of that linagliptin, and in the hippocampus, a reduction in dopamine metabolism was demonstrated. Acute linagliptin exposure increases the serotonin level in both areas, while after chronic linagliptin administration a tendency for the mRNA expression of serotoninergic receptors (5-HT1A and 5-HT2A) to increase was observed. A single instance of exposure to linagliptin significantly modified the noradrenaline level in the striatum and intensified noradrenaline turnover in the hippocampus. The recognition of the interactions in the brain between DPP-4 inhibitors and neurotransmitters and/or receptors is a crucial step for finding novel discoveries in the pharmacology of DPP-4 inhibitors and raises hope for further applications of DPP-4 inhibitors in clinical practices.


Assuntos
Inibidores da Dipeptidil Peptidase IV , Linagliptina , Ratos , Animais , Linagliptina/farmacologia , Inibidores da Dipeptidil Peptidase IV/farmacologia , Serotonina , Dopamina , Norepinefrina , Dipeptidil Peptidase 4/metabolismo , Hipocampo/metabolismo , Neurotransmissores , RNA Mensageiro
2.
Molecules ; 28(16)2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37630316

RESUMO

The exposure of humans to fluorine is connected with its presence in the air, food and water. It is well known that fluorides even at a low concentration but with long time exposure accumulate in the body and lead to numerous metabolic disorders. Fluoride is recognised as a factor modulating the energy metabolism of cells. This interaction is of particular importance in muscle cells, which are cells with high metabolic activity related to the metabolism of glucose and glycogen. In someone suffering from chronic fluoride poisoning, frequent symptoms are chronic fatigue not relieved by extra sleep or rest, muscular weakness, muscle spasms, involuntary twitching. The aim of this study was to examine the effect of fluorine at concentrations determined in blood of people environmentally exposed to fluorides on activity and expression of enzymes taking part in metabolism of muscle glycogen. CCL136 cells were cultured under standard conditions with the addition of NaF. The amount of ATP produced by the cells was determined using the HPLC method, the amount and expression of genes responsible for glycogen metabolism using WB and RT PCR methods and the amount of glycogen in cells using the fluorimetric and PAS methods. It has been shown that in CCL136 cells exposed to 1, 3 and 10 µM NaF there is a change in the energy state and expression pattern of enzymes involved in the synthesis and breakdown of glycogen. It was observed that NaF caused a decrease in ATP content in CCL136 cells. Fluoride exposure also increased glycogen deposition. These changes were accompanied by a decrease in gene expression and the level of enzymatic proteins related to glycogen metabolism: glycogen synthase, glycogen synthase kinase and glycogen phosphorylase. The results obtained shed new light on the molecular mechanisms by which fluoride acts as an environmental toxin.


Assuntos
Fluoretos , Flúor , Humanos , Fluoretos/farmacologia , Fibras Musculares Esqueléticas , Glicogênio , Linhagem Celular , Trifosfato de Adenosina
3.
Cancers (Basel) ; 15(7)2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-37046844

RESUMO

One area of glioblastoma research is the metabolism of tumor cells and detecting differences between tumor and healthy brain tissue metabolism. Here, we review differences in fatty acid metabolism, with a particular focus on the biosynthesis of saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA) by fatty acid synthase (FASN), elongases, and desaturases. We also describe the significance of individual fatty acids in glioblastoma tumorigenesis, as well as the importance of glycerophospholipid and triacylglycerol synthesis in this process. Specifically, we show the significance and function of various isoforms of glycerol-3-phosphate acyltransferases (GPAT), 1-acylglycerol-3-phosphate O-acyltransferases (AGPAT), lipins, as well as enzymes involved in the synthesis of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI), and cardiolipin (CL). This review also highlights the involvement of diacylglycerol O-acyltransferase (DGAT) in triacylglycerol biosynthesis. Due to significant gaps in knowledge, the GEPIA database was utilized to demonstrate the significance of individual enzymes in glioblastoma tumorigenesis. Finally, we also describe the significance of lipid droplets in glioblastoma and the impact of fatty acid synthesis, particularly docosahexaenoic acid (DHA), on cell membrane fluidity and signal transduction from the epidermal growth factor receptor (EGFR).

4.
Int J Mol Sci ; 24(4)2023 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-36835171

RESUMO

Burns and their treatment are a significant medical problem. The loss of the physical barrier function of the skin opens the door to microbial invasion and can lead to infection. The repair process of the damage caused by the burn is impaired due to the enhanced loss of fluids and minerals through the burn wound, the onset of hypermetabolism with the concomitant disruption of nutrient supply, and derangements in the endocrine system. In addition, the initiated inflammatory and free radical processes drive the progression of oxidative stress, the inhibition of which largely depends on an adequate supply of antioxidants and minerals. Clinical experience and research provide more and more data to make the treatment of patients with thermal injury increasingly effective. The publication discusses disorders occurring in patients after thermal injury and the methods used at various stages of treatment.


Assuntos
Queimaduras , Humanos , Queimaduras/tratamento farmacológico , Antioxidantes/farmacologia , Estresse Oxidativo , Pele/metabolismo , Sistema Endócrino
5.
Int J Mol Sci ; 24(2)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36675073

RESUMO

The purpose of this review is to attempt to outline the potential role of fluoride in the pathogenesis of brain tumours, including glioblastoma (GBM). In this paper, we show for the first time that fluoride can potentially affect the generally accepted signalling pathways implicated in the formation and clinical course of GBM. Fluorine compounds easily cross the blood-brain barrier. Enhanced oxidative stress, disruption of multiple cellular pathways, and microglial activation are just a few examples of recent reports on the role of fluoride in the central nervous system (CNS). We sought to present the key mechanisms underlying the development and invasiveness of GBM, as well as evidence on the current state of knowledge about the pleiotropic, direct, or indirect involvement of fluoride in the regulation of these mechanisms in various tissues, including neural and tumour tissue. The effects of fluoride on the human body are still a matter of controversy. However, given the growing incidence of brain tumours, especially in children, and numerous reports on the effects of fluoride on the CNS, it is worth taking a closer look at these mechanisms in the context of brain tumours, including gliomas.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Criança , Humanos , Fluoretos/metabolismo , Sistema Nervoso Central/metabolismo , Neoplasias Encefálicas/metabolismo , Glioblastoma/metabolismo , Barreira Hematoencefálica/metabolismo
6.
Biol Trace Elem Res ; 201(2): 728-738, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35551604

RESUMO

The aim of the study was to investigate the distribution of elements (Ca, Mg, Fe, P, Zn, Na, K, Cu, Cr, Mo, Co, Se) analyzed using inductively coupled plasma optical emission spectrometry (ICP-OES) and fluorides (F-) determined potentiometrically using an ion-selective electrode in the enamel of European beaver (Castor fiber) teeth. Material for the study was tooth enamel collected from lower jaws from the skulls of the animals borrowed from museum collections (animals inhabited north-western Poland). The results of our study indicate the important role of F- as an element that can affect the hardness and strength of beaver tooth enamel. Critical to the function of beaver teeth (i.e., shearing and crushing wood) is the presence of elements such as Fe in the central incisor labial aspect (orange layer of the incisor enamel), Mg in the inner side of the incisor enamel, and Co and F- in the enamel of the molars. Thanks to the high content of these elements, the enamel is durable and the teeth are adapted to the nutritional and ecological characteristics of this mammalian species. Our study on the distribution of elements in the enamel of beaver teeth may also be important for the understanding of the enamel mineralization processes, determining how elements change the properties of the materials, and exploring the relationship between the environment and life history of the beaver.


Assuntos
Dente , Oligoelementos , Animais , Fluoretos/análise , Oligoelementos/análise , Roedores , Dente/química , Esmalte Dentário
7.
Nutrients ; 14(20)2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36296932

RESUMO

Burns exceeding 30% of total body surface area (TBSA) result in considerable hypovolemia coupled with the formation and release of inflammatory mediators, leading to subsequent systemic effects known as burn shock. Because of plasma exudation and the associated losses of large quantities of minerals, severe burns can lead to nutritional deficiencies and consequently disrupt homeostasis and metabolism of the entire body. The study group comprised 62 patients, who were divided into 3 groups according to the severity of burns. Serum samples were tested for concentrations of Ca, Mg, Mn, P, K, Zn, Cu, Fe, Se, Na, Cr, Ni, and Al. The mineral concentrations in serum of patients with burn injuries differ significantly from reference values, but this is not affected by the extent of the body burn. There are statistically significant decreases in serum concentrations of elements important for antioxidant protection (Zn, Cu, Se), and significant increases in the concentrations of toxic elements (Al and Ni), which may aggravate the effects associated with the state of burn shock. The Spearman rank correlation analysis did not reveal any statistically significant relationships between the serum concentrations of Mn, Ni, Al, K, Na, P, Mg, Zn, Se, Cr and the affected body surface area and severity of the burn-the values were at the lower end of the reference range. The obtained results indicate that proper nutrition, including elements replenishment, is extremely important in the recovery process of burn patients and time to nutrition is an important factor affecting patient survival after severe burn.


Assuntos
Antioxidantes , Queimaduras , Humanos , Minerais/análise , Hospitalização , Mediadores da Inflamação
8.
Nutrients ; 14(12)2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35745280

RESUMO

Matcha, or powdered green tea (Camellia sinensis) of the Tencha type, is popular all around the world, and its consumption continues to rise. Because of its unique cultivation method, it is rich in phytochemicals and has many health-promoting properties; it contains high concentrations of polyphenols, theanine and chlorophyll. Tea, and by extension matcha, contains numerous minerals, one of which is fluorine. Under physiological conditions, this mineral plays a significant role in hard tissue mineralisation processes. However, even in low concentrations, with prolonged exposure, fluoride can accumulate in the body, leading to a number of harmful effects. The aim of this study was to evaluate, for the first time, the fluoride content of the matcha infusions from different harvests, brewed using water at different temperatures (25 °C, 70 °C, 80 °C and 90 °C). The content of fluoride ions was measured by the potentiometric method. The fluoride content ranged from 3.36 to 4.03 mg/L and was dependent on both the leaf harvest time and brewing temperature. The concentration of this mineral in the dry powder ranged from 118.39 to 121.65 mg/kg. Irrespective of the water temperature or harvest time, matcha was found to have a high fluoride content, with particularly high concentrations being noted in the powder itself.


Assuntos
Camellia sinensis , Fluoretos , Antioxidantes/análise , Folhas de Planta/química , Pós , Chá/química , Água/análise
9.
Int J Mol Sci ; 23(4)2022 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-35216283

RESUMO

Chemokines are a group of about 50 chemotactic cytokines crucial for the migration of immune system cells and tumor cells, as well as for metastasis. One of the 20 chemokine receptors identified to date is CXCR2, a G-protein-coupled receptor (GPCR) whose most known ligands are CXCL8 (IL-8) and CXCL1 (GRO-α). In this article we present a comprehensive review of literature concerning the role of CXCR2 in cancer. We start with regulation of its expression at the transcriptional level and how this regulation involves microRNAs. We show the mechanism of CXCR2 signal transduction, in particular the action of heterotrimeric G proteins, phosphorylation, internalization, intracellular trafficking, sequestration, recycling, and degradation of CXCR2. We discuss in detail the mechanism of the effects of activated CXCR2 on the actin cytoskeleton. Finally, we describe the involvement of CXCR2 in cancer. We focused on the importance of CXCR2 in tumor processes such as proliferation, migration, and invasion of tumor cells as well as the effects of CXCR2 activation on angiogenesis, lymphangiogenesis, and cellular senescence. We also discuss the importance of CXCR2 in cell recruitment to the tumor niche including tumor-associated neutrophils (TAN), tumor-associated macrophages (TAM), myeloid-derived suppressor cells (MDSC), and regulatory T (Treg) cells.


Assuntos
Neoplasias , Receptores de Interleucina-8B , Transdução de Sinais , Quimiocina CXCL1/metabolismo , Quimiocinas/metabolismo , Humanos , Interleucina-8/metabolismo , Neoplasias/genética , Fosforilação , Receptores de Interleucina-8B/genética , Receptores de Interleucina-8B/metabolismo
10.
Int J Mol Sci ; 23(2)2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35054978

RESUMO

CXCL1 is one of the most important chemokines, part of a group of chemotactic cytokines involved in the development of many inflammatory diseases. It activates CXCR2 and, at high levels, CXCR1. The expression of CXCL1 is elevated in inflammatory reactions and also has important functions in physiology, including the induction of angiogenesis and recruitment of neutrophils. Due to a lack of reviews that precisely describe the regulation of CXCL1 expression and function, in this paper, we present the mechanisms of CXCL1 expression regulation with a special focus on cancer. We concentrate on the regulation of CXCL1 expression through the regulation of CXCL1 transcription and mRNA stability, including the involvement of NF-κB, p53, the effect of miRNAs and cytokines such as IFN-γ, IL-1ß, IL-17, TGF-ß and TNF-α. We also describe the mechanisms regulating CXCL1 activity in the extracellular space, including proteolytic processing, CXCL1 dimerization and the influence of the ACKR1/DARC receptor on CXCL1 localization. Finally, we explain the role of CXCL1 in cancer and possible therapeutic approaches directed against this chemokine.


Assuntos
Quimiocina CXCL1/genética , Quimiocina CXCL1/metabolismo , Regulação da Expressão Gênica , Regiões Promotoras Genéticas , Transporte Proteico , Estabilidade de RNA , Animais , Biomarcadores , Proteínas de Transporte , Suscetibilidade a Doenças , Humanos , Hipóxia/genética , Hipóxia/metabolismo , Espaço Intracelular , Especificidade de Órgãos , Ligação Proteica , Proteólise , Interferência de RNA
11.
Pharmaceuticals (Basel) ; 14(12)2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34959734

RESUMO

Aegopodium podagraria L. (goutweed), a member of the Apiaceae family, is a common perennial plant found all around the world that has been used in folk medicine since antiquity. Goutweed leaves contain polyacetylenes, essential oils, mono- and sesquiterpenes, vitamins, macro- and microelements, and phenolic compounds. In spite of its many health-promoting properties, including antioxidant effects, the plant has not been thoroughly studied. The aim of this study was to investigate the antioxidant properties of different goutweed leaf extracts and their effects on the THP-1 cell line, and also to describe the chemical characteristics of goutweed. Falcarinol and falcarindiol and essential oil were determined by gas chromatography coupled with mass spectrometry. Spectrophotometry was used to measure the total content of polyphenols and antioxidant activity-by DPPH and FRAP methods. Oxidative stress in THP-1 cells was induced via sodium fluoride. Then, goutweed leaf extracts were added to evaluate their influence on antioxidant potential (ABTS) and the activity of antioxidant enzymes. Confocal microscopy was used to visualise the production of cytoplasmic and mitochondrial reactive oxygen species (ROS) and for in vitro imaging of apoptosis. The ethanol extracts have a high total content of polyphenols, polyacetylenes, and essential oil, as well as high antioxidant potential. The main volatiles represented diverse chemical groups, which are both oxygenated derivatives of sesquiterpenes and monoterpenes. We also demonstrated positive effects of the high antioxidant potential and increased activity of antioxidant enzymes on cell cultures under severe fluoride-induced oxidative stress. Extraction at 80 ℃ and the use of ethanol as a solvent increased the antioxidant capacity of the extract. The leaves of Aegopodium podagraria may serve as a valuable source of antioxidants in the daily diet and assist in the prevention and treatment of oxidative stress-mediated conditions, e.g., inflammatory conditions, cardiovascular diseases, neurodegenerative diseases, and even obesity.

12.
Int J Mol Sci ; 22(19)2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34639040

RESUMO

Chronic (continuous, non-interrupted) hypoxia and cycling (intermittent, transient) hypoxia are two types of hypoxia occurring in malignant tumors. They are both associated with the activation of hypoxia-inducible factor-1 (HIF-1) and nuclear factor κB (NF-κB), which induce changes in gene expression. This paper discusses in detail the mechanisms of activation of these two transcription factors in chronic and cycling hypoxia and the crosstalk between both signaling pathways. In particular, it focuses on the importance of reactive oxygen species (ROS), reactive nitrogen species (RNS) together with nitric oxide synthase, acetylation of HIF-1, and the action of MAPK cascades. The paper also discusses the importance of hypoxia in the formation of chronic low-grade inflammation in cancerous tumors. Finally, we discuss the effects of cycling hypoxia on the tumor microenvironment, in particular on the expression of VEGF-A, CCL2/MCP-1, CXCL1/GRO-α, CXCL8/IL-8, and COX-2 together with PGE2. These factors induce angiogenesis and recruit various cells into the tumor niche, including neutrophils and monocytes which, in the tumor, are transformed into tumor-associated neutrophils (TAN) and tumor-associated macrophages (TAM) that participate in tumorigenesis.


Assuntos
Fator 1 Induzível por Hipóxia/metabolismo , Hipóxia/metabolismo , Inflamação/metabolismo , NF-kappa B/metabolismo , Neoplasias/metabolismo , Biomarcadores , Suscetibilidade a Doenças , Ativação Enzimática , Humanos , Hipóxia/genética , Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Inflamação/etiologia , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Modelos Biológicos , Terapia de Alvo Molecular , Neoplasias/tratamento farmacológico , Neoplasias/etiologia , Neoplasias/patologia , Óxido Nítrico/metabolismo , Oxirredução , Espécies Reativas de Oxigênio/metabolismo , Microambiente Tumoral
13.
Molecules ; 26(14)2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34299460

RESUMO

Breast milk has the most suitable composition for the proper development in the first year of a child's life. However, it is often replaced with artificial milk. The aim of the study was to analyze the composition of essential elements: Na, K, Ca, P, Mg, Fe, Zn, Cu, and Mn as well as toxic elements: Ni, Pb, Sr, Li, and In in 18 formulas available in Poland. The daily supply was also estimated. The study was performed by Inductively Coupled Plasma Optical Emission Spectrometry method. The results showed the presence of all essential elements tested, but the content of P and Mn significantly differed from the concentrations declared. Such discrepancies can have significant impact on the daily dose of the bioelements taken. However, the content of elements was within the reference standards established by the EU Directive with exception of P, the amount of which exceeded the norms 5.23-18.80-times. Daily supply of P in tested milk as well as Fe and Mn provided with first and hypoallergenic formula exceeded the adequate intake. Analysis revealed the contamination with harmful elements-Pb, Sr, Li, and In were detected in almost all products. The study confirms the data concerning some discrepancies in composition and the contamination of food and may provide information on the feeding quality of children and estimation of health risk associated with exposure to toxic elements.


Assuntos
Fórmulas Infantis/análise , Fórmulas Infantis/química , Leite Humano/química , Humanos , Lactente , Fórmulas Infantis/toxicidade , Recém-Nascido , Micronutrientes/análise , Micronutrientes/química , Polônia , Oligoelementos/análise
14.
Biomolecules ; 11(5)2021 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-33919152

RESUMO

Exposure to low temperatures can be considered a stressor, which when applied for a specific time can lead to adaptive reactions. In our study we hypothesized that cold, when applied to the entire body, may be a factor that positively modifies the aging process of bones by improving the mechanisms related to the body's mineral balance. Taking the above into account, the aim of the study was to determine the concentration of calcium (Ca), magnesium (Mg), and phosphorus (P) in bones, and to examine bone density and concentrations of the key hormones for bone metabolism, namely parathyroid hormone (PTH), somatotropin (GH), 1,25-dihydroxyvitamin D3, 17-ß estradiol, testosterone (T) in plasma, and prostaglandin E2 (PGE2) in the bone of aging rats subjected to physical training in cold water. The animals in the experiment were subjected to a series of swimming sessions for nine weeks. Study group animals (male and female respectively) performed swimming training in cold water at 5 ± 2 °C and in water with thermal comfort temperature (36 ± 2 °C). Control animals were kept in a sedentary condition. Immersion in cold water affects bone mineral metabolism in aging rats by changing the concentration of Ca, Mg, and P in the bone, altering bone mineral density and the concentration of key hormones involved in the regulation of bone mineral metabolism. The effect of cold-water immersion may be gender-dependent. In females, it decreases Ca and Mg content in bones while increasing bone density and 17-ß estradiol and 1,25-dihydroxyvitamin D3 levels, and with a longer perspective in aging animals may be positive not only for bone health but also other estrogen-dependent tissues. In males, cold water swimming decreased PTH and PGE2 which resulted in a decrease in phosphorus content in bones (with no effect on bone density), an increase in 1,25-dihydroxyvitamin D3, and increase in T and GH, and may have positive consequences especially in bones and muscle tissue for the prevention of elderly sarcopenia.


Assuntos
Envelhecimento/fisiologia , Crioterapia/métodos , Esforço Físico/fisiologia , Animais , Densidade Óssea/efeitos dos fármacos , Osso e Ossos/química , Calcitriol/análise , Calcitriol/sangue , Cálcio/análise , Temperatura Baixa , Dinoprostona/análise , Estradiol/análise , Estradiol/sangue , Feminino , Hormônio do Crescimento/análise , Hormônio do Crescimento/sangue , Magnésio/análise , Masculino , Hormônio Paratireóideo/análise , Hormônio Paratireóideo/sangue , Fósforo/análise , Condicionamento Físico Animal/métodos , Plasma/química , Ratos , Ratos Wistar , Testosterona/análise , Testosterona/sangue
15.
Int J Mol Sci ; 22(6)2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33802080

RESUMO

Recent studies on cyclin-dependent kinase (CDK) inhibitors have revealed that small molecule drugs have become very attractive for the treatment of cancer and neurodegenerative disorders. Most CDK inhibitors have been developed to target the ATP binding pocket. However, CDK kinases possess a very similar catalytic domain and three-dimensional structure. These features make it difficult to achieve required selectivity. Therefore, inhibitors which bind outside the ATP binding site present a great interest in the biomedical field, both from the fundamental point of view and for the wide range of their potential applications. This review tries to explain whether the ATP competitive inhibitors are still an option for future research, and highlights alternative approaches to discover more selective and potent small molecule inhibitors.


Assuntos
Quinases Ciclina-Dependentes , Proteínas de Neoplasias , Neoplasias , Doenças Neurodegenerativas , Inibidores de Proteínas Quinases , Sítios de Ligação , Quinases Ciclina-Dependentes/antagonistas & inibidores , Quinases Ciclina-Dependentes/química , Quinases Ciclina-Dependentes/metabolismo , Humanos , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/química , Proteínas de Neoplasias/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/enzimologia , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/enzimologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/uso terapêutico , Relação Estrutura-Atividade
16.
Int J Mol Sci ; 22(6)2021 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-33805800

RESUMO

Cyclin-dependent kinases (CDKs) are involved in many crucial processes, such as cell cycle and transcription, as well as communication, metabolism, and apoptosis. The kinases are organized in a pathway to ensure that, during cell division, each cell accurately replicates its DNA, and ensure its segregation equally between the two daughter cells. Deregulation of any of the stages of the cell cycle or transcription leads to apoptosis but, if uncorrected, can result in a series of diseases, such as cancer, neurodegenerative diseases (Alzheimer's or Parkinson's disease), and stroke. This review presents the current state of knowledge about the characteristics of cyclin-dependent kinases as potential pharmacological targets.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Ciclo Celular/genética , Quinases Ciclina-Dependentes/genética , Neoplasias/tratamento farmacológico , Doença de Parkinson/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Doença de Alzheimer/enzimologia , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Animais , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Apoptose/genética , Cardiomegalia/tratamento farmacológico , Cardiomegalia/enzimologia , Cardiomegalia/genética , Cardiomegalia/patologia , Fármacos Cardiovasculares/uso terapêutico , Ciclo Celular/efeitos dos fármacos , Quinases Ciclina-Dependentes/antagonistas & inibidores , Quinases Ciclina-Dependentes/metabolismo , Ciclinas/genética , Ciclinas/metabolismo , Regulação da Expressão Gênica , Humanos , Neoplasias/enzimologia , Neoplasias/genética , Neoplasias/patologia , Fármacos Neuroprotetores/uso terapêutico , Doença de Parkinson/enzimologia , Doença de Parkinson/genética , Doença de Parkinson/patologia , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/enzimologia , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/patologia
17.
Molecules ; 26(6)2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33807029

RESUMO

Natural products are gaining more interest recently, much of which focuses on those derived from medicinal plants. The common chicory (Cichorium intybus L.), of the Astraceae family, is a prime example of this trend. It has been proven to be a feasible source of biologically relevant elements (K, Fe, Ca), vitamins (A, B1, B2, C) as well as bioactive compounds (inulin, sesquiterpene lactones, coumarin derivatives, cichoric acid, phenolic acids), which exert potent pro-health effects on the human organism. It displays choleretic and digestion-promoting, as well as appetite-increasing, anti-inflammatory and antibacterial action, all owing to its varied phytochemical composition. Hence, chicory is used most often to treat gastrointestinal disorders. Chicory was among the plants with potential against SARS-CoV-2, too. To this and other ends, roots, herb, flowers and leaves are used. Apart from its phytochemical applications, chicory is also used in gastronomy as a coffee substitute, food or drink additive. The aim of this paper is to present, in the light of the recent literature, the chemical composition and properties of chicory.


Assuntos
Cichorium intybus/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Antiparasitários/química , Antiparasitários/farmacologia , Antivirais/química , Antivirais/farmacologia , Cichorium intybus/fisiologia , Culinária , Hipersensibilidade Alimentar/etiologia , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Plantas Medicinais/química , Tratamento Farmacológico da COVID-19
18.
Brain Sci ; 11(1)2021 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-33467126

RESUMO

Although glioblastoma multiforme (GBM) is a widely researched cancer of the central nervous system, we still do not know its full pathophysiological mechanism and we still lack effective treatment methods as the current combination of surgery, radiotherapy, and chemotherapy does not bring about satisfactory results. The median survival time for GBM patients is only about 15 months. In this paper, we present the epidemiology of central nervous system (CNS) tumors and review the epidemiological data on GBM regarding gender, age, weight, height, and tumor location. The data indicate the possible influence of some anthropometric factors on the occurrence of GBM, especially in those who are male, elderly, overweight, and/or are taller. However, this review of single and small-size epidemiological studies should not be treated as definitive due to differences in the survey methods used. Detailed epidemiological registers could help identify the main at-risk groups which could then be used as homogenous study groups in research worldwide. Such research, with less distortion from various factors, could help identify the pathomechanisms that lead to the development of GBM.

19.
Int J Mol Sci ; 22(2)2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33467722

RESUMO

Hypoxia is an integral component of the tumor microenvironment. Either as chronic or cycling hypoxia, it exerts a similar effect on cancer processes by activating hypoxia-inducible factor-1 (HIF-1) and nuclear factor (NF-κB), with cycling hypoxia showing a stronger proinflammatory influence. One of the systems affected by hypoxia is the CXC chemokine system. This paper reviews all available information on hypoxia-induced changes in the expression of all CXC chemokines (CXCL1, CXCL2, CXCL3, CXCL4, CXCL5, CXCL6, CXCL7, CXCL8 (IL-8), CXCL9, CXCL10, CXCL11, CXCL12 (SDF-1), CXCL13, CXCL14, CXCL15, CXCL16, CXCL17) as well as CXC chemokine receptors-CXCR1, CXCR2, CXCR3, CXCR4, CXCR5, CXCR6, CXCR7 and CXCR8. First, we present basic information on the effect of these chemoattractant cytokines on cancer processes. We then discuss the effect of hypoxia-induced changes on CXC chemokine expression on the angiogenesis, lymphangiogenesis and recruitment of various cells to the tumor niche, including myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), regulatory T cells (Tregs) and tumor-infiltrating lymphocytes (TILs). Finally, the review summarizes data on the use of drugs targeting the CXC chemokine system in cancer therapies.


Assuntos
Quimiocinas CXC/metabolismo , Regulação Neoplásica da Expressão Gênica , Hipóxia , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Receptores CXCR/metabolismo , Fatores Quimiotáticos/metabolismo , Citocinas/metabolismo , Células Endoteliais/metabolismo , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Inflamação , Microcirculação , Subunidade p50 de NF-kappa B/metabolismo
20.
Biol Trace Elem Res ; 199(3): 955-967, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32557104

RESUMO

In this study, we investigated the ability of THP-1 monocytes and macrophages to accumulate lead (Pb) in vitro, relative to Pb concentration and length of exposure. Moreover, we also evaluated the effect of Pb accumulation on cell viability and apoptosis. THP-1 monocytes and macrophages were cultured in the presence of Pb at 1.25 µg/dL, 2.5 µg/dL, 5 µg/dL, and 10 µg/dL. Pb accumulation was examined by inductively coupled plasma and confocal microscopy. The influence of Pb on cell viability, apoptosis, and necrosis was assessed using flow cytometry. The results showed that Pb was toxic to THP-1 monocytes/macrophages even at very low environmental concentrations. Despite the use of low concentrations, both monocytes and macrophages showed dose-dependent and time-dependent decreases in viability, with a simultaneous increase in the percentage of early and late apoptotic cells. Macrophages reacted more strongly to Pb than monocytes. When exposed to the same Pb concentrations, they showed lower viability and a higher percentage of necrotic cells. The incubation time positively correlated with Pb accumulation in a dose-dependent manner. The obtained results indicate that environmental exposure to low Pb concentrations may significantly impair the function of macrophages, with the increased number of apoptotic cells potentially contributing to the development of many pathologies in the brain and whole body.


Assuntos
Chumbo , Monócitos , Apoptose , Sobrevivência Celular , Humanos , Chumbo/toxicidade , Macrófagos
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