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1.
Nucleic Acids Res ; 52(D1): D1210-D1217, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38183204

RESUMO

The Catalogue Of Somatic Mutations In Cancer (COSMIC), https://cancer.sanger.ac.uk/cosmic, is an expert-curated knowledgebase providing data on somatic variants in cancer, supported by a comprehensive suite of tools for interpreting genomic data, discerning the impact of somatic alterations on disease, and facilitating translational research. The catalogue is accessed and used by thousands of cancer researchers and clinicians daily, allowing them to quickly access information from an immense pool of data curated from over 29 thousand scientific publications and large studies. Within the last 4 years, COSMIC has substantially expanded its utility by adding new resources: the Mutational Signatures catalogue, the Cancer Mutation Census, and Actionability. To improve data accessibility and interoperability, somatic variants have received stable genomic identifiers that are associated with their genomic coordinates in GRCh37 and GRCh38, and new export files with reduced data redundancy have been made available for download.


Assuntos
Bases de Dados Genéticas , Genômica , Neoplasias , Humanos , Bases de Dados Factuais , Bases de Conhecimento , Mutação , Neoplasias/genética , Bases de Dados Genéticas/tendências , Internet
2.
PLoS Biol ; 22(1): e3002477, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38271296

RESUMO

Curated scientific databases catalogue and amplify research findings to maximize their reach. Authors should write their papers with this in mind, ensuring that data are accurate, easy to extract, and presented in standardized formats.


Assuntos
Redação , Bases de Dados Factuais
3.
Plant Foods Hum Nutr ; 79(1): 151-158, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38231454

RESUMO

Amaranth, quinoa, and buckwheat are the representatives of pseudocereals, different parts and by-products of which are used in daily nutrition and food processing industry. However, only scarce information exists on the bioactivity of their oils. Thus, oils obtained from amaranth, buckwheat, and red, yellow, and white quinoa seeds were evaluated in terms of their nutritional (fatty acid profile, squalene), cytotoxic (against normal and neoplastic gastrointestinal, prostate, and skin cells), anti-inflammatory and antiradical (interleukin 6, TNF-alpha, nitric oxide, DPPH, Total phenolics, and superoxide dismutase) potential in the in vitro model. Linoleic (42.9-52.5%) and oleic (22.5-31.1%) acids were the two main unsaturated, while palmitic acid (4.9-18.6%) was the major saturated fatty acid in all evaluated oils. Squalene was identified in all evaluated oils with the highest content in amaranth oil (7.6 g/100 g), and the lowest in buckwheat oil (2.1 g/100 g). The evaluated oils exerted a high direct cytotoxic impact on cancer cells of different origins, but also revealed anti-inflammatory and antiradical potentials. Yellow quinoa oil was the most active, especially toward skin (A375; IC50 6.3 µg/mL), gastrointestinal (HT29 IC50 4.9 µg/mL), and prostate cancer cells (LNCaP IC50 7.6 µg/mL). The observed differences in the activity between the oils from the tested quinoa varieties deserve further studies. High selectivity of the oils was noted, which indicates their safety to normal cells. The obtained results indicate that the oils are good candidates for functional foods with perspective chemopreventive potential.


Assuntos
Sementes , Esqualeno , Esqualeno/análise , Espectroscopia de Infravermelho com Transformada de Fourier , Sementes/química , Ácidos Graxos/análise , Óleos de Plantas/análise , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/análise
4.
J Pharm Biomed Anal ; 241: 115982, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38237542

RESUMO

In recent years, there has been a growing interest in the therapeutic potential of natural compounds, particularly of plant origin, owing to their demonstrated anti-inflammatory properties. Among these, Anacardium occidentale, commonly known as cashew, has garnered significant attention due to its reputed health benefits. This study aim to establish a correlation between the bioactive compounds contained in the extracts of Anacardium occidentale and its anti-inflammatory activity. Dried Anacardium occidentale leaves powder was used as the extraction matrix. Extraction techniques are maceration, pressurized fluid extraction (PFE), and supercritical fluid extraction (SFE). The preliminary analysis of extracts was made by LC-MS/MS. The Response Surface Methodology (RSM), Principal Component Analysis (PCA), and heat maps were employed to model the influence of experimental conditions on extraction yield and peak area of specific compounds from the plant. To evaluate anti-inflammatory activity, RAW 264.7 cells were cultured, activated with LPS, and treated with varying concentrations of the plant extracts. Cell proliferation was assessed using the XTT assay. Indeed, Anacardium occidentale extracts contain anacardic acids, cardanols, and cardol, with distinct profiles yielded by SFE and ethanol-based methods. RSM shows that temperature and ethanol, as additives to CO2, significantly affect extraction efficiency in both PFE and SFE. Moreover, this composition with SFE demonstrate higher selectivity for specific group of compounds. The extracts exhibit anti-inflammatory properties without cytotoxicity in macrophages, reducing levels of pro-inflammatory proteins COX-2, COX-1, and TLR4 in activated cells. This suggests their potential as anti-inflammatory agents without adverse effects on cell viability or pro-inflammatory protein levels in non-activated cells. Overall, these findings underscore the promising therapeutic potential of Anacardium occidentale extracts in mitigating inflammation, while also providing crucial insights into optimizing the extraction process for targeted compound isolation. Thus, this makes a good prospect for the development of anti-inflammatory drugs from this plant.


Assuntos
Alcaloides , Anacardium , Dióxido de Carbono , Cromatografia Líquida , Espectrometria de Massas em Tandem , Anti-Inflamatórios/farmacologia , Extratos Vegetais/farmacologia , Etanol
5.
Pharmaceuticals (Basel) ; 16(2)2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-37259305

RESUMO

It is estimated that in patients taking antipsychotic drugs (APDs), metabolic syndrome occurs 2-3 times more often than in the general population. It manifests itself in abdominal obesity, elevated glucose concentration, and dyslipidemia. Despite the high prevalence of this disorder, only a small percentage of patients receive appropriate and effective treatment, and none of the available methods for preventing or treating APD-induced metabolic side effects is satisfactory. A promising supplement to antipsychotic therapy appears to be ligands of the serotonin 6 (5-HT6) receptor. The present study aimed to examine the chronic effects of the selected APDs (haloperidol, risperidone, olanzapine), administered alone and in combination with a selective 5-HT6 agonist (WAY-181187) or antagonist (SB-742457), on weight gain, food intake, serum lipid profile, glucose level, and a spectrum of hormones derived from adipose (leptin, adiponectin) and gastrointestinal (insulin, ghrelin) tissue in rats. SB-742457 inhibited increased weight gain and alleviated hyperglycemia induced by APDs more strongly than did WAY-181187, but also intensified dyslipidemia. WAY-181187 tended to improve the lipid profile, but increased the glucose level. The greatest benefits were obtained when WAY-181187 or SB-742457 were co-administered with haloperidol. It is difficult to assess whether the modification of the serum levels of insulin, leptin, ghrelin, and adiponectin depended on the treatment applied or other drug-independent factors; therefore, further research is needed.

6.
Int J Mol Sci ; 23(19)2022 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-36232749

RESUMO

This study aimed to extend the body of preclinical research on prototype dual-acting compounds combining the pharmacophores relevant for inhibiting cyclic nucleotide phosphodiesterase 10 (PDE10A) and serotonin 5-HT1A/5-HT7 receptor (5-HT1AR/5-HT7R) activity into a single chemical entity (compounds PQA-AZ4 and PQA-AZ6). After i.v. administration of PQA-AZ4 and PQA-AZ6 to rats, the brain to plasma ratio was 0.9 and 8.60, respectively. After i.g. administration, the brain to plasma ratio was 5.7 and 5.3, respectively. An antidepressant-like effect was observed for PQA-AZ6 in the forced swim test, after chronic 21-day treatment via i.p. administration with 1 mg/kg/day. Both compounds revealed an increased level of brain-derived neurotrophic factor (Bdnf) mRNA in the hippocampus and prefrontal cortex. Moreover, PQA-AZ4 and PQA-AZ6 completely reversed (+)-MK801-induced memory disturbances comparable with the potent PDE10 inhibitor, compound PQ-10. In the safety profile that included measurements of plasma glucose, triglyceride, and total cholesterol concentration, liver enzyme activity, the total antioxidant activity of serum, together with weight gain, compounds exhibited no significant activity. However, the studied compounds had different effects on human normal fibroblast cells as revealed in in vitro assay. The pharmacokinetic and biochemical results support the notion that these novel dual-acting compounds might offer a promising therapeutic tool in CNS-related disorders.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Demência , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Antioxidantes , Disponibilidade Biológica , Glicemia , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Colesterol , Maleato de Dizocilpina , Humanos , Transtornos da Memória/tratamento farmacológico , Nucleotídeos Cíclicos , Diester Fosfórico Hidrolases , RNA Mensageiro , Ratos , Serotonina/metabolismo , Triglicerídeos
7.
Arch Pharm (Weinheim) ; 355(7): e2100423, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35396875

RESUMO

The present study aimed to design and synthesize a series of 2-hydroxy-3-(4-aryl-1-piperazinyl)propyl phthalimide derivatives, which are analogs of 1H-pyrrolo[3,4-c]pyridine-1,3(2H)-dione derivatives with proven analgesic effect. In accordance with the basic principle proposed by Lipinski's rule, the probable bioavailabilities of the F1-F4 phthalimides were assessed. The obtained values indicate good absorption after oral administration and the ability to cross the blood-brain barrier. The four compounds F1-F4 differing in the type of pharmacophore in the phenyl group of the 2-hydroxy-3-(4-aryl-1-piperazinyl)propyl on the imide nitrogen atom (R, F1-F3) and the 4-benzhydryl analog (F4) were selected for in vitro and in vivo studies. Based on the in vitro studies, the effects of compounds F1-F4 on cell viability/proliferation and COX-2 levels were evaluated. Moreover, using in vivo methods, the compounds were tested for antinociceptive activity in models of acute pain (the writhing and the hot-plate tests) in mice. Their influence on the motor coordination effect and locomotor activity was also tested. The obtained results revealed that the compounds F1-F4 strongly suppress the pain of peripheral origin and to a lesser extent (F1-F3) pain of central/supraspinal origin. In the in vitro studies, F1-F4 reduced the COX-2 level in lipopolysaccharide-activated RAW 264.7 cells, which suggests their anti-inflammatory activity.


Assuntos
Analgésicos , Dor , Animais , Ciclo-Oxigenase 2 , Camundongos , Dor/tratamento farmacológico , Medição da Dor , Relação Estrutura-Atividade
8.
Life Sci ; 293: 120345, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35065163

RESUMO

Endothelial cells are characterized by intense metabolic activity and control of homeostasis. Exposure to benzo(a)pyrene (BaP) plays an important role in the etiology of atherosclerosis. The study aimed to determine the effect of arachidonic (ARA), and eicosapentaenoic acid (EPA) on pro-inflammatory gene and protein levels in human umbilical vein endothelial cells (HUVEC) exposed to BaP. Cyclooxygenase-2 (COX-2), aryl hydrocarbon receptor (AHR), and glutathione S transferase Mu1 (GSTM1) proteins expression were analyzed by Western blot. Prostaglandin synthase 2 (PTGS2), AHR, GSTM1, phospholipase A2 (PLA2G4A), cytochrome P450 CYP1A1, intercellular adhesion molecule-1 (ICAM-1), endothelial nitric-oxide synthase (NOS3), and vascular adhesion molecule-1 gene expression (VCAM-1) was analyzed in Real time-qPCR. Phospholipase A2 activity was measured using the ELISA technique, and CYP1A1 activity was analyzed in luminescence assay. The highest amount of COX-2, the most increased activity of CYP1A1 and cPLA2, and overexpression of GSTM1, CYP1A1, ICAM-1, and VCAM-1 gene was observed in HUVEC cells treated with BaP. After co-treatment with BaP and ARA or EPA, an increase of GSTM1 level was observed. Incubation of endothelial cells with ARA or EPA and BaP resulted in lower CYP1A1 and cPLA2 activities and lower expression of VCAM-1 and ICAM-1 genes. Significant overexpression of AHR, GSTM1, CYP1A1, PTGS2, PLA2G4A, and NOS3 genes was noted in cells treated with EPA and BaP. Our data suggest a beneficial effect of EPA and ARA on endothelial function. Thus, it justifies further research on the participation of fatty acids in the regulation of physiological and pathological processes in endothelial cells.


Assuntos
Ácido Araquidônico/farmacologia , Benzo(a)pireno/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Ácido Eicosapentaenoico/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Sobrevivência Celular/fisiologia , Citocromo P-450 CYP1A1/metabolismo , Relação Dose-Resposta a Droga , Humanos
9.
Life (Basel) ; 11(9)2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34575127

RESUMO

The beneficial effect of n-3 fatty acids can be related to anti-inflammatory properties. The aim of the study was to analyzed the effect of eicosapentaenoic acid (EPA) on 3T3-L1 cells (murine embryonic fibroblasts‒preadipocytes) activated with inflammatory factors (IF). Cells were incubated with 50 µmol of EPA for 48 h, and then activated with lipopolysaccharide (LPS) or tumor necrosis factor-α (TNF-α). The level of cycloxygenase-2 (Prostaglandin-Endoperoxide Synthase 2, PTGS2, COX-2), cytosolic prostaglandin synthase E2 (cPGES), fatty acid binding protein 4 (FABP4), toll-like receptor 4 (TLR4), glucose receptor type 4 (GLUT-4), and cannabinoid receptor 2 (CB2) was determined using Western blot analysis. The phospholipase A2 (Pla2g4a), and prostaglandin-Endoperoxide Synthase 2 (Ptgs2) gene expression was analyzed by real-time qPCR. After EPA and IF activation, a significant decrease in the COX-2, cPGES, and TRL4 protein levels was observed. Incubation of cells with EPA and IF resulted in a decrease in Ptgs2 and an increase in the Pla2g4a gene. A significant increase in the CB2 protein was observed in adipocytes co-treated with EPA and IF. The results indicated an anti-inflammatory properties of EPA. Interestingly, the activation of the GLUT4 receptor by EPA suggests an unique role of this FA in the regulation of the adipocyte metabolism and prevention of insulin resistance.

10.
Pharmaceuticals (Basel) ; 14(9)2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34577645

RESUMO

Usnic acid (UA) is a chiral lichen metabolite with an interesting pharmacological profile. The aim of this study was to compare the anti-melanoma effect of (+)-UA and (-)-UA in an in vitro model by studying their impact on the cells as well as the processes associated with cancer progression. The effect of UA enantiomers on the viability, proliferation, and invasive potential of three melanoma cell lines (HTB140, A375, WM793) was evaluated. Their interaction with a chemotherapeutic drug-doxorubicin was assessed by isobolographic analysis. Anti-inflammatory and anti-tyrosinase properties of (+)-UA and (-)-UA were also examined. Both UA enantiomers dose- and time-dependently decreased the viability of all three melanoma cell lines. Their synergistic effect with doxorubicin was observed on A375 cells. (+)-Usnic acid at a sub-cytotoxic dose strongly inhibited melanoma cells migration. Both UA enantiomers decreased the release of pro-inflammatory mediators. The cytotoxic effect of (+)-UA and (-)-UA depends greatly on the melanoma cell type; however, the overall anti-melanoma potential is perspective. Our results indicate that the strategy of combining usnic acid enantiomers with cytostatic drugs may be an interesting option to consider in combating melanoma; however, further studies are required.

11.
Front Pharmacol ; 12: 691598, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34276379

RESUMO

Posttraumatic stress disorder (PTSD) has been associated with abnormal regulation of the hypothalamic-pituitary-adrenal gland axis (HPA). Women demonstrate a more robust HPA response and are twice as likely to develop PTSD than men. The role of sex hormones in PTSD remains unclear. We investigated whether post-trauma chronic treatment with the GABA-ergic agent tiagabine and dopamine-mimetic pramipexole affected the behavioral outcome and plasma levels of corticosterone, testosterone, or 17ß-estradiol in female and male mice. These medications were investigated due to their potential capacity to restore GABA-ergic and dopaminergic deficits in PTSD. Animals were exposed to a single prolonged stress procedure (mSPS). Following 13 days treatment with tiagabine (10 mg/kg) or pramipexole (1 mg/kg) once daily, the PTSD-like phenotype was examined in the fear conditioning paradigm. Plasma hormones were measured almost immediately following the conditioned fear assessment. We report that the exposure to mSPS equally enhanced conditioned fear in both sexes. However, while males demonstrated decreased plasma corticosterone, its increase was observed in females. Trauma elevated plasma testosterone in both sexes, but it had no significant effects on 17ß-estradiol. Behavioral manifestation of trauma was reduced by pramipexole in both sexes and by tiagabine in females only. While neither compound affected corticosterone in stressed animals, testosterone levels were further enhanced by tiagabine in females. This study shows sex-dependent efficacy of tiagabine but not pramipexole in a mouse model of PTSD-like symptoms and a failure of steroid hormones' levels to predict PTSD treatment efficacy.

12.
Neuropsychiatr Dis Treat ; 17: 2105-2127, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34211274

RESUMO

BACKGROUND: The presence of depressive and anxiety symptoms in patients with schizophrenia may have an important impact on treatment and compliance. Hence, interventions addressing such comorbidity in schizophrenia should be explored. One target may be a serotonergic 5-HT6 receptor (5-HT6R) since its ligands displayed antidepressant- and anxiolytic-like activities in preclinical experiments. METHODS: Acute and chronic (21 days) administration of haloperidol or risperidone in combination with a selective 5-HT6R agonist (WAY-181187) or antagonist (SB-742457) to rats was performed for detecting antidepressant- and anxiolytic-like behaviors. In addition, the level of brain-derived neurotrophic factor (BDNF) protein and its gene expression in hippocampus and prefrontal cortex were determined. RESULTS: Both single and chronic administration of WAY-181187 with haloperidol produced antidepressant- and anxiolytic-like activities. SB-742457 did not provide full benefits in terms of improvement of haloperidol-induced adverse mood effects. However, the administration of SB-742457 with risperidone triggered its anxiolytic-like activity. Both 5-HT6R ligands evoked no changes in haloperidol-induced effects on BDNF level. WAY-181187 induced repression of the BDNF gene while SB-742457 increased its expression in both structures. 5-HT6R ligands, when combined with risperidone, did not change BDNF protein level and increased gene expression in the hippocampus, while they elevated BDNF level and potentiated gene expression in the prefrontal cortex. CONCLUSION: The combined administration of WAY-181187 and haloperidol provided the greatest benefits, which were manifested by antidepressant-like effects and suppression of the anxiogenic-like properties. The combined administration of risperidone with both agonist and antagonist resulted only in an anxiolytic-like effect. It seems that the anxiolytic-like effects induced by haloperidol or risperidone with the addition of 5-HT6R ligands are task-specific. The data on BDNF protein and gene expression did not fully correspond with the behavioral outcomes, and thus it appears that other factors/mechanisms are involved in the observed antidepressant- and/or anxiolytic-like effects.

13.
Biochemistry (Mosc) ; 86(5): 525-532, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33993857

RESUMO

Fatty acids (FAs) present in the adipose tissue (AT) can be modified by elongases and desaturases. These enzymes are regulated by different factors including nutrients. The aim of the study was to evaluate the impact of high-sucrose diet (HSD; 68% sucrose) on the levels of mRNAs for elongases (Elovl2, Elovl5, Elovl6) and desaturases (Fads1, Fads2, Scd) and on the activity of the corresponding proteins in the rat AT. Male Wistar rats were randomized into two study groups: fed with an HSD and with a standard diet (ST). The mRNA levels were determined by a semi-quantitative reverse transcription-PCR. FA composition was analyzed by gas chromatography, and FA ratios were used to estimate the activity of the enzymes. In the HSD rats, the levels of Elovl5, Elovl6, Fads1, and Scd mRNAs were higher, while the level of Fads2 mRNA was lower than in the ST group. Higher levels of Elovl5 and Elovl6 mRNAs corresponded to higher relative activities of these enzymes, while downregulation of the Fads2 mRNA was associated with the lower activity of this desaturase. In contrast, an increase in the level of Scd mRNA was accompanied by a decrease in the enzyme activity. Less monounsaturated FAs were detected in the AT of HSD rats than in the ST group. The composition of individual FAs differed between the groups. This study supports the notion that the regulation of mRNA levels and activity of both elongases and desaturases play an important role in managing the AT lipid composition in response to changes in the dietary status.


Assuntos
Tecido Adiposo/enzimologia , Sacarose na Dieta/farmacologia , Ácidos Graxos Dessaturases/genética , Elongases de Ácidos Graxos/genética , Ácidos Graxos/metabolismo , Tecido Adiposo/metabolismo , Animais , Dieta , Sacarose na Dieta/metabolismo , Ácidos Graxos Dessaturases/metabolismo , Elongases de Ácidos Graxos/metabolismo , Ácidos Graxos/análise , Regulação da Expressão Gênica , Masculino , RNA Mensageiro , Ratos , Ratos Wistar
14.
Plant Foods Hum Nutr ; 76(1): 76-82, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33492585

RESUMO

Kohlrabi sprouts are just gaining popularity as the new example of functional food. The study was focused on the influence of germination time and light conditions on glucosinolates, phenolic acids, flavonoids, and fatty acids content in kohlrabi sprouts, in comparison to the bulbs. The effect of kohlrabi products on SW480, HepG2 and BJ cells was also determined. The length of sprouting time and light availability significantly influenced the concentrations of the phenolic compounds. Significant differences in progoitrin concentrations were observed between the sprouts harvested in light and in the darkness, with significantly lower content for darkness conditions. Erucic acid was the dominant fatty acid found in sprouts (14.5-34.5%). Sprouts and bulbs were less toxic to normal than to cancer cells. The sprouts stimulated necrosis (56.4%) more than apoptosis (34.1%) in SW480 cells, while the latter effect was predominant for the bulbs. Both sprouts and bulbs caused rather necrosis (45.5 and 63.9%) than apoptosis (32 and 32.5%) in HepG2 cells.


Assuntos
Alimento Funcional , Germinação , Flavonoides , Fenóis/análise , Raízes de Plantas/química
15.
Nucleic Acids Res ; 49(D1): D192-D200, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33211869

RESUMO

Rfam is a database of RNA families where each of the 3444 families is represented by a multiple sequence alignment of known RNA sequences and a covariance model that can be used to search for additional members of the family. Recent developments have involved expert collaborations to improve the quality and coverage of Rfam data, focusing on microRNAs, viral and bacterial RNAs. We have completed the first phase of synchronising microRNA families in Rfam and miRBase, creating 356 new Rfam families and updating 40. We established a procedure for comprehensive annotation of viral RNA families starting with Flavivirus and Coronaviridae RNAs. We have also increased the coverage of bacterial and metagenome-based RNA families from the ZWD database. These developments have enabled a significant growth of the database, with the addition of 759 new families in Rfam 14. To facilitate further community contribution to Rfam, expert users are now able to build and submit new families using the newly developed Rfam Cloud family curation system. New Rfam website features include a new sequence similarity search powered by RNAcentral, as well as search and visualisation of families with pseudoknots. Rfam is freely available at https://rfam.org.


Assuntos
Bases de Dados de Ácidos Nucleicos , Metagenoma , MicroRNAs/genética , RNA Bacteriano/genética , RNA não Traduzido/genética , RNA Viral/genética , Bactérias/genética , Bactérias/metabolismo , Pareamento de Bases , Sequência de Bases , Humanos , Internet , MicroRNAs/classificação , MicroRNAs/metabolismo , Anotação de Sequência Molecular , Conformação de Ácido Nucleico , RNA Bacteriano/classificação , RNA Bacteriano/metabolismo , RNA não Traduzido/classificação , RNA não Traduzido/metabolismo , RNA Viral/classificação , RNA Viral/metabolismo , Alinhamento de Sequência , Análise de Sequência de RNA , Software , Vírus/genética , Vírus/metabolismo
16.
Nutrients ; 12(9)2020 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-32825449

RESUMO

Zinc (Zn) was found to enhance the antidepressant efficacy of imipramine (IMI) in human depression and animal tests/models of depression. However, the underlying mechanism for this effect remains unknown. We measured the effect of intragastric (p.o.) combined administration of IMI (60 mg/kg) and Zn (40 mg Zn/kg) in the forced swim test (FST) in mice. The effect of Zn + IMI on serum, brain, and intestinal Zn concentrations; Zn transporter (ZnT, ZIP) protein levels in the intestine and ZnT in the brain; including BDNF (brain-derived neurotrophic factor) and CREB (cAMP response element-binding protein) protein levels in the brain were evaluated. Finally, the effect of IMI on Zn permeability was measured in vitro in colon epithelial Caco-2 cells. The co-administration of IMI and Zn induced antidepressant-like activity in the FST in mice compared to controls and Zn or IMI given alone. This effect correlated with increased BDNF and the ratio of pCREB/CREB protein levels in the prefrontal cortex (PFC) compared to the control group. Zn + IMI co-treatment increased Zn concentrations in the serum and brain compared to the control group. However, in serum, co-administration of IMI and Zn decreased Zn concentration compared to Zn alone treatment. Also, there was a reduction in the Zn-induced enhancement of ZnT1 protein level in the small intestine. Zn + IMI also induced an increase in the ZnT4 protein level in the PFC compared to the control group and normalized the Zn-induced decrease in the ZnT1 protein level in the hippocampus (Hp). The in vitro studies revealed enhanced Zn permeability (observed as the increased transfer of Zn through the intestinal cell membrane) after IMI treatment. Our data indicate that IMI enhances Zn transfer through the intestinal tract and influences the redistribution of Zn between the blood and brain. These mechanisms might explain the enhanced antidepressant efficacy of combined IMI/Zn treatment observed in the FST in mice.


Assuntos
Antidepressivos Tricíclicos/farmacologia , Encéfalo/metabolismo , Imipramina/farmacologia , Zinco/metabolismo , Zinco/farmacologia , Administração Oral , Animais , Antidepressivos Tricíclicos/administração & dosagem , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Células CACO-2 , Proteínas de Transporte/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Sinergismo Farmacológico , Trato Gastrointestinal/metabolismo , Humanos , Imipramina/administração & dosagem , Masculino , Camundongos , Zinco/administração & dosagem , Zinco/sangue
17.
Chem Biodivers ; 17(9): e2000391, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32558141

RESUMO

Hypholoma lateritium is an edible macrofungus with a common distribution in Europe, North America, and the Far East. The aim of this study was to investigate the potential anti-inflammatory effects of H. lateritium extracts and its isolated steroids: fasciculic acid B, fasciculol E, fasciculol C, lanosta-7,9(11)-diene-12ß,21α-epoxy-2α,3ß,24ß,25-tetraol, fasciculol F, and demethylincisterol A2. Organic (hexane, chloroform and 50 % methanol) and water extracts of H. lateritium were subjected to in vitro assays to determine pro-inflammatory protein levels, such as cyclooxygenase-2 (COX-2), cytosolic prostaglandin E2 synthase (cPGES), and antioxidant nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Fungal extracts demonstrated significant activities on pro-inflammatory protein levels with minor differences among the activities of the fractions of different polarities. All the compounds proved to exert notable inhibitory properties on COX-2 and were capable to stimulate the Nrf2 pathway. Fungal extracts and the compounds exerted no cytotoxic activities on RAW 264.7 cells.


Assuntos
Agaricales/química , Anti-Inflamatórios/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Ciclo-Oxigenase 2/metabolismo , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Esteroides/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Inibidores de Ciclo-Oxigenase 2/química , Inibidores de Ciclo-Oxigenase 2/isolamento & purificação , Camundongos , Estrutura Molecular , Fator 2 Relacionado a NF-E2/metabolismo , Células RAW 264.7 , Esteroides/química , Esteroides/isolamento & purificação
19.
Biol Trace Elem Res ; 194(2): 603-613, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31256391

RESUMO

Lentinula edodes (shiitake), an edible and medicinal mushroom, was chosen for this study with the aim of evaluating the possibility of release of bioelements into artificial digestive juices and analyzing the anti-inflammatory properties. The extracts were prepared from fruiting bodies and biomass enriched with copper (Cu), zinc (Zn), and selenium (Se). The content of bioelements was analyzed by total reflection X-ray fluorescence method. Relatively low content of elements was observed in the fruiting bodies: Cu-1.6, Zn-7.6, and Se-0.12 mg/100 g d.w. compared to mycelial cultures. The anti-inflammatory properties were evaluated in RAW 264.7 cells. Based on the levels of cyclooxygenase 2 protein, nuclear factor erythroid 2-related factor 2, and peroxisome proliferator-activated receptor γ determined using Western blot technique, it was found that the addition of bioelements enhanced the anti-inflammatory properties of mycelium. This indicates that L. edodes cultured on a suitable medium may be used as a potential component of anti-inflammatory products.


Assuntos
Selênio , Cogumelos Shiitake , Anti-Inflamatórios/farmacologia , Digestão , Micélio , Selênio/farmacologia
20.
Eur J Gastroenterol Hepatol ; 32(3): 318-324, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31714390

RESUMO

OBJECTIVES: Clostridium difficile infection (CDI) is an acute gastrointestinal infection caused by anaerobic, toxin-producing bacteria. During the course of CDI, there is a general inflammatory state. In order to gain a deeper understanding of the role of fatty acids (FAs) in the pathogenesis of acute infection we analyzed their plasma content in both patients with CDI and controls. METHODS: The study groups included 40 patients with CDI and 40 healthy volunteers. Plasma FA content was analyzed by gas chromatography, resolvin D1 (RvD1) level using ELISA assay, and we assessed the white blood cell (WBC) count, neutrophil count and C-reactive protein (CRP) level. RESULTS: Patients with CDI were characterized by significantly higher values of WBC, neutrophils, platelets and CRP compared with the control group. The saturated FA index was statistically higher and total n-3 FA was significantly decreased in the plasma of CDI patients as compared with the control group. RvD1 content was significantly higher in the control group as compared with patients with CDI. CONCLUSION: In patients with good outcomes, we probably observed the effective resolution of inflammation, as reflected in n-3 FA metabolism and their significant decrease in plasma. This may indicate the therapeutic role of n-3 FA in CDI infection.


Assuntos
Clostridioides difficile , Infecções por Clostridium , Enterocolite Pseudomembranosa , Ácidos Docosa-Hexaenoicos , Ácidos Graxos , Humanos
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