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1.
Int J Mol Sci ; 25(8)2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38673738

RESUMO

The high content of bioactive compounds in Aronia melanocarpa fruit offers health benefits. In this study, the anti-atherosclerotic effect of Aronia extracts was assessed. The impact on the level of adhesion molecules and the inflammatory response of human umbilical vein endothelial cells (HUVECs) was shown in relation to the chemical composition and the stage of ripening of the fruits. Samples were collected between May (green, unripe) and October (red, overripe) on two farms in Poland, which differed in climate. The content of chlorogenic acids, anthocyanins, and carbohydrates in the extracts was determined using HPLC-DAD/RI. The surface expression of ICAM-1 and VCAM-1 in HUVECs was determined by flow cytometry. The mRNA levels of VCAM-1, ICAM-1, IL-6, and MCP-1 were assessed using the quantitative real-time PCR method. The farms' geographical location was associated with the quantity of active compounds in berries and their anti-atherosclerotic properties. Confirmed activity for green fruits was linked to their high chlorogenic acid content.


Assuntos
Aterosclerose , Frutas , Células Endoteliais da Veia Umbilical Humana , Photinia , Extratos Vegetais , Photinia/química , Humanos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Frutas/química , Aterosclerose/tratamento farmacológico , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Molécula 1 de Adesão Intercelular/genética , Antocianinas/farmacologia , Antocianinas/química , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Ácido Clorogênico/farmacologia , Ácido Clorogênico/química , Interleucina-6/metabolismo , Interleucina-6/genética
2.
Curr Issues Mol Biol ; 46(3): 2166-2180, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38534756

RESUMO

The purpose of this study was to evaluate the effect of genistein in nano, micro, and macro forms on the intensity of the DMBA-induced tumor process in rats and to understand the mechanisms of this action. The effect of genistein supplementation on the content of selected eicosanoids (HETEs, HODE, and HEPE) in the serum of rats was evaluated. The levels and expression of genes encoding various pro-inflammatory cytokines (IL-1, IL-6) and MMP-9 in the blood of rats were also investigated. The biological material for the study was blood obtained from female rats of the Sprague Dawley strain (n = 32). The animals were randomly divided into four groups: animals without supplementation, and animals supplemented at a dose of 0.2 mg/kg b.w. (0.1 mg/mL) with macro, micro (587 ± 83 nm), or nano (92 ± 41 nm) genistein. To induce mammary neoplasia (adenocarcinoma), rats were given 7,12-dimethyl-1,2-benz[a]anthracene (DMBA). The content of selected eicosanoids was determined by liquid chromatography with UV detection. An immunoenzymatic method was used to determine the content of cytokines and MMP-9. The expression of the IL-6, IL-1beta, and MMP-9 genes was determined with quantitative real-time PCR (qRT-PCR) using TaqMan probes. Based on the study, it was shown that supplementation of animals with genistein in macro, micro, and nano forms increased the intensity of the tumor process in rats. It was shown that the content of 12-HEPE, HODE, and 12-HETE in the serum of genistein-supplemented rats was statistically significantly lower with respect to the content of the aforementioned markers in the serum of rats receiving only a standard diet, devoid of supplementation. It was found that animals supplemented with nano-, micro-, and macrogenistein had higher levels of metalloproteinase-9, MMP-9, compared to animals without supplementation. There was a significant increase in MMP-9 gene expression in the blood of macrogenistein-supplemented animals, relative to the other groups of rats. On the basis of the study, it was shown that supplementation of animals with nano-, micro-, and macrogenistein had an effect on the development of the tumor process. Dietary supplementation with genistein significantly decreased the level of selected eicosanoids, which may have significant impacts on cancer development and progression.

3.
Curr Issues Mol Biol ; 46(2): 1413-1423, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38392209

RESUMO

According to the World Health Organization's statement, myocarditis is an inflammatory myocardium disease. Although an endometrial biopsy remains the diagnostic gold standard, it is an invasive procedure, and thus, cardiac magnetic resonance imaging has become more widely used and is called a non-invasive diagnostic gold standard. Myocarditis treatment is challenging, with primarily symptomatic therapies. An increasing number of studies are searching for novel diagnostic biomarkers and potential therapeutic targets. Microribonucleic acids (miRNAs) are small, non-coding RNA molecules that decrease gene expression by inhibiting the translation or promoting the degradation of complementary mRNAs. Their role in different fields of medicine has been recently extensively studied. This review discusses all relevant preclinical in vitro studies regarding microRNAs in myocarditis. We searched the PubMed database, and after excluding unsuitable studies and clinical and preclinical in vivo trials, we included and discussed 22 preclinical in vitro studies in this narrative review. Several microRNAs presented altered levels in myocarditis patients in comparison to healthy controls. Moreover, microRNAs influenced inflammation, cell apoptosis, and viral replication. Finally, microRNAs were also found to determine the level of myocardial damage. Further studies may show the vital role of microRNAs as novel therapeutic agents or diagnostic/prognostic biomarkers in myocarditis management.

4.
Biomedicines ; 11(12)2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38137372

RESUMO

The study of medicinal plants is important, as they are the natural reserve of potent biologically active compounds. With wide use in traditional medicine and the inclusion of several species (as parts and as a whole plant) in pharmacopeia, species from the genus Salvia L. are known for the broad spectrum of their biological activities. Studies suggest that these plants possess antioxidant, anti-inflammatory, antinociceptive, anticancer, antimicrobial, antidiabetic, antiangiogenic, hepatoprotective, cognitive and memory-enhancing effects. Phenolic acids, terpenoids and flavonoids are important phytochemicals, which are primarily responsible for the medicinal activity of Salvia L. This review collects and summarizes currently available data on the pharmacological properties of sage, outlining its principal physiologically active components, and it explores the molecular mechanism of their biological activity. Particular attention was given to the species commonly found in Kazakhstan, especially to Salvia trautvetteri Regel, which is native to this country.

5.
Biomedicines ; 11(10)2023 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-37893097

RESUMO

Myocarditis is an inflammatory heart disease with viruses as the most common cause. Regardless of multiple studies that have recently been conducted, the diagnostic options still need to be improved. Although endomyocardial biopsy is known as a diagnostic gold standard, it is invasive and, thus, only sometimes performed. Novel techniques of cardiac magnetic resonance are not readily available. Therapy in viral infections is based mainly on symptomatic treatment, while steroids and intravenous immunoglobulins are used in autoimmune myocarditis. The effectiveness of neither of these methods has been explicitly proven to date. Therefore, novel diagnostic and therapeutic strategies are highly needed. MiRNAs are small, non-coding molecules that regulate fundamental cell functions, including differentiation, metabolism, and apoptosis. They present altered levels in different diseases, including myocarditis. Numerous studies investigating the role of miRNAs in myocarditis have already been conducted. In this review, we discussed only the original preclinical in vivo research. We eventually included 30 studies relevant to the discussed area. The altered miRNA levels have been observed, including upregulation and downregulation of different miRNAs in the mice models of myocarditis. Furthermore, the administration of mimics or inhibitors of particular miRNAs was shown to significantly influence inflammation, morphology, and function of the heart and overall survival. Finally, some studies presented prospective advantages in vaccine development.

6.
Int J Mol Sci ; 24(17)2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37685901

RESUMO

Aortic stenosis (AS) is the most prevalent primary valve lesion demanding intervention. Two main treatment options are surgical aortic valve replacement or transcatheter aortic valve implantation. There is an unmet need for biomarkers that could predict treatment outcomes and become a helpful tool in guiding Heart Team in the decision-making process. Micro-ribonucleic acids (microRNAs/miRs) have emerged as potential biomarkers thoroughly studied in recent years. In this review, we aimed to summarize the current knowledge about the role of miRNAs in AS based on human subject research. Much research investigating miRNAs' role in AS has been conducted so far. We included 32 original human subject research relevant to the discussed field. Most of the presented miRNAs were studied only by a single research group. Nevertheless, several miRNAs appeared more than once, sometimes with high consistency between different studies but sometimes with apparent discrepancies. The molecular aspects of diseases are doubtlessly exciting and provide invaluable insights into the pathophysiology. Nevertheless, translating these findings, regarding biomarkers such as miRNAs, into clinical practice requires much effort, time, and further research with a focus on validating existing evidence.


Assuntos
Estenose da Valva Aórtica , MicroRNAs , Substituição da Valva Aórtica Transcateter , Humanos , MicroRNAs/genética , Estenose da Valva Aórtica/genética , Coração , Catéteres
7.
Biomedicines ; 11(8)2023 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-37626800

RESUMO

Research into early predictors of effective weight loss could help determine more effective therapeutic interventions. In this study, 106 subjects with class I obesity, genotyped with the fat mass and obesity-associated (FTO) rs9930506 gene variant, were enrolled into a 12-week weight loss program (WLP). Anthropometric and body composition measurements were controlled with bioelectrical impedance analysis (BIA) at baseline and after 4 and 12 weeks. Biopsies of abdominal subcutaneous adipose tissue (AT) and venous blood samples were collected to monitor changes in interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa B (NF-κB) mRNA levels in white blood cells (WBCs) and to assess if changes in WBC gene expression reflected changes in adipose tissue. The FTO rs9930506 variant had no effect on weight loss and no reduction in proinflammatory transcripts in WBCs or AT. Changes in anthropometric parameters were associated with changes in carbohydrate metabolism. A linear regression model showed that initial weight loss (after 4 weeks of the WLP) was the most predictive factor of weight loss success after 12 weeks of the WLP. Changes in plasma lipids or proinflammatory transcript levels in WBCs or AT were not associated with weight loss effectiveness. However, the gene expression in WBCs did reflect changes occurring in subcutaneous AT.

8.
J Clin Med ; 12(11)2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37298009

RESUMO

Background: Tinnitus severity is generally assessed by psychometric and audiological instruments. However, no objective measure exists to evaluate the subjective discomfort and suffering caused by this hearing phenomenon. The objective of this work was to determine the possible blood parameters for diagnostics and therapy. Methods: We measured tinnitus distress by using the Tinnitus Questionnaire (TQ) and collected tinnitus-related audiological measures, namely the hearing threshold (HT), tinnitus loudness (TL), and sensation level (SL, i.e., the tinnitus loudness/hearing threshold at a tinnitus frequency). Blood samples were taken from 200 outpatients of the Tinnitus Centre of the Charité, and 46 routine blood count parameters were examined. The possible interactions were determined by (robust) linear models. Results: Tinnitus distress and audiological measurements were largely uncorrelated but could partly be predicted by selected blood parameters. First, the erythrocyte counts predicted tinnitus distress to a small extent. Second, the levels of vitamin D3 explained about 6% of tinnitus loudness and, age-dependently, the hearing threshold variability. Last, the levels of uric acid explained about 5% of the sensation level variability. Conclusions: Tinnitus is a multidimensional phenomenon. The marginal influences of blood markers suggest the possible roles of inflammation and oxidative stress produced by psychological or somatic burdens. Clinically, a vitamin D substitution (in older patients) might have a hearing-protective effect.

9.
ACS Omega ; 8(21): 18663-18684, 2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-37273589

RESUMO

A novel series of N-acylated ciprofloxacin (CP) conjugates 1-21 were synthesized and screened as potential antimicrobial agents. Conjugates 1 and 2 were 1.25-10-fold more potent than CP toward all Staphylococci (minimal inhibitory concentration 0.05-0.4 µg/mL). Most of the chloro- (3-7), bromo- (8-11), and CF3-alkanoyl (14-16) derivatives expressed higher or comparable activity to CP against selected Gram-positive strains. A few CP analogues (5, 10, and 11) were also more effective toward the chosen clinical Gram-negative rods. Conjugates 5, 10, and 11 considerably influenced the phases of the bacterial growth cycle over 18 h. Additionally, compounds 2, 4-7, 9-12, and 21 exerted stronger tuberculostatic action against three Mycobacterium tuberculosis isolates than the first-line antitubercular drugs. Amides 1, 2, 5, 6, 10, and 11 targeted gyrase and topoisomerase IV at 2.7-10.0 µg/mL, which suggests a mechanism of antibacterial action related to CP. These findings were confirmed by molecular docking studies. In addition, compounds 3 and 15 showed high antiproliferative activities against prostate PC3 cells (IC50 2.02-4.8 µM), up to 6.5-2.75 stronger than cisplatin. They almost completely reduced the growth and proliferation rates in these cells, without a cytotoxic action against normal HaCaT cell lines. Furthermore, derivatives 3 and 21 induced apoptosis/necrosis in PC3 cells, probably by increasing the intracellular ROS amount, as well as they diminished the IL-6 level in tumor cells.

10.
Int J Mol Sci ; 25(1)2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38203363

RESUMO

Methylenetetrahydrofolate reductase (MTHFR) is a key regulatory enzyme in the one-carbon cycle. This enzyme is essential for the metabolism of methionine, folate, and RNA, as well as for the production of proteins, DNA, and RNA. MTHFR catalyses the irreversible conversion of 5,10-methylenetetrahydrofolate to its active form, 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine. Numerous variants of the MTHFR gene have been recognised, among which the C677T variant is the most extensively studied. The C677T polymorphism, which results in the conversion of valine to alanine at codon 222, is associated with reduced activity and an increased thermolability of the enzyme. Impaired MTHFR efficiency is associated with increased levels of homocysteine, which can contribute to increased production of reactive oxygen species and the development of oxidative stress. Homocysteine is acknowledged as an independent risk factor for cardiovascular disease, while chronic inflammation serves as the common underlying factor among these issues. Many studies have been conducted to determine whether there is an association between the C677T polymorphism and an increased risk of cardiovascular disease, hypertension, diabetes, and overweight/obesity. There is substantial evidence supporting this association, although several studies have concluded that the polymorphism cannot be reliably used for prediction. This review examines the latest research on MTHFR polymorphisms and their correlation with cardiovascular disease, obesity, and epigenetic regulation.


Assuntos
Doenças Cardiovasculares , Humanos , Doenças Cardiovasculares/genética , Epigênese Genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Metionina , Racemetionina , Homocisteína , Obesidade , RNA
11.
Biomedicines ; 10(12)2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36551896

RESUMO

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) is an enzyme responsible for producing an active form of folate. The MTHFR T677T genotype may have adverse health effects associated with weight gain and a reduction in folate availability. AIM: In this study, we examined the influence of the MTHFR C677T variant on BMI and determined its role as a risk factor for obesity. We also assessed the relationships between the MTHFR C677T genotype and folate and vitamin B12 concentrations in subjects before and after radical weight loss. METHODS: The study group consisted of 1712 Caucasian adults of Polish nationality with a wide range of body mass indexes (BMIs). DNA was extracted from the blood, and the C677T variant was tested with RFLP-PCR and real-time-PCR. RESULTS: There was no significant influence found for the MTHFR 677 TT genotype on BMI or the obesity risk in codominant, dominant or recessive inheritance models. Individuals with obesity and the TT genotype had significantly lower folate concentrations. After radical weight reduction, the impact of the risk genotype, as well as homeostasis between folate and vitamin B12 in TT homozygotes, seems to be attenuated. CONCLUSION: Although the MTHFR 677TT genotype is not directly related to a higher BMI in Polish adults, it has a detrimental effect on folate concentrations in individuals with high BMI values.

12.
Int J Mol Sci ; 23(24)2022 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-36555333

RESUMO

Copper complexes with 1,3-disubstituted thiourea derivatives, all containing 3-(trifluoromethyl)phenyl tail and 1-alkyl/halogen-phenyl substituent, were synthesized. The experimental spectroscopic studies and theoretical calculation revealed that two ligands coordinate to Cu(II) in a bidentate fashion via thiocarbonyl S and deprotonated N atoms of thiourea moiety. Such monomers are characteristic of alkylphenylthiourea complexes, whereas the formation of a sandwich-type dimer is observed for halogeno derivatives. For the first time, the structural identifications of CuN2S2-based complexes using experimental and theoretical X-ray absorption near edge structure are demonstrated. The dimeric halogeno derivatives showed higher antimicrobial activity in comparison with alkylphenylthiourea complexes. The Cu(II) complex of 1-(4-chloro-3-nitrophenyl)-3-[3-(trifluoromethyl)phenyl]thiourea was active against 19 strains of methicillin-resistant Staphylococci (MIC = 2 µg/mL). This derivative acted as a dual inhibitor of DNA gyrase and topoisomerase IV isolated from Staphylococcus aureus. Additionally, complexes of halogenphenylthiourea strongly inhibited the growth of mycobacteria isolated from tuberculosis patients, even fourfold stronger than the reference isoniazid. The complexes exerted weak to moderate antitumor activity (towards SW480, SW620, and PC3) being non-toxic towards normal HaCaT cells.


Assuntos
Complexos de Coordenação , Feniltioureia , Humanos , Antibacterianos/química , Tioureia/farmacologia , Tioureia/química , DNA Topoisomerase IV , DNA Girase , Cobre/química , Complexos de Coordenação/química
13.
Int J Mol Sci ; 23(11)2022 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-35682940

RESUMO

Novel conjugates (CP) of moxifloxacin (MXF) with fatty acids (1m-16m) were synthesized with good yields utilizing amides chemistry. They exhibit a more pronounced cytotoxic potential than the parent drug. They were the most effective for prostate cancer cells with an IC50 below 5 µM for respective conjugates with sorbic (2m), oleic (4m), 6-heptenoic (10m), linoleic (11m), caprylic (15m), and stearic (16m) acids. All derivatives were evaluated against a panel of standard and clinical bacterial strains, as well as towards mycobacteria. The highest activity towards standard isolates was observed for the acetic acid derivative 14m, followed by conjugates of unsaturated crotonic (1m) and sorbic (2m) acids. The activity of conjugates tested against an expanded panel of clinical coagulase-negative staphylococci showed that the compound (14m) was recognized as a leading structure with an MIC of 0.5 µg/mL denoted for all quinolone-susceptible isolates. In the group of CP derivatives, sorbic (2) and geranic (3) acid amides exhibited the highest bactericidal potential against clinical strains. The M. tuberculosis Spec. 210 strain was the most sensitive to sorbic (2m) conjugate and to conjugates with medium- and long-chain polyunsaturated acids. To establish the mechanism of antibacterial action, selected CP and MXF conjugates were examined in both topoisomerase IV decatenation assay and the DNA gyrase supercoiling assay, followed by suitable molecular docking studies.


Assuntos
Ciprofloxacina , Ácidos Graxos , Amidas , Antibacterianos/química , Antibacterianos/farmacologia , Ciprofloxacina/química , Ciprofloxacina/farmacologia , DNA Girase , Fluoroquinolonas/farmacologia , Humanos , Masculino , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Moxifloxacina/farmacologia
14.
Obes Surg ; 32(2): 428-440, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34813039

RESUMO

PURPOSE: Fatty acids (FA), particularly polyunsaturated (PUFA) ones, are involved in the regulation of glycemic control, lipid metabolism, and inflammation. The aim of the study was to assess patient FA profile in relation to obesity, lipid and carbohydrate metabolism disturbances, and weight loss. MATERIALS AND METHODS: The studied group consisted of 51 patients with extreme obesity, 23 of whom achieved radical weight reduction within 1 year after a laparoscopic sleeve gastrectomy (LSG). FA levels were determined using gas chromatography with flame ionization detection. RESULTS: Patients with extreme obesity and higher serum PUFA content have lower serum levels of SFA and MUFA (especially myristic, palmitic, lignoceric acids and palmitoleic, oleic acids), as well as lower triglyceride and higher HDL-cholesterol concentrations and it was not influenced by CEPT Taq1B variant. At baseline, the fatty acid profile of patients with type II diabetes differ from patients with dyslipidemia. In patients who had lost weight, significantly lower levels of selected saturated FA and major trans-fatty acid, elaidic, were found. Moreover, the proportion of PUFA was increased. CONCLUSION: In extreme obesity, higher PUFA exert their favorable effects on serum lipids. Significant weight reduction after the bariatric surgery is associated with beneficial changes in the fatty acid profile.


Assuntos
Diabetes Mellitus Tipo 2 , Obesidade Mórbida , Ácidos Graxos , Humanos , Obesidade/cirurgia , Obesidade Mórbida/cirurgia , Redução de Peso
15.
Arch Med Sci ; 17(6): 1643-1650, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34900044

RESUMO

INTRODUCTION: Uterine fibroids (UFs) are benign tumors which are derived from the smooth muscle cells of the uterus. Recent studies have demonstrated that the development of UFs can be particularly related to vitamin D and its receptor. Vitamin D comprises a group of fat-soluble steroid compounds which exert powerful, pleiotropic effects all over the human body. These actions are mediated by a specific type of receptor - vitamin D receptor (VDR). Recent findings have focused on the possible role of VDR genetic variations in the development of several types of diseases, e.g. autoimmune system diseases, various cancers and infections. MATERIAL AND METHODS: The aim of the study was to evaluate the association between rs731236, rs1544410, and rs2228570 polymorphisms in the VDR (vitamin D receptor) gene and the incidence of UFs in Caucasian women. A total of 197 patients (114 fibroid-positive and 83 controls) were included in this retrospective cohort study. VDR gene polymorphisms rs731236 (TaqI), rs1544410 (BsmI) and rs2228570 (FokI) were determined using TaqMan and Simple Probes. RESULTS: No statistically significant differences in the occurrence of selected VDR polymorphisms were observed between UF-positive women and healthy controls. CONCLUSIONS: We found no association between rs731236, rs1544410, and rs2228570 VDR polymorphisms and UF incidence in Caucasian women. Larger sample size and multi-ethnic studies are necessary to investigate the matter further.

16.
J Clin Med ; 10(21)2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34768607

RESUMO

In our previous study, we showed that sildenafil citrate (SC), a selective PDE5A blocker, modulated NK cell activity in patients with recurrent pregnancy loss, which correlated with positive pregnancy outcomes. It was found that NK cells had a pivotal role in decidualization, angiogenesis, spiral artery remodeling, and the regulation of trophoblast invasion. Thus, in the current study, we determined the effects of SC on angiogenic factor expression and production, as well as idNK cell activity in the presence of nitric synthase blocker L-NMMA. Methods: NK cells (CD56+) were isolated from the peripheral blood of 15 patients and 15 fertile women on MACS columns and cultured in transformation media containing IL-15, TGF-ß, and AZA-a methylation agent-for 7 days in hypoxia (94% N2, 1% O2, 5% CO2). Cultures were set up in four variants: (1) with SC, (2) without SC, (3) with NO, a synthase blocker, and (4) with SC and NO synthase blocker. NK cell activity was determined after 7 days of culturing as CD107a expression after an additional 4h of stimulation with K562 erythroleukemia cells. The expression of the PDE5A, VEGF-A, PIGF, IL-8, and RENBP genes was determined with quantitative real-time PCR (qRT-PCR) using TaqMan probes and ELISA was used to measure the concentrations of VEGF-A, PLGF, IL-8, Ang-I, Ang-II, IFN-γ proteins in culture supernatants after SC supplementation. Results: SC downregulated PDE5A expression and had no effect on other studied angiogenic factors. VEGF-A expression was increased in RPL patients compared with fertile women. Similarly, VEGF production was enhanced in RPL patients' supernatants and SC increased the concentration of PIGF in culture supernatants. SC did not affect the expression or concentration of other studied factors, nor idNK cell activity, regardless of NO synthase blockade.

17.
Int J Mol Sci ; 23(1)2021 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-35008805

RESUMO

Eleven novel imide-tetrazoles were synthesized. In the initial stage of research, in silico structure-based pharmacological prediction was conducted. All compounds were screened for antimicrobial activity using standard and clinical strains. Within the studied group, compounds 1-3 were recognized as leading structures with the most promising results in antimicrobial studies. Minimal inhibitory concentration values for compounds 1, 2, 3 were within the range of 0.8-3.2 µg/mL for standard and clinical Gram-positive and Gram-negative bacterial strains, showing in some cases higher activity than the reference Ciprofloxacin. Additionally, all three inhibited the growth of all clinical Staphylococci panels: Staphylococcus aureus (T5592; T5591) and Staphylococcus epidermidis (5253; 4243) with MIC values of 0.8 µg/mL. Selected compounds were examined in topoisomerase IV decatenation assay and DNA gyrase supercoiling assay, followed by suitable molecular docking studies to explore the possible binding modes. In summary, the presented transition from substrate imide-thioureas to imide-tetrazole derivatives resulted in significant increase of antimicrobial properties. The compounds 1-3 proposed here provide a promising basis for further exploration towards novel antimicrobial drug candidates.


Assuntos
Antibacterianos/farmacologia , DNA Girase/metabolismo , DNA Topoisomerase IV/antagonistas & inibidores , Staphylococcus aureus/enzimologia , Tetrazóis/farmacologia , Inibidores da Topoisomerase II/farmacologia , DNA Topoisomerase IV/metabolismo , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Espectroscopia de Prótons por Ressonância Magnética , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificação
18.
Obes Surg ; 30(10): 3974-3981, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32557384

RESUMO

BACKGROUND: The aim of the study was to assess changes in body composition in patients subjected to laparoscopic sleeve gastrectomy (LSG). METHODS: Changes in body composition following LSG were determined in a group of 155 patients with obesity (117 women and 38 men), with dual-energy X-ray absorptiometry (DXA). Whole body fat mass (FM) and lean body mass (LBM) were determined, and abdominal fat mass (AbdF) was assessed within the region extending from the top of the pubic bone up to the line between 12th thoracic and 1st lumbar vertebras. RESULTS: Over the period of 12 months following LSG, body mass index decreased by 28.2 ± 9.0% (p < 0.001). The reduction of body weight by 35.4 ± 12.6 kg (p < 0.001) was the result of a decrease in FM by 23.9 ± 8.9 kg (p < 0.001) and LBM by 10.5 ± 3.8 kg (p < 0.001). AbdF decreased from 13.2 ± 3.1 to 8.2 ± 2.7 kg (p < 0.001), but abdominal fat to total fat mass ratio increased from 24.9 ± 4.7 to 28.0 ± 5.8% (p < 0.001). The loss of AbdF was more pronounced in men than in women. The rate of FM loss was attenuated with patients' age. CONCLUSIONS: Over the period of 12 months following LSG, the reduction of FM was more than twice as much as decrease of LBM. The loss of AbdF was slower than a loss of peripheral subcutaneous fat.


Assuntos
Laparoscopia , Obesidade Mórbida , Composição Corporal , Índice de Massa Corporal , Feminino , Gastrectomia , Humanos , Masculino , Obesidade/cirurgia , Obesidade Mórbida/cirurgia
19.
J Trace Elem Med Biol ; 59: 126450, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31931255

RESUMO

The aim of the study was to evaluate the effect of dietary supplementation with chosen minerals (Zn, Se, Fe) on expression of selected cytokines (IL-1, IL-6, TNFα) in spleen of rats and on their concentrations in rat serum under inflammatory and pathological conditions obtained by implantation of prostate cancer cells (LnCaP). Serum levels of metabolites of arachidonic, eicosapentaenoic and linoleic acids (hydroxyeicosatetraenoic, hydroxyeicosapentaenoic and hydroxyoctadecadienoic acids, respectively), as compounds involved in inflammation and cancer development, were also investigated. Male rats were randomised into dietary groups supplemented with Zn, Se or Fe. Prostate cancer cells were implanted to some rats in each group. The study demonstrated that minerals supplemented with the diet may exert various effects on an organism. Selenium, zinc and iron influence pro-inflammatory cytokine expression, what leads to stimulation of inflammation. They also affect synthesis of arachidonic and linoleic acid metabolites that exert pro-inflammatory action and enable cancer development and metastasis.


Assuntos
Citocinas/sangue , Inflamação/sangue , Ferro/sangue , Neoplasias da Próstata/sangue , Selênio/sangue , Zinco/sangue , Animais , Citocinas/genética , Suplementos Nutricionais , Modelos Animais de Doenças , Inflamação/metabolismo , Inflamação/patologia , Ferro/administração & dosagem , Masculino , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Ratos , Ratos Sprague-Dawley , Selênio/administração & dosagem , Zinco/administração & dosagem
20.
Trends Hear ; 23: 2331216519878539, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31588855

RESUMO

Tinnitus masking patterns have long been known to differ from those used for masking external sound. In the present study, we compared the shape of tinnitus tuning curves (TTCs) to psychophysical tuning curves (PTCs), the latter using as a target, an external sound that mimics the tinnitus characteristics. A secondary goal was to compare sound levels required to mask tinnitus to those required to mask tinnitus-mimicking sounds. The TTC, PTC, audiometric thresholds, tinnitus pitch, and level matching results of 32 tinnitus patients were analyzed. Narrowband noise maskers were used for both PTC and TTC procedures. Patients were categorized into three groups based on a combination of individual PTC-TTC results. Our findings indicate that in 41% of cases, the PTC was sharp (V shape), but the TTC showed a flat configuration, suggesting that the tinnitus-related activity in that subgroup does not behave as a regular stimulus-induced activity. In 30% of cases, V-shape PTC and TTC were found, indicating that the tinnitus-related activity may share common properties with stimulus-induced activity. For a masker centered at the tinnitus frequency, the tinnitus was more difficult to mask than the mimicking tone in 72% of patients; this was particularly true for the subset with V-shape PTCs and flat TTCs. These results may have implications for subtyping tinnitus and acoustic therapies, in particular those targeting the tinnitus frequency.


Assuntos
Audiometria , Psicoacústica , Zumbido , Acústica , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Ruído , Mascaramento Perceptivo , Som , Zumbido/diagnóstico , Zumbido/terapia
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