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1.
Int J Mol Sci ; 25(2)2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38256272

RESUMO

Cornelian cherry (Cornus mas L.) fruits, abundant in iridoids and anthocyanins, are natural products with proven beneficial impacts on the functions of the cardiovascular system and the liver. This study aims to assess and compare whether and to what extent two different doses of resin-purified cornelian cherry extract (10 mg/kg b.w. or 50 mg/kg b.w.) applied in a cholesterol-rich diet rabbit model affect the levels of sterol regulatory element-binding protein 1c (SREBP-1c) and CCAAT/enhancer binding protein α (C/EBPα), and various liver X receptor-α (LXR-α), peroxisome proliferator-activated receptor-α (PPAR-α), and peroxisome proliferator-activated receptor-γ (PPAR-γ) target genes. Moreover, the aim is to evaluate the resistive index (RI) of common carotid arteries (CCAs) and aortas, and histopathological changes in CCAs. For this purpose, the levels of SREBP-1c, C/EBPα, ATP-binding cassette transporter A1 (ABCA1), ATP-binding cassette transporter G1 (ABCG1), fatty acid synthase (FAS), endothelial lipase (LIPG), carnitine palmitoyltransferase 1A (CPT1A), and adiponectin receptor 2 (AdipoR2) in liver tissue were measured. Also, the levels of lipoprotein lipase (LPL), visceral adipose tissue-derived serine protease inhibitor (Vaspin), and retinol-binding protein 4 (RBP4) in visceral adipose tissue were measured. The RI of CCAs and aortas, and histopathological changes in CCAs, were indicated. The oral administration of the cornelian cherry extract decreased the SREBP-1c and C/EBPα in both doses. The dose of 10 mg/kg b.w. increased ABCA1 and decreased FAS, CPT1A, and RBP4, and the dose of 50 mg/kg b.w. enhanced ABCG1 and AdipoR2. Mitigations in atheromatous changes in rabbits' CCAs were also observed. The obtained outcomes were compared to the results of our previous works. The beneficial results confirm that cornelian cherry fruit extract may constitute a potentially effective product in the prevention and treatment of obesity-related disorders.


Assuntos
Cornus , Lagomorpha , Extratos Vegetais , Animais , Coelhos , Antocianinas , Transportadores de Cassetes de Ligação de ATP , Proteína alfa Estimuladora de Ligação a CCAAT/genética , Cornus/química , Dieta , Frutas/química , Fígado , Receptores X do Fígado/genética , Extratos Vegetais/farmacologia , PPAR alfa/genética , PPAR gama/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/genética
2.
Int J Mol Sci ; 24(4)2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36835296

RESUMO

Atherogenesis leads to the development of atherosclerosis, a progressive chronic disease characterized by subendothelial lipoprotein retention and endothelial impairment in the arterial wall. It develops mainly as a result of inflammation and also many other complex processes, which arise from, among others, oxidation and adhesion. Cornelian cherry (Cornus mas L.) fruits are abundant in iridoids and anthocyanins-compounds with potent antioxidant and anti-inflammatory activity. This study aimed to determine the effect of two different doses (10 mg and 50 mg per kg of body weight, respectively) of iridoid and anthocyanin-rich resin-purified Cornelian cherry extract on the markers that are important in the progress of inflammation, cell proliferation and adhesion, immune system cell infiltration, and atherosclerotic lesion development in a cholesterol-rich diet rabbit model. We used biobank blood and liver samples that were collected during the previous original experiment. We assessed the mRNA expression of MMP-1, MMP-9, IL-6, NOX, and VCAM-1 in the aorta, and the serum levels of VCAM-1, ICAM-1, CRP, PON-1, MCP-1, and PCT. The application of the Cornelian cherry extract at a dose of 50 mg/kg bw resulted in a significant reduction in MMP-1, IL-6, and NOX mRNA expression in the aorta and a decrease in VCAM-1, ICAM-1, PON-1, and PCT serum levels. The administration of a 10 mg/kg bw dose caused a significant decrease in serum ICAM-1, PON-1, and MCP-1. The results indicate the potential usefulness of the Cornelian cherry extract in the prevention or treatment of atherogenesis-related cardiovascular diseases, such as atherosclerosis or metabolic syndrome.


Assuntos
Aterosclerose , Colesterol na Dieta , Cornus , Dieta Aterogênica , Extratos Vegetais , Animais , Coelhos , Antocianinas/uso terapêutico , Aterosclerose/tratamento farmacológico , Frutas , Inflamação/tratamento farmacológico , Molécula 1 de Adesão Intercelular , Interleucina-6 , Iridoides/uso terapêutico , Metaloproteinase 1 da Matriz , Extratos Vegetais/uso terapêutico , RNA Mensageiro , Molécula 1 de Adesão de Célula Vascular
3.
Molecules ; 28(7)2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-37049797

RESUMO

Given that one of the crucial events in the pathogenesis of inflammatory bowel disease is the loss of homeostasis between Th17 and Treg cells, targeting the specific molecules of the Th17/Treg axis developmental pathway is a promising strategy for inflammatory bowel disease prevention and treatment. The current study aimed to assess the impact of cornelian cherry (Cornus mas L.) extract, rich in iridoids and polyphenols known for their potential anti-inflammatory activity, at two doses (20 or 100 mg/kg) on the crucial factors for Th17/Treg cell differentiation in the course of experimental colitis and compare this action with that of sulfasalazine. This study was conducted on the biobank colon tissue samples collected during the previous original experiment, in which colitis in rats was induced by trinitrobenzenesulfonic acid (TNBS). The levels of IL-6, RORγt, total STAT3, p-STAT3, and Foxp3 were determined by ELISA. The expression of PIAS3 mRNA was quantified by qPCR. Cornelian cherry extract at a dose of 100 mg/kg counteracted the TNBS-induced elevation of IL-6, RORγt, and p-STAT3 levels and a decrease in Foxp3 level and PIAS3 mRNA expression, while given concomitantly with sulfasalazine was more effective than sulfasalazine alone in reversing the TNBS-induced changes in IL-6, RORγt, total STAT3, p-STAT3, Foxp3 levels, and PIAS3 mRNA expression. The beneficial effect of cornelian cherry extract on experimental colitis may be due to its immunomodulatory activity reflected by the influence on factors regulating the Th17/Treg axis.


Assuntos
Colite , Cornus , Doenças Inflamatórias Intestinais , Ratos , Animais , Linfócitos T Reguladores , Ácido Trinitrobenzenossulfônico/efeitos adversos , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Interleucina-6/farmacologia , Sulfassalazina/farmacologia , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Células Th17 , Modelos Animais de Doenças
4.
Proc Natl Acad Sci U S A ; 115(28): E6477-E6486, 2018 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-29934401

RESUMO

PA28γ is a nuclear activator of the 20S proteasome involved in the regulation of several essential cellular processes, such as cell proliferation, apoptosis, nuclear dynamics, and cellular stress response. Unlike the 19S regulator of the proteasome, which specifically recognizes ubiquitylated proteins, PA28γ promotes the degradation of several substrates by the proteasome in an ATP- and ubiquitin-independent manner. However, its exact mechanisms of action are unclear and likely involve additional partners that remain to be identified. Here we report the identification of a cofactor of PA28γ, PIP30/FAM192A. PIP30 binds directly and specifically via its C-terminal end and in an interaction stabilized by casein kinase 2 phosphorylation to both free and 20S proteasome-associated PA28γ. Its recruitment to proteasome-containing complexes depends on PA28γ and its expression increases the association of PA28γ with the 20S proteasome in cells. Further dissection of its possible roles shows that PIP30 alters PA28γ-dependent activation of peptide degradation by the 20S proteasome in vitro and negatively controls in cells the presence of PA28γ in Cajal bodies by inhibition of its association with the key Cajal body component coilin. Taken together, our data show that PIP30 deeply affects PA28γ interactions with cellular proteins, including the 20S proteasome, demonstrating that it is an important regulator of PA28γ in cells and thus a new player in the control of the multiple functions of the proteasome within the nucleus.


Assuntos
Autoantígenos/metabolismo , Núcleo Celular/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteínas/metabolismo , Autoantígenos/genética , Núcleo Celular/genética , Células HeLa , Humanos , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Complexo de Endopeptidases do Proteassoma/genética , Ligação Proteica , Domínios Proteicos , Proteínas/genética
5.
Andrologia ; 53(6): e14058, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33792946

RESUMO

In this study, we investigated the influence of long-term administration of stiripentol on sex hormones and semen quality in young Wistar rats. Investigated animals received for 6 months either stiripentol or saline solution. After one month, stiripentol increased temporarily serum level of testosterone (p < 0.05) and FSH (p < 0.01). However, after 6 months levels of testosterone, FSH, LH, prolactin and SHBG were comparable in both groups. After 6 months, semen analysis did not reveal differences in sperm concentration, total sperm count and sperm motility between groups. However, stiripentol increased the rate of head defect (p < 0.001) and midpiece abnormalities (p < 0.05). Flow cytometry revealed higher percentage of live cells without lipid peroxidation (p < 0.00001) and higher percentage of live spermatozoa with intact acrosomes (p < 0.000001) in rats receiving stiripentol. There was no significant difference between groups in sperm mitochondrial activity and DNA fragmentation index. However, percentage of high DNA stainability cells was increased in stiripentol group (p < 0.001). The data showed that stiripentol does not cause obvious disturbances in young rat's semen. Detected changes in semen morphology and chromatin structure need further explanation, and their influence on rat's fertility should be evaluated.


Assuntos
Análise do Sêmen , Motilidade dos Espermatozoides , Animais , Anticonvulsivantes , Dioxolanos , Hormônio Foliculoestimulante , Humanos , Masculino , Ratos , Ratos Wistar , Sêmen , Contagem de Espermatozoides , Espermatozoides , Testosterona
6.
Int J Mol Sci ; 22(13)2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34281215

RESUMO

Bone structure abnormalities are increasingly observed in patients chronically treated with antiepileptic drugs (AEDs). The majority of the available data concern older conventional AEDs, while the amount of information regarding newer AEDs, including stiripentol, is limited. The aim of the study was to assess the effect of stiripentol on bones. For 24 weeks, male Wistar rats, received 0.9% sodium chloride (control group) or stiripentol (200 mg/kg/day) (STP group). In the 16th week of the study, we detected lower serum PINP levels in the STP group compared to the control group. In the 24th week, a statistically significant lower 1,25-dihydroxyvitamin D3 level, higher inorganic phosphate level and higher neutrophil gelatinase-associated lipocalin (NGAL) levels in serum were found in the STP group compared to the control. Micro X-ray computed tomography of the tibias demonstrated lower bone volume fraction, lower trabecular thickness, higher trabecular pattern factor and a higher structure model index in the stiripentol group. Considering the results of this experiment on rats which suggests that long-term administration of stiripentol may impair the cancellous bone microarchitecture, further prospective human studies seem to be justified. However, monitoring plasma vitamin D, calcium, inorganic phosphate and kidney function in patients on long-term stiripentol therapy may be suggested.


Assuntos
Anticonvulsivantes/efeitos adversos , Osso e Ossos/efeitos dos fármacos , Dioxolanos/efeitos adversos , Animais , Densidade Óssea/efeitos dos fármacos , Osso e Ossos/diagnóstico por imagem , Masculino , Distribuição Aleatória , Ratos Wistar , Microtomografia por Raio-X
7.
Reumatologia ; 56(6): 354-361, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30647481

RESUMO

OBJECTIVES: To assess the importance of ultrasound (US) examination of joints in hands and feet in patients with early arthritis and perform comparative analysis of the diagnostic value of US examination for 8, 12 and 52 selected joints. MATERIAL AND METHODS: 123 patients (87 women, 36 men) with arthritis lasting less than 12 months, naive to disease-modifying anti-rheumatic drugs and glucocorticosteroids. Necessary differential diagnostics was performed for each patient. After the preliminary analysis, 72 patients met the classification criteria for rheumatoid arthritis (RA) according to ACR/EULAR of 2010, and undifferentiated arthritis (UA) was diagnosed in 51 patients. UA patients were followed up after 6 and 12 months, and verification of the initial diagnosis yielded the following groups of patients: patients meeting classification criteria for RA, patients with maintained diagnosis of UA, patients in remission, and patients with other diagnoses. Ultrasound examination was performed considering the volume of joint effusion (JE), synovial membrane hypertrophy (GS), and synovial membrane hyperaemia assessed by power Doppler (PD). Results were assessed using the semi-qualitative scale. Coefficients being the sum of US scores for the assessment of JE, GS and PD for 52 and 12 joints in hands and feet, and 8 joints in hands were determined for the purpose of the study. RESULTS: In patients meeting classification criteria for RA during the initial assessment the US examination yielded significantly higher PD-52I, PD-12I and PD-8I coefficients. In UA patients who were diagnosed with RA after 12 months, the GS-8I coefficient was significantly higher. CONCLUSIONS: Ultrasonography is a valuable tool in diagnostics of early arthritis. The GS assessment has prognostic value for UA patients. The assessment of 8 or 12 selected joints is often sufficient for the diagnostics of patients with early arthritis.

8.
Int J Mol Sci ; 18(7)2017 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-28677621

RESUMO

Genes involved in regulation of the nuclear factor-κB (NF-κB)-pathway are suggested to play a role in pathogenesis of rheumatoid arthritis (RA). In the present study, genetic polymorphisms of TLR2, TLR4, TLR9 and NF-κB1 genes were investigated to assess their associations with RA susceptibility, progression and response to anti-TNF-α therapy. A group of 110 RA patients and 126 healthy individuals were genotyped for TLR2 (rs111200466), TLR4 (rs4986790, rs4986791), TLR9 (rs5743836, rs187084) and NF-κB1 (rs28362491) alleles. The presence of the TLR9 -1486 T variant (p < 0.0001) and its homozygosity (p < 0.0001) were found to be associated with disease susceptibility. The TLR9 -1237 C allele was associated with predisposition to RA in females only (p = 0.005). Moreover, the TLR4 rs4986791 G (rs4986790 T) alleles were more frequently detected among patients with the stage IV disease (p = 0.045), and were associated with more effective response to anti-TNF-α therapy (p = 0.012). More efficient response to anti-TNF-α treatment was also observed in patients with del within the NF-κB1 gene (p = 0.047), while for the TLR9 -1486 T homozygotes, the treatment was ineffective (p = 0.018). TLR polymorphisms affect disease susceptibility and response to therapy with TNF-α inhibitors in RA patients of Caucasian origin.


Assuntos
Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , NF-kappa B/metabolismo , Polimorfismo de Nucleotídeo Único , Transdução de Sinais , Adolescente , Adulto , Idoso , Alelos , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/farmacologia , Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , NF-kappa B/genética , Fatores de Risco , Receptores Toll-Like/genética , Receptores Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/metabolismo , Adulto Jovem
9.
Postepy Hig Med Dosw (Online) ; 69: 1291-8, 2015 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-26671920

RESUMO

BACKGROUND: The etiology of axial spondyloarthritis (axSpA) is not fully elucidated. Research continues in determining the mechanisms responsible for initiation of the disease process, its maintenance and development. OBJECTIVES: The aim of this study was to evaluate the expression of transcription factors STAT (signal transducer and activator of transcription) and NF-κB (nuclear factor kappa B) as well as Janus kinase3 (JAK3) in the peripheral blood leukocytes. We also analyzed the connection between the degree of activation of transcription factors and the disease activity. MATERIAL/METHODS: The study involved 46 patients with axSpA and 19 healthy individuals who comprised the control group. The expression of NF-κB, STAT1, STAT3, STAT4, STAT5, STAT6, and JAK3 in peripheral blood leukocytes was assessed. To determine the degree of activation of transcription factors STAT-s and NF-κB and JAK3 kinase, the immunocytochemistry method was used. For location of the factors, the primary monoclonal anti-NF-κB, anti-JAK3 and polyclonal anti-STAT-s antibodies were used (Chemicon International, USA, Abcam, Cambridge, UK), and the set of antibodies Novocastain Super ABC Kit (Novocastra, UK). RESULTS: Expression of STAT1, STAT3, STAT4, STAT5, STAT6, NF-κB and JAK3 was statistically higher in the group of patients with axSpA than in the control group. There was a positive correlation with ESR values and expression of STAT4. There was no correlation between STAT, NF-κB, and JAK3 expression and ASDAS, BASDAI, and BASFI. Nine patients were treated with TNF-α inhibitors. The expression of NF-κB and STAT6 was higher in the group treated with TNF-α inhibitors, even though disease activity in these patients was shown to be lower than in those not receiving such treatment (ASDAS = 1.34±0.51 vs. 3.52±0.90, BASDAI = 2.34±1.92 vs. 5.51±2.41). CONCLUSIONS: In the group of patients with axSpA compared with the control group, higher expression of the transcription factors STAT and NF-κB as well as JAK3 was observed. Due to its crucial roles in inflammation and autoimmunity, STAT4 may have promise as an effective therapeutic target for axSpA.


Assuntos
Janus Quinase 3/genética , Leucócitos/metabolismo , NF-kappa B/genética , Fatores de Transcrição STAT/genética , Espondilartrite/metabolismo , Adulto , Idoso , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Adulto Jovem
10.
Reumatologia ; 53(1): 9-13, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-27407219

RESUMO

OBJECTIVES: Current studies concentrate on the cytokine network and its role in the pathogenesis of spondyloarthritis (SpA). In this study, we analyzed whether the serum cytokine profile (interleukins: IL-10, IL-11, IL-12, IL-15, IL-17, IL-23 and IL-33) correlates with demographic data, clinical manifestations, disease activity and treatment outcome in a group of patients with axial spondyloarthritis. MATERIAL AND METHODS: Forty-nine patients with an established diagnosis of axial spondyloarthritis (aSpA) and 19 healthy volunteers as controls were enrolled in the study. Clinical evaluation included patient's medical history, 44 joint count, back pain intensity and global disease activity in the preceding week (VAS), the duration of morning stiffness and blood tests. Disease activity was assessed using BASDAI and ASDAS-CRP. Serum concentration of IL-10, IL-11, IL-12, IL-15, IL-17, IL-23 and IL-33 was determined. RESULTS: In patients with aSpA, elevated serum concentration of IL-10, IL-15, IL-17 and IL-23 was detected. In the aSpA group we detected higher values of serum concentration of IL-23 and IL-33 in the subgroup with anterior uveitis (83.1 ±184.0 pg/ml vs. 14.0 ±17.1 pg/ml, p < 0.0001 and 45.5 ±71.9 pg/ml vs. 18.4 ±14.3 pg/ml, p < 0.0001, respectively). Additionally, in the subgroup with peripheral arthritis, elevation of serum concentration of IL-12 (249.3 ±246.9 pg/ml vs. 99.9 ±105.9 pg/ml, p = 0.0001) was detected. Patients with preradiological SpA had higher serum concentration of IL-17 than patients with established diagnosis of AS (6.37 ±8.50 pg/ml vs. 2.04 ±2.98 pg/ml, p = 0.0295). No differences in serum concentration of analyzed cytokines were found between the subgroup with low to moderate disease activity and the subgroup with high to very high disease activity. CONCLUSIONS: We report that in aSpA patients, compared to controls, elevated serum concentrations of IL-10, IL-15, IL-17 and IL-23 were observed. Some cytokines may predispose to a more severe course of aSpA.

11.
BMJ Open ; 13(7): e069252, 2023 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-37423634

RESUMO

OBJECTIVE: To complete a cultural adaptation of a UK evidence-based problem-solving intervention to support Polish prisoners at risk of suicidal behaviour. DESIGN: A cross-sectional survey participatory design using an Ecological Validity Model. SETTING: The study was a collaboration between: the Academy of Justice, in Warsaw, the University of Lodz, two Polish prisons (ZK Raciborz and ZK Klodzko) and the University of York (UK). METHODS: The adaptation process included an examination of the use of language, metaphors and content (ie, culturally appropriate and syntonic language), the changing of case study scenarios (relevance and acceptability) and maintenance of the theoretical underpinning of the problem-solving model (intervention comprehensibility and completeness). Four stages used: (1) a targeted demonstration for Polish prison staff, (2) a wider audit of the skills with Polish prison staff and students, (3) forward and back-translation of the adapted package, and (4) two iterative consultations with participants from stages (1) and (2) and prison officers from two Polish prisons. PARTICIPANTS: Self-selecting volunteer participants included: targeted prison staff (n=10), prison staff from the wider Polish penitentiary system (n=39), students from the University of Lodz (n=28) and prison officers from two Polish prisons (n=12). MAIN OUTCOMES AND MEASURES: Acceptability and feasibility of the training package, reported in a series of knowledge user surveys. RESULTS: The recognised benefits of using the skills within the training package included: enhancing communication, reflective development, collaborative working, changing behaviour, empowering decision-making, relevance to crisis management situations and use of open-ended questions. The skills were endorsed to be used as part of future penitentiary training for prison officers in Poland. CONCLUSIONS: The skills had widespread appeal for use across the Polish penitentiary system. The materials were deemed relevant while adhering to the comprehensibility of the intervention. Further evaluation of the intervention should be explored using a randomised controlled trial design.


Assuntos
Prisioneiros , Ideação Suicida , Humanos , Estudos Transversais , Polônia , Prisões , Idioma , Reino Unido
12.
Artigo em Inglês | MEDLINE | ID: mdl-35742733

RESUMO

BACKGROUND AND AIM: The use of dietary supplements (DS) and over-the-counter (OTC) drugs is increasing every year. The COVID-19 pandemic might additionally influence the use of such preparations. The study aimed to investigate factors influencing the use of dietary supplements (DS), including stress-relieving supplements, by the students. METHODS: In the cross-sectional study, 624 students of the Wroclaw Medical University in Poland, from the second to the last year of studies, completed the anonymous questionnaire, consisting of 22 items, about the use of DS/OTC drugs during the academic year 2020/2021. Obtained data were analyzed using Pearson's chi-square test, the U-Mann Whitney test, the Kruskal-Wallis test with the post-hoc analysis, and with logistic regression. RESULTS: About 70% of students declared the use of any DS, 33% used DS for stress, anxiety, depression, or sleeping problems, and 59% used other DS. The most important factors influencing the decision to take any kind of DS were Division (p = 0.0001, odds ratio [OR]: 0.35, and confidence interval [CI]: 0.21-0.59), a self-estimated level of stress (p = 0.014, OR: 1.13, CI: 1.03-1.25), and self-estimated level of knowledge about DS (p = 0.0000, OR: 1.31, CI: 1.19-1.36). In the case of students taking DS for stress, anxiety, depression, or sleeping problems, the level of stress and the declared knowledge had the greatest impact on the decision for such a use of DS (p = 0.0001, OD: 1.24, CI: 1.11-1.39 and p = 0.0000, OD: 1.35, CI: 1.22-1.5, respectively). The COVID-19 pandemic did not change the pattern of DS/OTC drug usage in about 33% of students. Those who started taking DS during the pandemic accounted for 19% of all students. CONCLUSIONS: The use of DS is common among Wroclaw Medical University students with some differences between subgroups of respondents. Additionally, despite declared good knowledge about DS, most students declare the need to learn more about them.


Assuntos
COVID-19 , Transtornos do Sono-Vigília , Estudantes de Medicina , COVID-19/epidemiologia , Estudos Transversais , Depressão , Suplementos Nutricionais , Humanos , Medicamentos sem Prescrição/uso terapêutico , Pandemias , Polônia/epidemiologia , Universidades
13.
Pharmacol Rep ; 74(5): 890-908, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36129673

RESUMO

BACKGROUND: Alzheimer's disease (AD) is considered the most common cause of dementia among the elderly. One of the modifiable causes of AD is neuroinflammation. The current study aimed to investigate the influence of new tricyclic 1,2-thiazine derivatives on in vitro model of neuroinflammation and their ability to cross the blood-brain barrier (BBB). METHODS: The potential anti-inflammatory effect of new tricyclic 1,2-thiazine derivatives (TP1, TP4, TP5, TP6, TP7, TP8, TP9, TP10) was assessed in SH-SY5Y cells differentiated to the neuron-like phenotype incubated with bacterial lipopolysaccharide (5 or 50 µg/ml) or THP-1 microglial cell culture supernatant using MTT, DCF-DA, Griess, and fast halo (FHA) assays. Additionally, for cultures preincubated with 50 µg/ml lipopolysaccharide (LPS), a cyclooxygenase (COX) activity assay was performed. Finally, the potential ability of tested compounds to cross the BBB was evaluated by computational studies. Molecular docking was performed with the TLR4/MD-2 complex to assess the possibility of binding the tested compounds in the LPS binding pocket. Prediction of ADMET parameters (absorption, distribution, metabolism, excretion and toxicity) was also conducted. RESULTS: The unfavorable effect of LPS and co-culture with THP-1 cells on neuronal cell viability was counteracted with TP1 and TP4 in all tested concentrations. Tested compounds reduced the oxidative and nitrosative stress induced by both LPS and microglia activation and also reduced DNA damage. Furthermore, new derivatives inhibited total COX activity. Additionally, new compounds would cross the BBB with high probability and reach concentrations in the brain not lower than in the serum. The binding affinity at the TLR4/MD-2 complex binding site of TP4 and TP8 compounds is similar to that of the drug donepezil used in Alzheimer's disease. The ADMET analysis showed that the tested compounds should not be toxic and should show high intestinal absorption. CONCLUSIONS: New tricyclic 1,2-thiazine derivatives exert a neuroregenerative effect in the neuroinflammation model, presumably via their inhibitory influence on COX activity and reduction of oxidative and nitrosative stress.


Assuntos
Doença de Alzheimer , Neuroblastoma , Tiazinas , Humanos , Lipopolissacarídeos/toxicidade , Microglia , Receptor 4 Toll-Like/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo , Simulação de Acoplamento Molecular , Técnicas de Cocultura , Doenças Neuroinflamatórias , Donepezila/farmacologia , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Neuroblastoma/metabolismo , Anti-Inflamatórios/farmacologia , Tiazinas/efeitos adversos , Tiazinas/metabolismo
14.
Oxid Med Cell Longev ; 2022: 1504929, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35340213

RESUMO

Inflammatory diseases are a common therapeutic problem and nonsteroidal anti-inflammatory drugs are not deprived of side effects, of which ulcerogenic activity is one of the most frequent. The aim of the study was to evaluate the anti-inflammatory activity of the sanguinarine-chelerythrine (SC) fraction of Coptis chinensis and its influence on the integrity of gastric mucosa. The study was conducted on sixty male rats randomly divided into six experimental groups: two control groups (a negative control group CON and a positive control group CAR); three groups receiving an investigational fraction of C. chinensis (1, 5, 10 mg/kg i.g.) named SC1, SC5, and SC10, respectively; and a group receiving indomethacin (IND) (10 mg/kg i.g.) as a reference drug. In all animals, the carrageenan-induced paw oedema was measured; PGE2 release, TNFα production, and MMP-9 concentration in inflamed tissue were determined. Additionally, the macroscopic and microscopic damage of gastric mucosa was evaluated. Administration of SC dose-dependently inhibited the second phase of carrageenan rat paw oedema and PGE2 release, decreased the production of TNFα, and reduced the concentration of MMP-9, and the efficacy of the highest dose was comparable to the effect of IND. Contrary to IND, no gastrotoxic activity of SC was detected. The investigated sanguinarine-chelerythrine fraction of C. chinensis seems to be a promising candidate for further research on new anti-inflammatory and analgesic drugs characterized with a safer gastric profile compared to existing NSAIDs.


Assuntos
Coptis chinensis , Edema , Animais , Anti-Inflamatórios/efeitos adversos , Benzofenantridinas , Carragenina/toxicidade , Edema/induzido quimicamente , Edema/tratamento farmacológico , Isoquinolinas , Masculino , Ratos
15.
Nutrients ; 13(5)2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-34064936

RESUMO

Osteoporosis is a systemic bone disease characterized by reduced bone mass and the deterioration of bone microarchitecture leading to bone fragility and an increased risk of fractures. Conventional anti-osteoporotic pharmaceutics are effective in the treatment and prophylaxis of osteoporosis, however they are associated with various side effects that push many women into seeking botanicals as an alternative therapy. Traditional folk medicine is a rich source of bioactive compounds waiting for discovery and investigation that might be used in those patients, and therefore botanicals have recently received increasing attention. The aim of this review of literature is to present the comprehensive information about plant-derived compounds that might be used to maintain bone health in perimenopausal and postmenopausal females.


Assuntos
Medicina Herbária , Osteoporose Pós-Menopausa/terapia , Osteoporose/terapia , Animais , Densidade Óssea , Osso e Ossos , Botânica , Feminino , Fraturas Ósseas/tratamento farmacológico , Humanos , Fitoestrógenos/química , Fitoestrógenos/uso terapêutico
16.
Artigo em Inglês | MEDLINE | ID: mdl-33668937

RESUMO

The aim of the study was to determine the effects of short-term (4 weeks, twice a week: 8 sessions) plyometric training on agility, jump, and repeated sprint performance in female soccer players. The study comprised 17 females performing this sports discipline. The players were randomly divided into two groups: with plyometric training (PLY) and the control (CON). All players followed the same training program, but the PLY group also performed plyometric exercises. Tests used to evaluate physical performance were carried out immediately before and after PLY. After implementing the short PLY training, significant improvement in jump performance (squat jump: p = 0.04, ES = 0.48, countermovement jump: p = 0.009, ES = 0.42) and agility (p = 0.003, ES = 0.7) was noted in the PLY group. In the CON group, no significant (p > 0.05) changes in physical performance were observed. In contrast, PLY did not improve repeated sprint performance (p > 0.05) among female soccer players. In our research, it was shown that PLY can also be effective when performed for only 4 weeks instead of the 6-12 weeks typically applied.


Assuntos
Desempenho Atlético , Exercício Pliométrico , Corrida , Futebol , Feminino , Humanos , Força Muscular , Postura
17.
Nutrients ; 13(10)2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34684622

RESUMO

Cornelian cherry (Cornus mas L.) fruits possess potential cardiovascular, lipid-lowering and hypoglycemic bioactivities. The aim of this study is to evaluate the influence of resin-purified cornelian cherry extract rich in iridoids and anthocyanins on several transcription factors, intima/media ratio in aorta and serum parameters, which determine or are valuable indicators of the adverse changes observed in the course of atherosclerosis, cardiovascular disease, and metabolic syndrome. For this purpose, male New Zealand rabbits were fed a diet enriched in 1% cholesterol for 60 days. Additionally, one group received 10 mg/kg b.w. of cornelian cherry extract and the second group 50 mg/kg b.w. of cornelian cherry extract. PPAR-α and PPAR-γ expression in the aorta, LXR-α expression in the liver; cholesterol, triglycerides, adipokines, apolipoproteins, glucose and insulin levels in serum; the intima and media diameter in the thoracic and abdominal aorta were determined. Administration of cornelian cherry extract resulted in an enhancement in the expression of all tested transcription factors, a decrease in triglycerides, leptin and resistin, and an increase in adiponectin levels. In addition, a significant reduction in the I/M ratio was observed for both the thoracic and abdominal aorta. The results we have obtained confirm the potential contribution of cornelian cherry extract to mitigation of the risk of developing and the intensity of symptoms of obesity-related cardiovascular diseases and metabolic disorders such as atherosclerosis or metabolic syndrome.


Assuntos
Antocianinas/farmacologia , Doenças Cardiovasculares/prevenção & controle , Cornus/química , Iridoides/farmacologia , Síndrome Metabólica/prevenção & controle , Extratos Vegetais/farmacologia , Adipocinas/sangue , Animais , Aorta/metabolismo , Aterosclerose/metabolismo , Aterosclerose/prevenção & controle , Doenças Cardiovasculares/metabolismo , Colesterol na Dieta/efeitos adversos , Humanos , Fígado/metabolismo , Receptores X do Fígado/metabolismo , Masculino , Síndrome Metabólica/metabolismo , Obesidade/tratamento farmacológico , Obesidade/metabolismo , PPAR alfa/metabolismo , PPAR gama/metabolismo , Coelhos , Triglicerídeos/sangue
18.
Pharmaceuticals (Basel) ; 14(3)2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33652916

RESUMO

Cyclophosphamide (CPX) exerts toxicity in the urogenital system. The current study was designed to evaluate the effect of morin-5'-sulfonic acid sodium salt (NaMSA) on CPX-induced urogenital toxicity in rats. NaMSA (100 mg/kg/daily) and CPX (15 mg/kg/daily) alone or in combination and 0.9% NaCl (as a control) were given intragastrically for 10 days. Testes and epididymes from male and urinary bladders from male and female rats were evaluated histologically. In testes and epididymes, morphological changes and relative decrease in sperm count were assessed. In urinary bladders edema, hemorrhage and urothelium erosions were described by 0-2 points scoring system. Reproductive score (RS-in total 6 points) and urinary bladder score (BS-in total 6 points) were thereafter calculated. In CPX-receiving group RS (2.7) and BS (3.3) were significantly higher than in the control (0.5 and 0.25 for RS and BS, respectively). Co-administration of NaMSA reversed most of the morphological changes, which was reflected by lower RS and BS score (0.5 and 1.2 for RS and BS, respectively). The preliminary findings suggest that NaMSA may attenuate CPX-induced histological changes in rat urogenital tract.

19.
Oxid Med Cell Longev ; 2021: 5596090, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34373766

RESUMO

Highly active antiretroviral therapy (HAART) is used in HIV-infected patients. Alongside the prolongation of patients' life, adverse side effects associated with long-term therapy are becoming an increasing problem. Therefore, optimizing of HAART is extremely important. The study is aimed at evaluating the toxicity of abacavir and etravirine in monotherapy on the reproductive system, liver, kidneys, and bones in young, sexually mature, male rats. Thirty-six 8-week-old male Wistar rats randomized into three 12-animal groups received either normal saline (control), abacavir 60 mg/kg (AB group), or etravirine 40 mg/kg (ET group) once daily for 16 weeks. Semen morphology, oxide-redox state parameters (MDA, SOD, catalase, GPx, glutathione, GSH/GSSG ratio) in tissue homogenates (testes, liver, kidneys), and serum samples were studied. In bones, microcomputed tomography and a four-point bending test were performed. Total sperm count, sperm concentration, motility, and sperm morphology did not differ significantly in AB or ET groups compared to the control. In the flow cytometry of semen, an increased percentage of cells with denatured DNA was noticed for both tested drugs. However, no significant changes of oxide-redox state in testicular homogenates were found, except of increased SOD activity in the AB-receiving group. Additionally, ET significantly altered catalase and GPx in the liver and SOD activity in kidneys. Abacavir decreased catalase in the liver and GSH levels in kidneys. AB caused significant changes to bone microarchitecture (bone volume fraction, trabecular number, connectivity density, total porosity) and increased Young's modulus. Etravirine had a greater impact on macrometric parameters of bones (tibial index, mid-tibial diameter, femur length). After 4 weeks in the ET group, a lower 1,25-dihydroxyvitamin D3 serum concentration was found. The results showed that abacavir and etravirine disturb oxidative stress. An increase in the percentage of sperms with chromatin damage suggests decreased fertility in rats receiving the studied drugs. Both drugs affected bone formation in growing rats. Additionally, etravirine disturbed vitamin D metabolism.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Densidade Óssea/efeitos dos fármacos , Didesoxinucleosídeos/efeitos adversos , Nitrilas/efeitos adversos , Estresse Oxidativo , Pirimidinas/efeitos adversos , Sêmen/efeitos dos fármacos , Animais , Fármacos Anti-HIV/administração & dosagem , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Catalase/metabolismo , Didesoxinucleosídeos/administração & dosagem , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Rim/efeitos dos fármacos , Rim/crescimento & desenvolvimento , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/crescimento & desenvolvimento , Fígado/metabolismo , Masculino , Malondialdeído/metabolismo , Nitrilas/administração & dosagem , Pirimidinas/administração & dosagem , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Testículo/efeitos dos fármacos , Testículo/crescimento & desenvolvimento , Testículo/metabolismo
20.
Oxid Med Cell Longev ; 2020: 2735790, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32318236

RESUMO

The old adage says, "you are what you eat." And although it is a banality repeated by many with a grain of salt, it also has quite a bit of truth in it, as the products we eat have a considerable impact on our health. Unfortunately, humanity is eating worse from one year to another, both in terms of product quality and eating habits. At the same time, it is brought up frequently that plant products should form the basis of our diet. This issue was also reflected in the new version of the food pyramid. Iridoids and anthocyanins are groups of plant compounds with proven beneficial effects on health. Both groups affect the cardiovascular system and the liver functions. Although many mechanisms of action and the therapeutic effects of these compounds have already been learned, intensive animal and clinical research is still underway to explore their new curative mechanisms and effects or to broaden our knowledge of those previously described. In this article, we review the effects of natural iridoids and anthocyanins on selected parameters of liver and cardiovascular system functions.


Assuntos
Antocianinas/uso terapêutico , Sistema Cardiovascular/efeitos dos fármacos , Iridoides/uso terapêutico , Fígado/efeitos dos fármacos , Antocianinas/farmacologia , Humanos , Iridoides/farmacologia
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