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1.
Antioxidants (Basel) ; 13(4)2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38671840

RESUMO

Oxidative stress represents the pathophysiological basis for most disorders, including reproductive issues. Polycystic ovary syndrome (PCOS) is heterogeneous endocrine disorder of women characterized primarily by irregular menstrual cycles, hyper-androgenism, and ovulatory dysfunction. In the last decades, PCOS was recognized as a systemic silent inflammation and an oxidative disturbance-related disorder, exerting multifaceted symptoms, including metabolic. PCOS treatment should involve a personalized approach tailored to individual symptoms; however, the results are often unsatisfactory. Various supplementary treatments have been proposed to assist in the management and alleviation of PCOS symptoms. Cinnamon and ginger, known for millennia as herbs used in spices or traditional medicine for the treatment of various diseases, are of interest in this study. The aim of this study is to evaluate and investigate the effects of cinnamon and ginger in PCOS patients. Using relevant keywords we searched through PubMed/MEDLINE, Science Direct, Google Scholar and Web of science to find animal studies, pre-clinical, and clinical studies which were then reviewed for usage. Out of all of the reviewed studies a total of 65 studies were included in this review article. Cinnamon and ginger can affect hormonal status, lipid profile, obesity, and insulin resistance by mitigating oxidative stress and inflammation. Generally, based on current clinical evidence, it was revealed that supplementation with cinnamon or ginger had a useful impact in patients with PCOS. This review summarizes the antioxidative effects of ginger and cinnamon in PCOS treatment, highlighting their potential benefits in other oxidative stress-related pathologies.

2.
Medicina (Kaunas) ; 59(6)2023 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-37374308

RESUMO

Background and Objectives: Polycystic ovary syndrome (PCOS) is a frequent multifactorial endocrinopathy affecting women in the reproductive period, often associated with infertility and metabolic disorders. The use of animal models helps to better understand etiopathogenesis, enabling the examination of the effects of certain drugs in order to discover the best possible therapeutic approach. We tried to investigate the additional effect of estradiol-valerate (EV) and high-fat diet (HFD) in female rats to explore PCOS-related alterations with special focus on oxidative stress. Materials and Methods: Animals were divided into three groups: control group (CTRL, n = 6), estradiol-valerate group (EV, n = 6), and estradiol-valerate group on HFD (EV + HFD, n = 6). PCOS was induced by single subcutaneous injection of long-acting EV in a dose of 4 mg/per rat. We tried to improve the metabolic characteristics of the PCOS animal model by adding HFD, so the CTRL and EV group had a regular diet, while the EV + HFD group had HFD during the induction period of 60 days. Results: We observed alterations of anthropometric parameters and hormonal disturbances, along with estrus cycle impairment reassembly to obese-type PCOS phenotype. Moreover, glucose metabolism was impaired after addition of HFD to EV protocol, contrary to EV administered alone. Histological analysis confirmed more numerous cystic follicles after the combination of EV and HFD protocol. The alterations of oxidative stress markers could be related to and serve as the mechanistic base for development of PCOS-related endocrine, reproductive, and metabolic properties. Conclusions: The additive effect of EV and HFD was obvious in the majority of the parameters observed. Our study strongly demonstrated metabolic as well as reproductive properties of PCOS in rats.


Assuntos
Síndrome do Ovário Policístico , Ratos , Feminino , Animais , Humanos , Síndrome do Ovário Policístico/metabolismo , Dieta Hiperlipídica/efeitos adversos , Estradiol/efeitos adversos , Reprodução , Estresse Oxidativo , Valeratos/efeitos adversos
3.
Univers Access Inf Soc ; : 1-14, 2023 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-37361671

RESUMO

This study offers a comprehensive analysis of COVID-19 research in education. A multi-methods approach was used to capture the full breadth of educational research. As such, a bibliometric analysis, structural topic modeling, and qualitative synthesis of top papers were combined. A total of 4,201 articles were retrieved from Scopus, mostly published from 2019 to 2021. In this work special attention is paid to analyzing and synthesizing findings about: (i) status of research about COVID-19 regarding frequencies, venues, publishing countries, (ii) identification of main topics in the COVID-19 research, and (iii) identification of the major themes in most cited articles and their impact on the educational community. Structural topic modeling identified three main groups of topics that related to education in general, moving to online education, or diverse topics (e.g., perceptions, inclusion, medical education, engagement and motivation, well-being, and equality). A deeper analysis of the papers that received most attention revealed that problem understanding was the dominating theme of papers, followed by challenges, impact, guidance, online migration, and tools and resources. A vast number of papers were produced. However, thoughtful, well-planned, and meaningful research was hard to conceptualize or implement, and a sense of urgency led to a deluge of research with thin contributions in a time of dire need to genuine insights.

4.
Biomedicines ; 11(4)2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-37189616

RESUMO

Polycystic ovary syndrome (PCOS) is the most frequent endocrinopathy during women's reproductive age. PCOS is a heterogeneous disorder featuring specific cardiometabolic properties. The association between the presence of metabolic disorders and PCOS supports the claim that the regulation of glycemic status is very important in these patients. There is a wide range of therapeutic options (including those treating diabetes mellitus type 2) with potential advantages available for the management of PCOS. Sodium-glucose cotransporter type 2 inhibitors (SGLT-2is) improve glucose metabolism, reduce fat tissue, lower blood pressure, reduce oxidative stress and inflammation, and protect the cardiovascular system. Currently, the use of SGLT-2is is not widespread in PCOS therapy, although these drugs represent a promising new therapeutic approach. Therefore, it is necessary to initiate further study in order to determine more effective therapies for PCOS and investigate the effect of SGLT-2is, both as a monotherapy and in combination with other drugs. It is necessary to understand the mechanisms underlying SGLT-2is in PCOS and their effects on long-term complications, especially since the gold standard treatment for PCOS, such as metformin and oral contraceptives, do not have long-term cardioprotective effects. The effects of SGLT-2is seem to involve cardiac protection, while diminishing endocrine and reproductive abnormalities in PCOS. In the current narrative review, we examine the most recent clinical evidence and discuss the potential applications of SGLT-2is for PCOS therapy.

5.
J Clin Med ; 11(21)2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36362749

RESUMO

The inflammatory processes that occur at the maternal−fetal interface are considered one of the factors that are responsible for preterm birth. The pro-inflammatory roles of the Gal-3-induced activation of NLRP3 inflammasome and the consecutive production of IL-1ß have been described in several acute and chronic inflammatory diseases, but the role of this inflammatory axis in parturition has not been studied. The aim of this study was to analyze the protein expression of Gal-3, NLRP3, and IL-1ß in the decidua, villi, and fetal membranes, and to analyze their mutual correlation and correlation with the clinical parameters of inflammation in preterm birth (PTB) and term birth (TB). The study included 40 women that underwent a preterm birth (gestational age of 25.0−36.6) and histological chorioamnionitis (PTB) and control subjects, 22 women that underwent a term birth (gestational age of 37.0−41.6) without histological chorioamnionitis (TB). An analysis of the tissue sections that were stained with anti- Gal-3, -NLRP3, and -IL-1ß antibodies was assessed by three independent investigators. The expression levels of Gal-3 and IL-1ß were significantly higher (p < 0.001) in the decidua, villi, and fetal membranes in the PTB group when they compared to those of the TB group, while there was no difference in the expression of NLRP3. A further analysis revealed that there was no correlation between the protein expression of NLRP3 and the expression of Gal-3 and IL-1ß, but there was a correlation between the expression of Gal-3 and IL-1ß in decidua (R = 0.401; p = 0.008), villi (R = 0.301; p = 0.042) and the fetal membranes (R = 0.428; p = 0.002) in both of the groups, PTB and TB. In addition, the expression of Gal-3 and IL-1ß in decidua and the fetal membranes was in correlation with the parameters of inflammation in the maternal and fetal blood (C-reactive protein, leukocyte number, and fibrinogen). The strong correlation between the expression of Gal-3 and IL-1ß in the placental and fetal tissues during labor indicates that Gal-3 may participate in the regulation of the inflammatory processes in the placenta, leading to increased production of IL-1ß, a cytokine that plays the main role in both term and preterm birth.

6.
Life (Basel) ; 12(8)2022 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-36013421

RESUMO

(1) Background: The aim of this study was to show the effects of swimming and nandrolone administration on cardiodynamic and morphometric parameters of the isolated rat heart. (2) The study included 72 Wistar rats, divided into three groups, scheduled to be sacrificed after the second, third, and fourth week. Each group was divided into four subgroups: control (T-N-), nandrolone (T-N+), swimming training (T+N-), and swimming training plus nandrolone (T+N+) group. The rats from T+N- and T+N+ swam 1 h/day, 5 days/week while ones from T-N+ and T+N+ received weekly nandrolone decanoate (20 mg/kg). The isolated hearts were perfused according to the Langendorff technique and measured parameters: dp/dt max/min, SLVP, DLVP, heart rate, and coronary flow. Hearts were fixed and stained with H/E and Masson trichrome dyes. (3) dp/dt max and dp/dt min were increased in the T-N+ group at higher perfusion pressure compared to the T-N- group. SLVP and DLVP were increased in all groups after the 4th week. Collagen content was increased in T-N+ by 403% and in T+N+ by 357% groups, while it was decreased in T+N- compared to the control after 4th week. (4) Conclusions: Nandrolone alone or combined with swimming had a deleterious effect on myocardial function and perfusion.

7.
Antioxidants (Basel) ; 11(6)2022 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-35739998

RESUMO

Polycystic ovary syndrome (PCOS) represents the most common endocrinopathy among childbearing-age women, with oxidative stress (OS) underlying its etiopathogenesis. Metformin (MET) represents a frequently used agent in PCOS. However, weak results encourage alternative treatments. We aimed to investigate isolated and synergistic effects of Standardized Aronia melanocarpa extract (SEA) and MET for alleviating reproductive and metabolic PCOS abnormalities. PCOS induction was followed by 28-day treatment with MET, SAE, or MET + SEA. Bodyweight (BW), cyclicity, histological, and ultrasonographical ovarian analyses were performed. Hormonal, glycemic, and lipid profiles were accessed, as well as systemic and ovarian oxidative status; BW, cyclicity, ovarian histomorphology, ovarian volume, testosterone and progesterone levels, as well as LDL, triglycerides, and total cholesterol levels were aggravated after PCOS-induction and improved after MET, SEA, and MET + SEA treatment. MET + SEA had the greatest impact on glycoregulation. Alterations in OS parameters (TBARS, O2-, H2O2, catalase, superoxide dismutase, and reduced glutathione) could be responsible for observed differences; (4) Conclusions: Our findings confirmed that SAE alone or along with MET was capable of ameliorating reproductive and metabolic disturbances in the PCOS rat model, with the restoration of OS parameters. SAE alone did not alter the protective effects of MET in PCOS.

8.
Oxid Med Cell Longev ; 2022: 9598211, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35464768

RESUMO

Oxidative stress (OS) is considered a significant risk factor for the development of anemia in patients treated by regular hemodialysis (HD). Moreover, OS represents a risk factor for the development of erythropoietin (EPO) resistance in these patients. The aim of this study was to examine the role of OS regarding EPO resistance development in patients treated by regular HD. 96 patients treated with standard HD and on-line hemodiafiltration were included in this study. The patients were treated with short-acting and long-acting EPOs for anemia. The concentration of superoxide anion radical, hydrogen peroxide, thiobarbituric acid reactive substances, and nitric oxide in the form of nitrites and the activity of catalase, superoxide dismutase and reduced glutathione were measured in patients' blood spectrophotometrically. Standard biochemical analysis, inflammatory markers, nutritional status, HD parameters, and erythropoietin resistance index were also determined. Patients with resistance to short-acting EPO had significantly lower concentration of hemoglobin in the blood and hematocrit value, a significantly higher serum ferritin concentration, and significantly lower catalase activity in erythrocytes than patients without EPO resistance. Patients with resistance to long-acting EPO have a significantly lower hemoglobin concentration in the blood, hematocrit values, and serum concentration of prealbumin and vitamin D, as well as significantly higher concentration of C-reactive protein, superoxide anion, and hydrogen peroxide concentration than those without resistance. OS significantly contributes to EPO resistance development. OS, higher ferritin and CRP levels, lower hemoglobin, hematocrit and prealbumin levels, and vitamin D deficiency represent significant risk factors for EPO resistance development in HD patients.


Assuntos
Anemia , Eritropoetina , Falência Renal Crônica , Anemia/etiologia , Proteína C-Reativa/metabolismo , Catalase/metabolismo , Feminino , Ferritinas/metabolismo , Hemoglobinas/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Masculino , Estresse Oxidativo , Pré-Albumina/metabolismo , Proteínas Recombinantes/metabolismo , Diálise Renal/efeitos adversos , Superóxidos/metabolismo
9.
Heart Fail Rev ; 27(3): 935-949, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-33534040

RESUMO

This paper highlights the cardioprotective potential of sodium-glucose cotransporter 2 inhibitors (SLGT2i), as well as several most discussed mechanisms responsible for their cardioprotection. Cardiovascular diseases are considered a primary cause of death in nearly 80% of type 2 diabetes mellitus (T2DM) patients, with a 2-4-fold greater incidence of heart failure (HF) among diabetics. As novel hypoglycemics, SGLT2i showed exceptional cardiovascular benefits, reflected through robust reductions of cardiovascular mortality and hospitalization for HF in T2DM patients. Recently, those effects have been reported even in patients with HF and reduced ejection fraction irrespectively of diabetic status, suggesting that cardioprotective effects of SGLT2i are driven independently of their hypoglycemic actions. SGLT2i exerted hemodynamic and metabolic effects, partially driven by natriuresis and osmotic diuresis. However, those systemic effects are modest, and therefore cannot be completely related to the cardiac benefits of these agents in T2DM patients. Hence, increased circulating ketone levels during SGLT2i administration have brought out another hypothesis of a cardiac metabolic switch. Moreover, SGLT2i influence ion homeostasis and exert anti-inflammatory and antifibrotic effects. Their enviable influence on oxidative stress markers, as well as anti- and pro-apoptotic factors, have also been reported. However, since the main mechanistical contributor of their cardioprotection has not been elucidated yet, a joint action of systemic and molecular mechanisms has been suggested. In the light of ongoing trials evaluating the effects of SGLT2i in patients with HF and preserved ejection fraction, a new chapter of beneficial SGLT2i mechanisms is expected, which might resolve their main underlying action.


Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Volume Sistólico
10.
Reproduction ; 163(1): 11-21, 2021 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-34762597

RESUMO

Numerous evidence implies complex interrelations between polycystic ovary syndrome (PCOS) and hypertension (HT) in reproductive-age women. In this study, we aimed to investigate the potential strain differences in ovarian morphology, hemodynamic, and biochemical characteristics in an androgen-induced PCOS rat model. A total of 24 rats of 3 weeks old (12 Wistar Kyoto - WK and 12 spontaneously hypertensive rats - SHR) were divided into four groups: WK, WK PCOS, SHR, and SHR PCOS. PCOS was induced by daily s.c. injections of testosterone enanthate (1 mg/100 g body weight) administered for 5 weeks. PCOS induction led to estrus cyclicity cessation, cystic ovarian appearance, and sex hormones disturbances in both strains. The morphometric parameters in ovaries were altered in a manner of PCOS-related changes in both strains (higher number in preantral, atretic, and cystic follicles). Ultrasonographically, a significant decrease in ovarian volume (OV) was registered in PCOS groups but also in SHR compared to WK rats. All blood pressure parameters were higher in SHR compared to WK. PCOS modeling increased systolic, mean arterial, and pulse pressure in WK strain, while in SHR, only mean arterial and pulse pressure were higher. Alterations in oxidative stress parameters could provide a molecular basis for PCOS-related changes: in PCOS groups, thiobarbituric acid reactive substance and superoxide anion radical levels were higher in both strains, while superoxide dismutase and glutathione were significantly lowered.


Assuntos
Hipertensão , Síndrome do Ovário Policístico , Animais , Pressão Sanguínea , Modelos Animais de Doenças , Feminino , Humanos , Hipertensão/etiologia , Estresse Oxidativo/fisiologia , Síndrome do Ovário Policístico/induzido quimicamente , Ratos , Ratos Endogâmicos SHR
11.
Oxid Med Cell Longev ; 2021: 8862878, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512871

RESUMO

Polycystic ovary syndrome (PCOS) is a multifaced reproductive endocrinopathy affecting 6-20% of women of childbearing age. It was previously shown that women with PCOS have an increased risk of cardiovascular (CV) diseases. The aim of this study was to evaluate the cardiodynamic parameters of isolated rats' hearts, blood pressure levels, and histomorphological changes in the heart tissue following the androgen-induced PCOS model in rats and the role of oxidative stress in the development of these CV properties of PCOS. 21-day-old female rats (n = 12) were divided into control and PCOS groups. PCOS was induced by administration of testosterone enanthate (1 mg/kg BW, daily) during 35 days. During the autoregulation protocol (40-120 mmHg) on the Langendorff apparatus, ex vivo cardiodynamic parameters of retrogradely perfused hearts showed enhanced contractile function and increased lusitropic effects in the left ventricle (LV) in PCOS rats. Systolic and diastolic pressures in LV were elevated at all perfusion pressure values. Systemic arterial systolic blood pressure showed borderline elevation, while mean arterial blood pressure was significantly higher in PCOS rats. Histological evaluation of heart tissue depicted hypertrophic (8.3%) alterations in LV cardiomyocytes and increase (7.3%) in LV wall thickness. Oxidative stress parameters were altered in systemic circulation, coronary venous effluent (CVE), and heart tissue. Levels of superoxide dismutase and reduced glutathione were decreased in blood and heart tissue, while catalase activity was not altered. Degree of lipid peroxidation was increased in circulation as well as heart tissue. Increased levels of O2 - in CVE indicated the cardiotoxic effects in the rat PCOS model. The mentioned alterations of oxidative stress parameters in the blood, CVE, and heart could be recommended as potential contributors underlying the development of CV risk in PCOS women.


Assuntos
Doenças Cardiovasculares/fisiopatologia , Estresse Oxidativo/fisiologia , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/metabolismo , Testosterona/análogos & derivados , Animais , Modelos Animais de Doenças , Feminino , Humanos , Síndrome do Ovário Policístico/patologia , Ratos , Ratos Wistar , Testosterona/administração & dosagem
12.
Basic Clin Androl ; 31(1): 17, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34261436

RESUMO

BACKGROUND: During the last decades, the abuse of anabolic androgenic steroids (AASs) has become popular among professional and recreational athletes. The abuse of AASs leads to decreased levels of sex hormones, but the available literature a gives very small pool of data regarding the effects of swimming alone or combined with AASs on testicle tissue. The aim of this study was to investigate the effects of four-week administration of nandrolone decanoate and swimming training alone or in combination on morphometric parameters, androgen receptor (AR) and redox state in testicle tissue. The study included Wistar albino male rats, 10 weeks old, classified into 4 groups: control (T-N-), nandrolone (T-N+), swimming training (T+N-) and swimming training with nandrolone (T+N+). The rats from nandrolone (N+) groups received nandrolone decanoate 20 mg/kg b.w.once per week. The rats from training (T+) groups, swam 1 h/day 5 days/week. The isolated testicles were measured, left testicles were routinely processed for histological analysis, while right testicles were homogenized and prepared for the analysis of the following oxidative stress biomarkers: index of lipid peroxidation (TBARS), nitrites, catalase, superoxide dismutase (SOD), and reduced glutathione (GSH). RESULTS: Diameter, as well as cross-section area of seminiferous tubules were decreased by 10 % and 21 % (respectively) in the T-N+ group and by 15% and 41 % (respectively) in the T+N+ group compared to control. Interstitium of the testicles was decreased in all experimental groups. Reduction of immunoreactivity of AR in T-N+ group was 22 %, in T+N+ group was 9 % compared to control. TBARS levels were increased in T+N- and T+N+ groups. Nitrites were decreased in T+N+ group. Catalase activity was increased in all experimental groups. Swimming alone or combined with nandrolone decreased the level of GSH compared to control. SOD activity was decreased in T-N+ and T+N+ groups compared to control. CONCLUSIONS: Nandrolone alone or combined with swimming decreased morphometric parameters and amount of AR in testicle tissue. Changes in the redox state indicate reproductive dysfunction.


RéSUMé: CONTEXTE: Au cours des dernières décennies, l'abus de stéroïdes androgéniques anabolisants (SAA) est devenu populaire parmi les athlètes professionnels et récréatifs. L'abus des SAA conduit à une diminution des niveaux d'hormones sexuelles, mais la littérature sur les effets de la natation seule ou combinée avec des SAA sur les tissus testiculaires est encore très limité. Le but de cette étude était d'étudier les effets de l'administration de quatre semaines de décanoate de nandrolone et de l'entraînement à la natation seuls ou en combinaison sur les paramètres morphométriques, le récepteur aux androgènes (RA) et l'état redox dans le tissu testiculaire. L'étude a inclus des rats mâles Wistar albinos, âgés de 10 semaines, classés en 4 groupes: contrôle (T-N-), nandrolone (T-N+), entraînement à la natation (T+N-) et entraînement à la natation avec nandrolone (T+N+). Les rats des groupes nandrolone (N+) ont reçu du décanoate de nandrolone 20 mg/kg p.c. une fois par semaine. Les rats des groupes entraînement (T+) nageaient 1 h/jour 5 jours/semaine. Les testicules isolés ont été mesurés, les testicules gauches ont été systématiquement traités pour l'analyse histologique tandis que les testicules droits ont été homogénéisés et préparés pour l'analyse des biomarqueurs de stress oxydatif suivants: indice de peroxydation lipidique (TBARS), nitrites, catalase, superoxyde dismutase (SOD) et glutathion réduit (GSH). RéSULTATS: Le diamètre, ainsi que la section transversale des tubules séminifères ont été réduits de 10 % et 21 % (respectivement) dans le groupe T-N+ et de 15 % et 41 % (respectivement) dans le groupe T+N+ par rapport au groupe témoin. L'interstitium des testicules était diminué dans tous les groupes expérimentaux. La réduction de l'immunoréactivité de RA dans le groupe T-N+ était de 22 %, dans le groupe T+N+ était de 9 % par rapport au groupe témoin. Les niveaux de TBARS ont augmenté dans les groupes T+N- et T+N+. Les nitrites ont diminué dans le groupe T+N+. L'activité de la catalase a été augmentée dans tous les groupes expérimentaux. La natation seule ou combinée à la nandrolone a réduit le niveau de GSH par rapport au contrôle. L'activité de la SOD était diminuée dans les groupes T-N+ et T+N+ par rapport au contrôle. CONCLUSIONS: La nandrolone seule ou combinée à la natation a diminué les paramètres morphométriques et la quantité de RA dans le tissu testiculaire. Les changements de l'état redox indiquent un dysfonctionnement de la reproduction.

13.
Pharmacol Res ; 160: 105188, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32919041

RESUMO

There has always been a keen interest of basic and clinical researchers to search for cancer therapeutics having minimum off-target effects and maximum anticancer activities. In accordance with this approach, there has been an explosion in the field of natural products research in the past few decades because of extra-ordinary list of natural extracts and their biologically and pharmacologically active constituents having significant medicinal properties. Apparently, luteolin-mediated anticancer effects have been investigated in different cancers but there is superfluousness of superficial data. Generalized scientific evidence encompassing apoptosis, DNA damage and anti-inflammatory effects has been reported extensively. However, how luteolin modulates deregulated oncogenic pathways in different cancers has not been comprehensively uncovered. In this review we have attempted to focus on cutting-edge research which has unveiled remarkable abilities of luteolin to modulate deregulated oncogenic pathways in different cancers. We have partitioned the review into various sections to separately discuss advancements in therapeutic targeting of oncogenic protein networks. We have provided detailed mechanistic insights related to JAK-STAT signaling and summarized how luteolin inhibited STAT proteins to inhibit STAT-driven gene network. We have also individually analyzed Wnt/ß-catenin and NOTCH pathway and how luteolin effectively targeted these pathways. Mapping of the signaling landscape has revealed that NOTCH pathway can be targeted therapeutically. NOTCH pathway was noted to be targeted by luteolin. We have also conceptually analyzed how luteolin restored TRAIL-induced apoptosis in resistant cancers. Luteolin induced an increase in pro-apoptotic proteins and efficiently inhibited anti-apoptotic proteins to induce apoptosis. Luteolin mediated regulation of non-coding RNAs is an exciting and emerging facet. Excitingly, there is sequential and systematic accumulation of clues which have started to shed light on intricate regulation of microRNAs by luteolin in different cancers. Collectively, sophisticated information will enable us to develop a refined understanding of the multi-layered regulation of signaling pathways and non-coding RNAs by luteolin in different cancers.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Luteolina/farmacologia , MicroRNAs/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Animais , Antineoplásicos Fitogênicos/uso terapêutico , Apoptose/efeitos dos fármacos , Marcação de Genes , Humanos , Luteolina/uso terapêutico , Receptores Notch/efeitos dos fármacos , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/efeitos dos fármacos , Fatores de Transcrição STAT/efeitos dos fármacos , Serina-Treonina Quinases TOR/efeitos dos fármacos
14.
Biomolecules ; 9(12)2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31861240

RESUMO

Since cisplatin therapy is usually accompanied with numerous toxicities, including neurotoxicity, that involve tissue oxidative damage, the aim of this study was to evaluate the possible protective effect of N-acetylcysteine (NAC) on the anxiogenic response to cisplatin (CIS). Thirty-two male Wistar albino rats divided into four groups (control, cisplatin, NAC, and CIS + NAC). All treatments were delivered intraperitoneally. On day one, the control and cisplatin groups received saline while the NAC and CIS + NAC groups were administered with NAC (500 mg/kg). On the fifth day, the control group received saline while the CIS group was treated with cisplatin (7.5 mg/kg), the NAC group again received NAC (500 mg/kg), and the CIS + NAC group was simultaneously treated with cisplatin and NAC (7.5 and 500 mg/kg, respectively). Behavioral testing, performed on the tenth day in the open field (OF) and elevated plus maze (EPM) tests, revealed the anxiogenic effect of cisplatin that was significantly attenuated by NAC. The hippocampal sections evaluation showed increased oxidative stress (increased lipid peroxidation and decline in antioxidant enzymes activity) and proapoptotic action (predominantly by diminished antiapoptotic gene expression) following a single dose of cisplatin. NAC supplementation along with cisplatin administration reversed the prooxidative and proapoptotic effects of cisplatin. In conclusion, the results obtained in this study confirmed that antioxidant supplementation with NAC may attenuate the cisplatin-induced anxiety. The mechanism of anxiolytic effect achieved by NAC may include the decline in oxidative damage that down regulates increased apoptosis and reverses the anxiogenic action of cisplatin.


Assuntos
Acetilcisteína/farmacologia , Ansiolíticos/farmacologia , Ansiedade/induzido quimicamente , Ansiedade/tratamento farmacológico , Cisplatino/efeitos adversos , Substâncias Protetoras/farmacologia , Acetilcisteína/administração & dosagem , Acetilcisteína/química , Animais , Ansiolíticos/administração & dosagem , Ansiolíticos/química , Antineoplásicos/administração & dosagem , Antioxidantes/administração & dosagem , Comportamento Animal/efeitos dos fármacos , Cisplatino/administração & dosagem , Masculino , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/química , Ratos , Ratos Wistar
15.
Neuromodulation ; 18(8): 736-43, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25917248

RESUMO

OBJECTIVE: The goal of this study is to minimize arm forces applied during sit-to-stand (STS) transfers in persons with spinal cord injury (SCI) by using functional electrical stimulation (FES) applied to lower limbs muscles. MATERIALS AND METHODS: A new FES system has been used to automatically trigger muscle stimulation of the lower limbs, at the desired moment in regards to trunk motion. The objective was to decrease arm participation during STS motion of a person with complete paraplegia and low-level tetraplegia. Six participants with chronic SCI participated in the study. Participants with SCI were recruited to complete STS movement using a new system for FES-assisted STS transfer. All participants attended one muscle mapping session to test their muscles condition, two training sessions to become familiarized with the experimental setup, and two measurement sessions using the proposed system for FES-assisted STS movement. The applied arm forces during STS movement were recorded and analyzed for different stimulation onset values with respect to the maximal trunk acceleration signal using one-way ANOVA statistical test. Post-hoc analysis was performed using Tukey's method. RESULTS: The results of this study showed that the moment of the stimulation onset has an influence on the arm forces applied during the STS motion. The lowest values of arm forces were obtained for STS movements where the electrical stimulation was triggered before and around the time corresponding to the maximal value of the trunk acceleration signal. CONCLUSION: Lowest arm forces values were obtained for STS motions that were similar to those of healthy persons in terms of trunk movements and beginning of lower limb movements in regards to maximal trunk acceleration signal. The FES system was able to mimic the rising motion of a healthy individual by triggering the FES at the appropriate moment. This method could prove useful for pivot transfer, therapeutic or functional verticalization.


Assuntos
Braço/fisiopatologia , Estimulação Elétrica/métodos , Extremidade Inferior/patologia , Músculo Esquelético/fisiologia , Traumatismos da Medula Espinal/fisiopatologia , Tronco/fisiopatologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transferência de Pacientes , Estudos Prospectivos , Adulto Jovem
16.
Planta Med ; 80(18): 1698-705, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25317772

RESUMO

In this paper, the chemical composition and biological activity of the essential oil of Artemisia absinthium was studied. The aim of this study was to investigate the potential of ethnopharmacological uses of this plant species in the treatment of gastrointestinal diseases and wounds, and as an insect repellent. The aerial part of the plant was hydrodistilled, and the chemical composition of the essential oil was analyzed by gas chromatography and gas chromatography/mass spectrometry. Forty-seven compounds, corresponding to 94.65 % of the total oil, were identified, with the main constituents being sabinene (24.49 %), sabinyl acetate (13.64 %), and α-phellandrene (10.29 %). The oil yield was 0.23 % (v/w). The antimicrobial activity of the oil was investigated against ten bacterial isolates (from patients wounds and stools) and seven American Type Culture Collection strains using a microwell dilution assay. The minimal inhibitory/bactericidal concentration of the oil ranged from < 0.08 to 2.43 mg/mL and from 0.08 to 38.80 mg/mL, respectively. The antioxidant activity of the essential oil was evaluated using 2,2-diphenyl-1-picrylhydrazil and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) radical-scavenging methods and assessed as significant. Skin irritation potential and acute toxicity of the oil were also investigated. Results of the skin irritant reaction showed that none of the 30 volunteers developed a positive skin irritant reaction to undiluted A. absinthium essential oil. Acute oral exposure to the essential oil did not cause mortality in the treated mice, but it did cause neurological, muscle, and gastrointestinal problems. A subchronic toxicity test on Drosophila melanogaster showed that the essential oil of A. absinthium is toxic for developing insect larvae. Starting with the concentration of 0.38 % of essential oil in medium, significant mortality of larvae exposed to the oil was noted when compared to the control. Probit analysis revealed that the LC50 value of A. absinthium essential oil for D. melanogaster larvae after 15 days of exposure was 6.31 % (49 mg/mL). The essential oil also affected the development of D. melanogaster larvae and significantly delayed achievement of the pupa stadium.


Assuntos
Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Artemisia absinthium/química , Repelentes de Insetos/farmacologia , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Adolescente , Adulto , Animais , Anti-Infecciosos/química , Antioxidantes/química , Relação Dose-Resposta a Droga , Drosophila melanogaster/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos/métodos , Fezes/microbiologia , Feminino , Humanos , Repelentes de Insetos/química , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Óleos Voláteis/efeitos adversos , Plantas Medicinais/química , Sérvia , Testes de Irritação da Pele/métodos , Testes de Toxicidade Aguda , Testes de Toxicidade Subcrônica , Adulto Jovem
17.
J Neuroeng Rehabil ; 11: 118, 2014 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-25108539

RESUMO

BACKGROUND: Walking impairment after stroke can be addressed with the use of drop foot stimulators (DFS). Many studies have demonstrated that DFS improves walking speed, reduces spasticity and reduces the physiologic effort of walking. Current DFS, through activation of the common peroneal nerve, elicit ankle dorsiflexion during swing phase of gait. DFS are generally piloted by force sensing resistor placed in the shoe of the affected side with stimulation triggered ON by heel rise and triggered OFF by heel strike. A tilt sensor can also be used with stimulation triggered by the tilt of the shank of the affected leg. These triggering approaches are the standard for initiating stimulation. However, the real-time modulation of FES intensity to provide more optimized delivery of stimulation and also to regulate dorsiflexion in the presence of disturbances, such as fatigue and spasticity may increase the number of potential users of DFS. Concerning research domain, stimulators that would allow modulating the stimulation pattern in between heel rise and strike events would allow exploring new stimulation strategies. We propose to extract continuous information: the gait cycle index (GCI), from one inertial measurement unit (IMU) measuring shank tilt angle. In order to illustrate the use of this real-time information, we show the feasibility of piloting an electrical stimulator. METHODS: 12 subjects with post-stroke hemiplegia participated. A wireless IMU was placed on the unaffected shank and was used to estimate GCI. Subjects performed 3 trials in each of the 3 conditions: C1 no stimulation aid, C2 electrical stimulation assistance triggered by heel switch, C3 electrical stimulation assistance triggered from GCI. RESULTS: 1) the proposed algorithm was able to real-time estimate GCI, 2) events could be extracted from GCI information in order to trig a DFS. CONCLUSION: The estimation of the continuous GCI in individuals with stroke is possible. Events can be extracted from this information in order to trig a stimulator. These results are a first step towards the possibility to investigate new DFS paradigms based on real-time modulation of stimulation parameters.


Assuntos
Algoritmos , Terapia por Estimulação Elétrica/instrumentação , Terapia por Estimulação Elétrica/métodos , Transtornos Neurológicos da Marcha/fisiopatologia , Reabilitação do Acidente Vascular Cerebral , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
Nat Prod Commun ; 9(2): 281-6, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24689311

RESUMO

The chemical composition and antibacterial activity were examined of Libanotis montana Crantz subsp. leiocarpa (Heuff.) Soó. (Apiaceae) essential oil. Gas chromatography and gas chromatography/mass spectrometry were used to analyze the chemical composition of the oil. The antibacterial activity was investigated by the broth microdilution method against thirteen bacterial strains. The interactions of the essential oil and three standard antibiotics: tetracycline, streptomycin and chloramphenicol toward five selected strains were evaluated using the microdilution checkerboard assay in combination with chemometric methods: principal components analysis and hierarchical cluster analysis. Sesquiterpene hydrocarbons were the most abundant compound class in the oil (67.2%), with beta-elemene (40.4%) as the major compound. The essential oil exhibited slight antibacterial activity against the tested bacterial strains in vitro, but the combinations L. montana oil-chloramphenicol and L. montana oil-tetracycline exhibited mostly either synergistic or additive interactions. These combinations reduced the minimum effective dose of the antibiotics and, consequently, minimized their adverse side effects. In contrast, the association of L. montana essential oil and streptomycin was characterized by strong antagonistic interactions against Escherichia coli ATCC 25922. In the PCA and HCA analyses, streptomycin stood out and formed a separate group.


Assuntos
Antibacterianos/farmacologia , Apiaceae/química , Óleos Voláteis/farmacologia , Antagonismo de Drogas , Sinergismo Farmacológico , Cromatografia Gasosa-Espectrometria de Massas , Testes de Sensibilidade Microbiana , Óleos Voláteis/análise
19.
IEEE Int Conf Rehabil Robot ; 2011: 5975369, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22275573

RESUMO

We investigated dynamic optimization as a tool to improve functional electrical stimulation (FES) assisted sit to stand transfers of paraplegic subjects. The objective would be to find optimal strategy for voluntary trunk movement, which would minimize hip, knee and ankle torques and demand minimal upper limb participation during the motion. Motion of the knee and the ankle were constrained by electrical stimulation. Motion capture (MOCAP) data, and signals from handle force sensors were acquired during FES-assisted rising motion of one paraplegic subject. Based on a 3 DOF dynamic model, we used an optimization algorithm in order to determine optimal trajectories in terms of minimizing joint torques for various conditions of force level applied to handles. Motion computed using the optimization process is compared with the one recorded during the experiment. Our results suggest that in order to minimize the sum of joint torques and arm effort participation, paraplegic patients should bend their body forward in order to use linear momentum of the trunk in sit off phase. This information can be used to design controller for closed-loop FES-assisted standing-up. The controller could use trunk motion to trigger legs stimulation in order to optimize body segment coordination.


Assuntos
Estimulação Elétrica/instrumentação , Estimulação Elétrica/métodos , Extremidade Inferior/fisiologia , Paraplegia/reabilitação , Algoritmos , Humanos , Movimento/fisiologia , Postura
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