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Lead (Pb) induces oxidative stress in plants, which results in different responses, including the production of antioxidants and changes in the profile of secondary metabolites. In this study, the responses of Scrophularia striata exposed to 250mgL-1 Pb (NO3 )2 in a hydroponic environment were determined. Growth parameters, oxidative and antioxidative responses, redox status, and the concentration of Pb were analysed in roots and shoots. Malondialdehyde and hydrogen peroxide (H2 O2 ) levels in the roots were significantly increased and reached their highest value at 72h after Pb treatment. Superoxide dismutase, catalase, and peroxidase, as an enzymatic antioxidant system, were responsible for reactive oxygen species scavenging, where their activities were increased in the shoot and root of Pb-treated plants. Enzymatic antioxidant activities were probably not enough to remove a significant H2 O2 content in response to Pb treatment. Therefore, other defence responses were activated. The results stated that the flavonoid components of S. striata progressed towards the increase of isoflavone, flavanol, and stilbenoid contents under Pb treatment. In general, S. striata stimulates the enzymatic defence system and activates the non-enzymatic system by modulating the profile of flavonoids toward the production of flavonoids with high antioxidant activity, such as quercetin and myricetin in response to Pb stress.
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Antioxidantes , Flavonoides , Peróxido de Hidrogênio , Chumbo , Estresse Oxidativo , Raízes de Plantas , Scrophularia , Antioxidantes/metabolismo , Chumbo/metabolismo , Chumbo/toxicidade , Flavonoides/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Raízes de Plantas/metabolismo , Raízes de Plantas/efeitos dos fármacos , Peróxido de Hidrogênio/metabolismo , Scrophularia/metabolismo , Malondialdeído/metabolismo , Superóxido Dismutase/metabolismo , Catalase/metabolismo , Brotos de Planta/efeitos dos fármacos , Brotos de Planta/metabolismoRESUMO
BACKGROUND: External iliac artery endofibrosis (EIAE) is a rare vascular disease which has been traditionally seen in avid cyclists. The conventional approach has been surgery, although no high-quality evidence suggests superiority of surgery over percutaneous endovascular intervention. There are limited data on the efficacy of stenting in EIAE. METHODS: Over a 14-year period, we treated 10 patients (13 limbs) with EIAE with stents. These patients had declined surgery. The mean follow up was 8.4 ± 3.3 years. There were eight women. Five patients were competitive runners, three were cyclists, and two were triathletes. The mean age was 40.7 ± 2.9 years and body mass index was 19.46 ± 1.6. Intravascular ultrasound (IVUS) was used in eight limbs. RESULTS: Procedural success was achieved in all. The recurrence of symptoms occurred in three patients at a mean of 9.3 ± 2.1 months postindex intervention. The other seven patients remained symptom free. IVUS revealed a pathognomonic finding which we termed 'perfect circle appearance'. It results from symmetric or asymmetric hypertrophy of one or more layers of the arterial wall leading to negative remodeling, which creates a distinct echo dense structure contrasting itself from the luminal blood's echoluscent appearance. It is identical to IVUS images of diffuse venous stenosis with important implications in the treatment technique. CONCLUSIONS: We conclude that stenting in EIAE is safe and effective with a good long-term outcome. It can be an alternative to surgery, particularly in those patients who refuse a surgical approach. The IVUS image is pathognomonic and 'sine qua non' of EIAE.
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Fibrose , Artéria Ilíaca , Stents , Ultrassonografia de Intervenção , Humanos , Feminino , Masculino , Artéria Ilíaca/diagnóstico por imagem , Artéria Ilíaca/cirurgia , Adulto , Fatores de Tempo , Resultado do Tratamento , Pessoa de Meia-Idade , Estudos Retrospectivos , Recidiva , Grau de Desobstrução Vascular , Procedimentos Endovasculares/instrumentação , Procedimentos Endovasculares/efeitos adversos , Doença Arterial Periférica/terapia , Doença Arterial Periférica/diagnóstico por imagemRESUMO
Background: Herbal medicines are the preferred anticancer agents due to their lower cytotoxic effects on healthy cells. Plant lignans play an important role in treating various diseases, especially cancer. The present study aimed to evaluate the effect of podophyllotoxin, pinoresinol, and lariciresinol on cellular toxicity and inducing apoptosis in fibroblasts, HEK-293, and SkBr3 cell lines. Methods: An in vitro study was conducted from 2017 to 2019 at the Faculty of Biological Sciences, Tarbiat Modares University (Tehran, Iran). The cell lines were treated for 24 and 48 hours with different concentrations of lignans. Cell viability and apoptosis were examined using MTT and flow cytometry, respectively. Expression levels of cell cycle and apoptosis regulator genes were determined using quantitative real-time polymerase chain reaction. Data were analyzed using a two-way analysis of variance followed by Tukey's HSD test. P<0.05 was considered statistically significant. Results: Podophyllotoxin significantly increased apoptosis in fibroblast cells compared to pinoresinol and lariciresinol (P<0.001). The percentage of cell viability of fibroblast cells treated for 48 hours with pinoresinol, lariciresinol, and podophyllotoxin was reduced by 49%, 47%, and 36%, respectively. Treatment with pinoresinol and lariciresinol significantly overexpressed pro-apoptotic genes and underexpressed anti-apoptotic genes in SkBr3 cells (P<0.001). SkBr3 cells treated with lariciresinol significantly reduced gene expression (P<0.001). Conclusion: Pinoresinol and lariciresinol can potentially be used as new therapeutic agents for the treatment of breast cancer.
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Antineoplásicos , Neoplasias da Mama , Furanos , Lignanas , Humanos , Feminino , Podofilotoxina/análise , Oxirredutases/genética , Oxirredutases/metabolismo , Células HEK293 , Irã (Geográfico) , Lignanas/análise , Lignanas/metabolismoRESUMO
Aminoacyl-tRNA synthetases are crucial enzymes involved in protein synthesis and various cellular physiological reactions. Aside from their standard role in linking amino acids to the corresponding tRNAs, they also impact protein homeostasis by controlling the level of soluble amino acids within the cell. For instance, leucyl-tRNA synthetase (LARS1) acts as a leucine sensor for the mammalian target of rapamycin complex 1 (mTORC1), and may also function as a probable GTPase-activating protein (GAP) for the RagD subunit of the heteromeric activator of mTORC1. In turn, mTORC1 regulates cellular processes, such as protein synthesis, autophagy, and cell growth, and is implicated in various human diseases including cancer, obesity, diabetes, and neurodegeneration. Hence, inhibitors of mTORC1 or a deregulated mTORC1 pathway may offer potential cancer therapies. In this study, we investigated the structural requirements for preventing the sensing and signal transmission from LARS to mTORC1. Building upon recent studies on mTORC1 regulation activation by leucine, we lay the foundation for the development of chemotherapeutic agents against mTORC1 that can overcome resistance to rapamycin. Using a combination of in-silico approaches to develop and validate an alternative interaction model, discussing its benefits and advancements. Finally, we identified a set of compounds ready for testing to prevent LARS1/RagD protein-protein interactions. We establish a basis for creating chemotherapeutic drugs targeting mTORC1, which can conquer resistance to rapamycin. We utilize in-silico methods to generate and confirm an alternative interaction model, outlining its advantages and improvements, and pinpoint a group of novel substances that can prevent LARS1/RagD interactions.Communicated by Ramaswamy H. Sarma.
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Neoplasias , Transdução de Sinais , Humanos , Leucina/química , Leucina/metabolismo , Leucina/farmacologia , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Aminoácidos/metabolismo , Sirolimo , Neoplasias/metabolismoRESUMO
High concentration of aluminum (Al) in drinking water is a major intake source of it and can result in serious diseases. Rice straw (RS) as lignocellulosic biomasses has great potential to peak up metal ions from aqueous environment, however, feasibility of Al3+ removal by RS has not been investigated yet. The present study aimed to evaluate the capacity of RS as a novel biosorbent for Al3+ from drinking water. Biosorption characteristics of RS were surveyed through several biological and physiochemical techniques. Additionally, isotherm, kinetic and thermodynamic studies were evaluated using various common models. BET profiles revealed the presence of textural mesoporosity on heterogeneous surface, which leading to improve the biosorption capacity. SEM-EDS analysis confirmed the morphological changes as irregularly particles of Al3+ on external surface via physical mechanism. The results of bioassays and FTIR analysis showed carboxylic and hydroxyl groups in lignin and pectin as the main Al3+ binding site. The batch experimental results showed the maximum biosorption capacity of 283.09 mg/g and removal efficiency of 94.86% for Al3+ at biosorbent dosage of 0.05 g/100 mL, contact time of 50 min, pH 7.5, and temperature of 30 °C. The Freundlich model has the best match and suggests the biosorption process as a multi-layer. According to the results of free activation energy, biosorption process was also physical. As thermodynamic result, the biosorption behavior was found spontaneous and endothermic. Consequently, results showed RS as an economical biosorbent for reducing Al3+ of drinking water. Meanwhile, it can be considered as one of the most appropriate methods for management of rice paddies waste.
This article provides a new interdisciplinary horizon at the border of plant biochemistry, agriculture, water treatment industry, and environmental protection. This study covers different aspects including biosorption, cell wall network as well as the usefulness of agricultural by-products in biosorption of Al-polluted drinking water. Findings of the present study revealed that rice straw cell wall polysaccharides have specific Al3+ binding sites, therefore can be effectively used in water treatment and reduce Al3+ content below the standard permissible limit of WHO (0.2 mg/L). This can be a foundation for future research to evaluate agricultural wastes management in the industry of water as natural biosorbent. This method also effectively converts RS from an unwanted agricultural waste to high-value products.
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Plant systems have been considered valuable models for addressing fundamental questions of microtubule (MT) organization due to their considerable practical utility. Protein acetylation is a very common protein modification, and therate of acetylation can be modulated in cells in different biological states, and these changes can be detected at a molecular level. Here, we focused on K40, K112, and K394 residues as putative acetylation sites, which were shown to exist in both plants and mammals. Such residual effect of acetylation causes critical but unclear effect on MT stability. In turn, it was shown that acetylation indirectly affects the probability of interaction with different MAPs (Microtubule-associated proteins). In a multiscale study using an all-atom force field to reproduce several lattice-forming elements found on the surface the microtubule, we assembled a fragment of a plant microtubule composed of nine tubulins and used it as a model object along with the existing human complex. Triplets of tubulins assembled in a lattice cell were then simulated for both human and plant protein complexes, using a coarse-grained force field. We then analyzed the trajectories and identified some critical deformations of the MAP interaction surface. The initial coordinates were used to investigate the structural scenario in which autophagy-related protein 8 (ATG8) was able to interact with the MT fragment.
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Lisina , Microtúbulos , Animais , Humanos , Lisina/metabolismo , Acetilação , Microtúbulos/metabolismo , Tubulina (Proteína)/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Mamíferos/metabolismoRESUMO
Linum album accumulates lignans e.g., podophyllotoxin (PTOX) and 6-methoxy podophyllotoxin (6MPTOX). This study was aimed to figure out how different concentrations of MeJA (0, 50, 100, 150, and 200 µM) by affecting on free sugars and amino acids contents induce lignans accumulation in L. album cells. Results revealed that hydrogen peroxide (H2O2) content increased at 50µM, while it decreased at the high levels of MeJA (150 and 200 µM). Also, increasing trend of nitric oxide (NO) and lipid peroxidation levels peaked at 200 µM MeJA. An increased antioxidant enzymes activity was also observed in the treated cells. Moreover, an increase in rhamnose/xylose, glucose, and mannose was detected at 150 and 200 µM MeJA compared to the control. These compounds provide energy source and carbon skeleton for amino acids biosynthesis. Our results emphasized variations in amino acids levels in the presence of MeJA, where Phe level shifts along with synthesizing phenolics. Likewise, MeJA treatment switch on phenyl-ammonia lyase (PAL) and tyrosine-ammonia lyase (TAL) activities that regenerate phenolic compounds. Changes in phenolic acids (cinnamic, coumaric, caffeic, ferulic, and salicylic acid) and flavonoids (catechin, vitexin, myricetin, and kaempferol) were observed under MeJA treatment. Eventually, MeJA induced lignans production except for lariciresinol (LARI), so that the highest amounts of PTOX and 6MPTOX were analyzed at 50 µM, which were 4 and 5 time of control, respectively. Conclusively, it can be suggested that MeJA-induced oxidative status change redirects free sugars and amino acids toward the production of phenolic compounds especially lignans in L. album cells.
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Amônia-Liases , Linho , Lignanas , Podofilotoxina/metabolismo , Aminoácidos/metabolismo , Peróxido de Hidrogênio/metabolismo , Lignanas/farmacologia , Acetatos/farmacologia , Acetatos/metabolismo , Ciclopentanos/farmacologia , Ciclopentanos/metabolismo , Oxilipinas/farmacologia , Oxilipinas/metabolismo , Carboidratos , Açúcares/metabolismo , Amônia-Liases/metabolismoRESUMO
Melatonin is a pleiotropic molecule that can influence various aspects of plant performance. Recent studies have exhibited that it mediates plant defensive responses, probably through managing redox homeostasis. We tried to track the regulatory effects of melatonin on the antioxidant machinery of Linum album cell culture. To this, different concentrations of melatonin were applied, and the oxidative status of cells was investigated by measuring the levels of oxidative molecules and antioxidant agents. The results showed that H2O2 content did not change at the low melatonin levels, while it increased at the high concentrations. It can be correlated with the low melatonin dosages capacity to remove excessive amounts of H2O2, while the high melatonin dosages exhibit toxicity effects. In contrast, the NO enhancement occurred at 50 µM melatonin, proposing its role in triggering melatonin-induced defensive responses. The MDA results stated that NO led to oxidative stress in melatonin-treated cells at 50 µM melatonin. Antioxidant enzyme POD was activated by melatonin treatment, while SOD enzyme behaved reversely which can explain the changes in the H2O2 level. In addition, the analysis of the phenolics profile showed that the contents of phenolic acids, flavonoids, and lignans enhanced following an increase in PAL enzyme activity. The increased level of phenolic hormone SA can indicate that melatonin affects the defensive responses in L. album cells through a SA-dependent pathway. In general, it seems that melatonin, by modulating NO and SA levels, can induce the activity of antioxidant enzymes and the production of phenolics, especially lignans, in L. album cells.
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Linho , Lignanas , Melatonina , Melatonina/farmacologia , Melatonina/metabolismo , Antioxidantes/metabolismo , Óxido Nítrico/metabolismo , Linho/metabolismo , Ácido Salicílico/farmacologia , Ácido Salicílico/metabolismo , Peróxido de Hidrogênio/metabolismo , Fenóis/farmacologia , Fenóis/metabolismo , Lignanas/metabolismoRESUMO
Context: Patients with inflammatory bowel disease (IBD) were found to have the higher intestinal expression of Angiotensin-Converting Enzyme2 (ACE2) that could consequently increase susceptibility to COVID-19 infection.Objective: This study reports the outcomes of COVID-19 infection in a large cohort of IBD patients. We compare levels of serum ACE and IFN-α between COVID19 patients with and without IBD. We performed a cross-sectional retrospective multicenter study.Methods: We enrolled patients with IBD screened for SARS-COV-2 in six medical centres in Iran from June to November 2020. The blood samples were drawn to measure COVID-19 IgM and IgG, and serum levels of sACE2, sACE1, and interferon-α, regardless of suspicious symptoms have done the molecular test.Results: A total of 534 IBD patients were included in the study. Of these, 109 (20.0%) cases had detectable IgG and IgM against SARS-CoV-2. sACE2 levels were higher in IBD patients than controls, whereas ACE1and IFN-α levels were similar among groups.
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Increasing pollutants such as hydrogen sulfide (H2S) from industrial activities is an ecological challenge for plants, which seriously affects their health and productivity. Scrophularia striata is a plant endemic to Iran growing in the province of Ilam, wherein a gas refinery releases toxic agents such as H2S whose detrimental effects on the function and tolerability of medicinal plants in this region have yet to be elucidated. Thus, we initiated a hydroponic study into hormetic effect of sodium hydrogen sulfide (NaHS) concentrations (0, 3 and 7 mM) as H2S-donor at different time points on oxidative status and phenolic compounds, focusing more on phenylethanoid glycosides (PhGs) in S. striata. Our results indicated that hydrogen peroxide (H2O2) increased significantly at 3 mM NaHS after 48 h, while its peak at 7 mM occurred after 24 h. Nitric oxide (NO) level peaked at 3 mM and 7 mM after 24 h. Treatment with NaHS also resulted in a dose-dependent induction of phenylalanine ammonia-lyase (PAL) and tyrosine ammonia-lyase (TAL) enzyme activities, phenolic acids production (cinnamic acid, coumaric acid, ferulic acid, caffeic acid and salicylic acid) and acteoside accumulation, ultimately leading to an increase in antioxidant capacity. Modulation of soluble sugars contents including glucose, mannose and rhamnose/xylose, occurred after the treatment with NaHS, likely increasing plant tolerance due to their biological activity and structural effects. Overall, our results suggest that dose-dependent accumulation of phenolics, notably acteoside, leads to an augmentation in antioxidant system to deal with H2S stress in S. striata.
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Sulfeto de Hidrogênio , Scrophularia , Antioxidantes/farmacologia , Peróxido de Hidrogênio/farmacologia , Sulfeto de Hidrogênio/farmacologia , Fenilalanina Amônia-LiaseRESUMO
The plant cell wall is a flexible physical barrier surrounding the cell which functions in growth and differentiation, signaling, and response to environmental stimuli including the Earth gravity force. In the present study, structural and molecular modifications of cell wall components of cultured tobacco (Nicotiana tabacum cv. Burley 21) cells under alternative gravity conditions induced by 7 days exposure to 2-D clinostat have been investigated. In comparison with the control group, clinorotation significantly increased biomass but reduced the total amounts of wall and the contents of cellulose, pectin, uronic acidic, and xyloglucan. Gene expression of H+-ATPase was not changed but of expansin A reduced in clinostat-treated cells. However, the gene expression and activity of xyloglucan endotransglycosylase/hydrolases (XTH; EC 2.4.1.207) and endo-(1,4)-ß-D-glucanase (EGase; EC 3.2.1.4), the amount of arabinogalactan proteins (AGP), and the expression of wall-associated kinase (WAK) gene significantly increased by clinorotation. Altered gravity also reduced the activity of polyphenol oxidase and covalently bound peroxidase. The results suggest that altered gravity promoted orchestrated changes of wall-modifying genes and proteins which reduced its stiffness and enhanced cell expansion and division potential.
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Glicosiltransferases , Nicotiana , Parede Celular/metabolismo , Células Cultivadas , Celulose/metabolismo , Glicosiltransferases/metabolismo , Pectinas/metabolismo , Nicotiana/genética , Nicotiana/metabolismoRESUMO
Soils and oak trees (Quercus brantii Lindl.) in Zagros forests are suffering from the air pollution caused by the Ilam Gas Refinery. Thus, for the first time, we investigated the contamination level of sulfur and trace elements in these ecosystems. Sampling of soil and tree leaves was carried out in different seasons of 2019 and at different distances from the gas refinery. The results showed that soils and leaves at the various distances compared with control distance (10,000 m) were more affected by the gas refinery. Distance from the pollution source and physicochemical properties of soils were the main factors affecting contamination of soil elements contents. The soils with pollution load indices (PLI) of 4.54 were in the highly polluted category. Sulfur was at highly polluted category in soils and were highly enriched in trees. The trees mainly absorbed studied elements via their aerial organs. Our findings indicated that oak trees with the highest value of metal accumulation index are influence tools for monitoring various elements in the polluted air produced by the gas refinery. It is recommended that the ecosystem components near the refinery be studied to accurately evaluate disorders in the food chain.
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Poluentes Atmosféricos/análise , Poluição do Ar , Florestas , Metais/análise , Indústria de Petróleo e Gás , Quercus/química , Solo/química , Enxofre/análise , Árvores/química , Poluentes Atmosféricos/toxicidade , Ecossistema , Exposição Ambiental , Monitoramento Ambiental , Irã (Geográfico) , Metais/toxicidade , Folhas de Planta/química , Folhas de Planta/efeitos dos fármacos , Quercus/efeitos dos fármacos , Medição de Risco , Estações do Ano , Enxofre/toxicidade , Árvores/efeitos dos fármacosRESUMO
Air pollution around refineries and factories is one of the major environmental challenges affecting forest ecosystems' health. Although there have been many studies on Iran's forest ecosystems, the physiological and morphological responses of Brant's oak (Quercus brantii Lindl.) leaves to the pollution of the gas refineries in the semiarid forests have not received much attention. We sampled healthy and mature leaves from four oak stands in different seasons (spring, summer, and autumn of 2019) and at various distances from the gas refinery (1,000, 1,500, 2,000, 2,500, and 10,000 m). The results showed that oak trees in different seasons and at different distances from the refinery had different physiological and morphological leaf trait responses to the pollution source. Oak trees with an air pollution tolerance index value of less than 11 were in a sensitive range to air pollution and can be used to biomonitor air pollution around the gas refinery in Zagros forests. Physiological traits in different seasons and at various distances in comparison with morphological traits (persistent reaction responses) were well distinguished from one another and were more affected by pollution. Oak trees in summer and autumn and at distances up to 2,500 m had rapid reaction responses, including oxidative stress indicators such as electrolyte leakage (EL), hydrogen peroxide, and different enzymatic and nonenzymatic antioxidants such as phenol, flavonoids, catalase, and proline. Because of their high sensitivity to atmospheric pollutant stresses, we recommend that these traits be used for rapid and low-cost environmental monitoring of pollution in different seasons and distances from pollution sources in semiarid ecosystems.
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Quercus , Ecossistema , Florestas , Irã (Geográfico) , Folhas de Planta , Estações do Ano , ÁrvoresRESUMO
Phenylethanoid glycosides (PhGs) are important medicinal compounds found in Scrophularia striata, one of the plant species native to Iran. Since almost all aspects of plant life are controlled by night/light cycle, studying its relationship to valuable plant metabolites production will help us to determine the right time for their extraction. Therefore, the aim of this investigation is to figure out whether the diel light oscillations control PhGs production and how it relates to daily changes in upstream metabolic reactions and circadian clock in S. striata. For this, daily rhythms of metabolic pathways were examined every 4 h during a day/night cycle in 3 groups of control (16 h light/8 h dark), continuous light and darkness. The results showed that acteoside and echinacoside levels in each group peaked during the night and day, respectively. Thus, the PhGs production follows a rhythmic behavior in S. striata, which is probably controlled by circadian clock. Also, the levels of photosynthetic pigments, carbohydrates, amino acids, phenolic acids, phytohormones and phenylalanine ammonia-lyase (PAL) and tyrosine ammonia-lyase (TAL) enzyme activities varied diel in a similar or different way among study groups. The observations revealed that light/dark cycle controls the carbon and energy flow from light reception to the production and consumption of starch, biosynthesis of phenylalanine, tyrosine, cinnamic acid and coumaric acid, activation of hormonal signaling pathways and enzymes involved in phenylpropanoid pathway. Overall, it can be concluded that PhGs accumulation time-dependent patterns is likely due to daily fluctuations in upstream metabolic reactions induced by light/dark cycle.
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Glicosídeos/biossíntese , Fotoperíodo , Scrophularia/metabolismo , Redes e Vias Metabólicas , Fenilalanina Amônia-Liase/metabolismo , Fotossíntese , Reguladores de Crescimento de Plantas/metabolismo , Scrophularia/fisiologiaRESUMO
Background: In the absence of SARS-CoV-2 specific antiviral treatments, various repurposed pharmaceutical approaches are under investigation for the treatment of COVID-19. Antiviral drugs considered for this condition include atazanavir, remdesivir, lopinavir-ritonavir, and favipiravir. Whilst the combination of lopinavir and ritonavir has been previously linked to prolongation of the QTc interval on the ECG and risk of torsades de pointes arrhythmia, less is known in this regard about atazanavir, remdesivir, and favipiravir. Unwanted abnormalities of drug-induced QTc prolongation by diverse drugs are commonly mediated by a single cardiac anti-target, the hERG potassium channel. This computational modeling study was undertaken in order to explore the ability of these five drugs to interact with known determinants of drug binding to the hERG channel pore. Methods: Atazanavir, remdesivir, ritonavir, lopinavir and favipiravir were docked to in silico models of the pore domain of hERG, derived from cryo-EM structures of hERG and the closely related EAG channel. Results: Atazanavir was readily accommodated in the open hERG channel pore in proximity to the S6 Y652 and F656 residues, consistent with published experimental data implicating these aromatic residues in atazanavir binding to the channel. Lopinavir, ritonavir, and remdesivir were also accommodated in the open channel, making contacts in a model-dependent fashion with S6 aromatic residues and with residues at the base of the selectivity filter/pore helix. The ability of remdesivir (at 30 µM) to inhibit the channel was confirmed using patch-clamp recording. None of these four drugs could be accommodated in the closed channel structure. Favipiravir, a much smaller molecule, was able to fit within the closed channel and could adopt multiple binding poses in the open channel, but with few simultaneous interactions with key binding residues. Only favipiravir and remdesivir showed the potential to interact with lateral pockets below the selectivity filter of the channel. Conclusions: All the antiviral drugs studied here can, in principle, interact with components of the hERG potassium channel canonical binding site, but are likely to differ in their ability to access lateral binding pockets. Favipiravir's small size and relatively paucity of simultaneous interactions may confer reduced hERG liability compared to the other drugs. Experimental structure-function studies are now warranted to validate these observations.
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Sexual function is essential for species survival. Melanocortin, progesterone, and estrogen can improve sexual function and they are modulated by adiponectin hormone which can be increased by Turmeric. In various studies shows Turmeric ability that is easily accessible to increase serum adiponectin levels. Therefore, the researchers decided to conduct a study to determine the effect of turmeric on serum adiponectin levels, sexual behavior, and profile of steroid hormones in stressed mice. Thirty female mice, six in each group (1. control group, 2. mice that received stress, 3. stress mice received 100 mg/kg turmeric (extract daily) for 4 weeks, 4. stress mice received turmeric (extract daily) for 4 weeks and also received adiponectin antagonist, and 5. stress groups received adiponectin antagonist), were used in the current study. The mice first underwent blood sampling. Then all mice were subjected to stress testing before the intervention except one group, which considered as a control group. The intervention in this study was done as a 100 mg/kg turmeric extract that was gavaged daily for each mouse. After the intervention, all mice were tested for sexual behavior, and then blood samples were taken to check serum levels of adiponectin, estradiol, progesterone and prolactin. So, the results showed before the intervention there were no significant difference among 5 group in levels of adiponectin (p = 0.145), estradiol (p = 0.148), progesterone (p = 0.166) and prolactin (p = 0.206) but after intervention there were significant difference between 5 group in levels of adiponectin, estradiol and progesterone (p < 0.001). Also there was significant difference among 5 groups in sexual behavior (p < 0.001). Therefore, consumption of turmeric, which increases serum adiponectin in the stressed mice, can improve sexual function and estradiol hormones profiling.
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Curcuma/metabolismo , Hormônios Esteroides Gonadais/metabolismo , Extratos Vegetais/farmacologia , Adiponectina/metabolismo , Animais , Estradiol/análise , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/análise , Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/análise , Hormônio Luteinizante/sangue , Camundongos , Camundongos Endogâmicos C57BL , Progesterona/análise , Progesterona/sangue , Prolactina/análise , Prolactina/sangue , Comportamento Sexual/fisiologia , Estresse Fisiológico/efeitos dos fármacosRESUMO
An important aspect of molecular mechanics simulations of a protein structure and ligand binding often involves the generation of reliable force fields for nonstandard residues and ligands. We consider the aminoacyl-tRNA synthetase (AaRS) system that involves nucleic acid and amino acid derivatives, obtaining force field atomic charges using the restrained electrostatic potential (RESP) approach. These charges are shown to predict observed properties of the post-transfer editing reaction in this system, in contrast to simulations performed using approximate charges conceived based upon standard charges for related systems present in force field databases. In particular, the simulations predicted key properties induced by mutation. The approach taken for generating the RESP charges retains established charges for known fragments, defining new charges only for the novel chemical features present in the modified residues. This approach is of general relevance for the design of force fields for pharmacological applications, and indeed the AaRS target system is itself relevant to antibiotics development.
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Plants synthesize a variety of metabolites in response to biotic elicitors. To comprehend how the digested cell wall of Piriformospora indica affects the response of ROS burst, antioxidant enzymes, amino acids profiling, and phenylpropanoid compounds such as lignans, phenolic acids, and flavonoids in Linum album hairy roots; we accomplished a time-course analysis of metabolite production and enzyme activities in response to CDCW and evaluated the metabolic profiles. The results confirms that CDCW accelerates the H2O2 burst and increases SOD and GPX activity in hairy roots. The HPLC analysis of metabolic profiles shows that the H2O2 burst shifts the amino acids, especially Phe and Tyr, fluxes toward a pool of lignans, phenolic acids, and flavonoids through alterations in the behavior of the necessary enzymes of the phenylpropanoid pathway. CDCW changes PAL, CCR, CAD, and PLR gene expression and transiently induces PTOX and 6MPROX as the main-specific products of PAL and PLR genes expression. The production of phenolic acids (e.g., cinnamic, coumaric, caffeic, and salicylic acid) and flavonoids (e.g., catechin, diosmin, kaempferol, luteolin, naringenin, daidzein, and myricetin) show different behaviors in response to CDCW. In conclusion, our observations show that CDCW elicitation can generate H2O2 molecules in L. album hairy roots and consequently changes physiological, biochemical, and molecular responses such as antioxidant system and the specific active compounds such as lignans. Quantification of metabolic contents in response to CDCW suggests enzyme and non-enzyme defense mechanisms play a crucial role in L. album hairy root adaptation to CDCW. A summary revealed that the correlation between H2O2 generation and L. album hairy root defense system under CDCW. Increase of H2O2 generation led plant to response against oxidative conditions. SOD, and GPX modulated H2O2 content, Phe, and Tyr shifted to the phenylpropanoid compounds as a precursor of PAL and TAL enzyme, the predominant phenylpropanoid compounds controlled oxidative conditions, and the other amino acids responsible for amino acid synthesis and development stages.
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OBJECTIVE: There are conflicting reports on the efficacy of exercise in chronic venous insufficiency (CVI). Exercise in water or aquatic activity (AA) can have additional advantages. We sought to evaluate the clinical effects of AA in CVI in a randomized prospective open label fashion. METHODS: A total of 201 patients with advanced CVI were randomized to receive AA vs no such treatment. In the Aquatic Group (AG), 91 patients reached the 24-month follow-up point, and in the Control Group (CG), 90 patients did. The primary efficacy end point was a predefined reduction of ≥4 points in the modified Venous Clinical Severity Score (VCSS) at 3 months. Instruments of venous disease severity and quality of life were compared at baseline, 3 months, and 24 months between and within the two groups. These included the modified VCSS, Villalta score, leg and thigh circumference, the Physical Health Component of the 36-Item Short Form Health Survey, and the Venous Insufficiency Epidemiological and Economic Study Quality of Life/Symptom scores. Aquatic activity consisted of a minimum of 15 minutes of walking in a swimming pool at 1 m/s, 3 times/wk for 3 months. RESULTS: The primary end point of 4-point reduction in the modified VCSS at 3 months was reached in 28% of AG and 3% of CG (odds ratio = 12.08; 95% confidence interval: 3.51, 41.59; P < .001). Comparison of changes in secondary end points from baseline to 24 months between AG and CG demonstrated the following: modified VCSS -4.08 ± 2.08 vs -1.15 ± 1.26, Villalta score -4.00 ± 2.68 vs -1.01 ± 1.34, thigh circumference -3.40 ± 1.78 cm vs -1.40 ± 2.55 cm, leg circumference -1.27 ± 1.34 cm vs -0.49 ± 1.21 cm, Physical Health Component of the 36-Item Short Form Health Survey 3.82 ± 2.36 vs 1.16 ± 1.18, Venous Insufficiency Epidemiological and Economic Study Quality of Life 3.35 ± 1.67 vs 1.30 ± 1.43, and Venous Insufficiency Epidemiological and Economic Study Symptom 3.53 ± 1.71 vs 1.23 ± 1.26 (P < .001 for all comparisons; ± denotes mean ± standard deviation). CONCLUSIONS: The addition of AA to the treatment of patients with advanced CVI is safe and effective, leading to a significant improvement in clinical status and quality of life. These beneficial changes occur rapidly within 3 months of initiation of AA and are continued at a slower rate of improvement from 3 months to 2 years.
Assuntos
Fisioterapia Aquática , Insuficiência Venosa/terapia , Adulto , Idoso , Doença Crônica , Edema/etiologia , Edema/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Índice de Gravidade de Doença , Resultado do Tratamento , Insuficiência Venosa/complicaçõesRESUMO
KEY MESSAGE: MeJA triggers a time-dependent behavior of the phenylpropanoid compounds. Plant cells produce a large number of metabolites in response to environmental factors. The cellular responses to environmental changes are orchestrated by signaling molecules, such as methyl jasmonate (MeJA). To understand how the MeJA changes the behavior of amino acids, carbohydrates, and phenylpropanoid compounds such as phenolic acids, phenylethanoid-glycosides, and flavonoids in Scrophularia striata cells; we monitored the metabolic responses for different times of exposure. In this study, we performed a time course analysis of metabolites and enzymes in S. striata cells exposed to MeJA (100 µM) and evaluated the metabolic flux towards carbon-rich secondary metabolites production. Moreover, we calculated the biosynthetic energy cost for free amino acids. Our results indicated that MeJA accelerates the sucrose degradation and directs the metabolic fluxes towards a pool of flavonoids and phenylethanoid glycosides through a change in enzyme behavior in the entry point and center of the phenylpropanoid pathway. MeJA also decreased and then raised the amino acid biosynthesis cost in S. striata cells in a time-dependent manner, indicating the cells evolve to utilize amino acids more economically by reducing cell growth. Finally, we classified the marked changes in the metabolites level and enzyme activities into three groups including early-, late-, and oscillatory-response groups to MeJA and summarized our findings as a model depicting pathway interactions during MeJA elicitation. Determination of metabolic levels in response to MeJA suggests that the changes in metabolic responses are time-dependent.