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1.
Curr Issues Mol Biol ; 46(8): 8726-8740, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-39194732

RESUMO

This study aimed to evaluate the efficacy of the ethanolic extract of Anadenanthera colubrina in modulating the immune response in the Experimental Autoimmune Encephalomyelitis (EAE) model. The ethanolic extract of the dried bark was analyzed by ESI (+) Orbitrap-MS to obtain a metabolite profile, demonstrating a wide variety of polyphenols, such as flavonoids and phenolic acids. Various parameters were evaluated, such as clinical signs, cytokines, cellular profile, and histopathology in the central nervous system (CNS). The ethanolic extract of A. colubrina demonstrated significant positive effects attenuating the clinical signs and pathological processes associated with EAE. The beneficial effects of the extract treatment were evidenced by reduced levels of pro-inflammatory cytokines, such as IL1ß, IL-6, IL-12, TNF, IFN-γ, and a notable decrease in several cell profiles, including CD8+, CD4+, CD4+IFN-γ, CD4+IL-17+, CD11c+MHC-II+, CD11+CD80+, and CD11+CD86+ in the CNS. In addition, histological analysis revealed fewer inflammatory infiltrates and demyelination sites in the spinal cord of mice treated with the extract compared to the control model group. These results showed, for the first time, that the ethanolic extract of A. colubrina exerts a modulatory effect on inflammatory processes, improving clinical signs in EAE, in the acute phase of the disease, which could be further explored as a possible therapeutic alternative.

2.
Toxins (Basel) ; 16(7)2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-39057924

RESUMO

Botulism is one of the most serious food intoxications, manifesting as prolonged paralytic conditions. This disease is usually the result of the consumption of poor quality canned or smoked foods, so the inhabitants of many countries of the world are exposed to the risk of this kind of poisoning every year. In view of the severity of poisonings caused by botulinum neurotoxins, monoclonal antibodies (mAbs) show great promise because of their targeting action, lack of allergic reactions and serum sickness. The use of a cocktail of mAbs increases the "functional specificity" of their mixture, allowing them to bind to the active domains of different toxin chains and block their action. In this work, we obtained 14 murine mAbs to the catalytic and receptor-binding domain of botulinum toxin type A. The Sp2/0-Ag14 murine myeloma cell line and splenocytes from immunized mice of the BALB/c line were used as fusion partners. We have shown that the selected cocktail of three antibodies neutralizes native toxin more effectively than antibodies separately-complete neutralization is achieved at a toxin dose of 3LD50 and partial neutralization at 5LD50. We presume that this cocktail may be promising as a prototype for the creation of a therapeutic drug capable of neutralizing the toxin in the blood of patients.


Assuntos
Anticorpos Monoclonais , Toxinas Botulínicas Tipo A , Camundongos Endogâmicos BALB C , Animais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/imunologia , Toxinas Botulínicas Tipo A/imunologia , Toxinas Botulínicas Tipo A/toxicidade , Botulismo/tratamento farmacológico , Botulismo/imunologia , Camundongos , Linhagem Celular Tumoral , Feminino , Anticorpos Neutralizantes/imunologia
3.
Plants (Basel) ; 13(7)2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38611448

RESUMO

We performed next-generation sequencing of the 18S rDNA-ITS1-5.8S rDNA region along with traditional Sanger sequencing of rbcL, matK, ndhF, and ITS1-5.8S rDNA-ITS2 to clarify the hybridization pattern in the subtribe Alopecurinae and in the genus Alopecurus in particular. Our data support the hybrid origin of Alopecurus × brachystylus from hybridization between A. geniculatus (sect. Alopecurium) and A. pratensis (sect. Alopecurus). Moreover, in the rDNA of hybrid A. × brachystylus, only A. aequalis-like ribotypes from tetraploid A. geniculatus participated. Surprisingly, we found the traces of introgression of A. arundinaceus-like ribotypes not only in hybrid A. × marssonii (A. geniculatus × A. arundinaceus) but in A. aequalis s. str. as well. A high-polyploid group from the section Alopecurus, A. aggr. alpinus has undoubted hybrid origin: e. g., A. brachystachyus has rDNA from the sect. Alopecurium. Alopecurus alpinus, with its allies, is clearly distinct from other members of the sect. Alopecurus (especially by maternal line) and thus we can re-establish a previous opinion about the separate group to which A. alpinus belongs. Species from the section Colobachne (presumably Alpine grasses from Ancient Mediterranean region) probably hybridized with the A. alpinus group. Even A. myosuroides (sect. Pseudophalaris) that could be referred to the separate genus has ribotypes common with the species of the section Alopecurium (A. aequalis, A. geniculatus) in one of the accessions. Additionally, we found that the possible polyphyletic origin of the genus Limnas. Limnas stelleri is very close to Alopecurus magellanicus according to NGS data, while L. malyschevii is more or less distinct from other studied species of the genus Alopecurus.

4.
Vaccines (Basel) ; 11(11)2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-38006064

RESUMO

Mucosal vaccination appears to be suitable to protect against SARS-CoV-2 infection. In this study, we tested an intranasal mucosal vaccine candidate for COVID-19 that consisted of a cationic liposome containing a trimeric SARS-CoV-2 spike protein and CpG-ODNs, a Toll-like receptor 9 agonist, as an adjuvant. In vitro and in vivo experiments indicated the absence of toxicity following the intranasal administration of this vaccine formulation. First, we found that subcutaneous or intranasal vaccination protected hACE-2 transgenic mice from infection with the wild-type (Wuhan) SARS-CoV-2 strain, as shown by weight loss and mortality indicators. However, when compared with subcutaneous administration, the intranasal route was more effective in the pulmonary clearance of the virus and induced higher neutralizing antibodies and anti-S IgA titers. In addition, the intranasal vaccination afforded protection against gamma, delta, and omicron virus variants of concern. Furthermore, the intranasal vaccine formulation was superior to intramuscular vaccination with a recombinant, replication-deficient chimpanzee adenovirus vector encoding the SARS-CoV-2 spike glycoprotein (Oxford/AstraZeneca) in terms of virus lung clearance and production of neutralizing antibodies in serum and bronchial alveolar lavage (BAL). Finally, the intranasal liposomal formulation boosted heterologous immunity induced by previous intramuscular vaccination with the Oxford/AstraZeneca vaccine, which was more robust than homologous immunity.

5.
Pril (Makedon Akad Nauk Umet Odd Med Nauki) ; 44(2): 99-106, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37453107

RESUMO

The glomerulopathies associated with the deposition of extracellular fibrils in the glomeruli are subdivided into Congo red positive (amyloidosis) and Congo red negative (non-amyloidotic glomerulopathies) based on Congo red staining. The non-amyloidotic glomerulopathies are divided into immunoglobulin-derived and non-immunoglobulin-derived glomerulopathies. The immunoglobulin-derived glomerulopathies: fibrillary glomerulopathy (FGn) and immunotactoid glomerulopathy (ITG) are rare glomerulopathies. The diagnosis of fibrillary-immunotactoid glomerulopathy depends on electron microscopy, which shows the presence of microfibrils in the glomeruli. The microfibrils in FGn are randomly arranged with diameters less than 30 nm. The microfibrils in ITG are larger than 30 nm with a visible lumen (microtubules), focally arranged in parallel bundles. Patients with fibrillary-immunotactoid glomerulopathy present with proteinuria (usually in the nephrotic range), microscopic hematuria, arterial hypertension, and chronic kidney disease that progresses to kidney failure over months to years. Currently, there are no guidelines for the treatment of fibrillary-immunotactoid glomerulopathy, although immunotactoid glomerulopathy could be associated with underlying hematologic disorders with the need for clone-directed therapy.


Assuntos
Glomerulonefrite , Nefropatias , Humanos , Vermelho Congo , Glomérulos Renais/ultraestrutura , Glomerulonefrite/terapia , Proteinúria
6.
Pril (Makedon Akad Nauk Umet Odd Med Nauki) ; 44(2): 107-112, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37453112

RESUMO

Peritoneal dialysis (PD) is one of the options for renal replacement therapy (RRT) in the end stage renal disease (ESRD) patients. Compared to hemodialysis (HD), patients on PD experience a greater sense of well-being, an improved steady state in terms of extracellular fluid volume shifts and hemodynamics and it is preferred method for patients with problematic vascular access, bleeding tendencies, heart failure and elderly patients. In order to perform PD, a tunneled catheter should be placed through the abdominal wall and into peritoneal space, with positioning of the catheter within the most dependent portion of pelvis. Currently, there are several techniques available for PD catheter placement: open surgery, laparoscopic and percutaneous. We present for the first time in our country a case of 65 year old male patient to whom percutaneous onsite insertion of peritoneal catheter was performed. The idea is to emphasize that sometimes this should be a method of choice for RRT, especially in patients where general anesthesia should be avoid. Compared to other methods, percutaneous insertion is a simple procedure with no need for general anesthesia, and the benefits of quick recovery, earlier ambulation, and less delay in catheter placement.


Assuntos
Falência Renal Crônica , Laparoscopia , Diálise Peritoneal , Masculino , Humanos , Idoso , Diálise Peritoneal/métodos , Cateterismo/efeitos adversos , Cateterismo/métodos , Diálise Renal , Cateteres de Demora , Falência Renal Crônica/terapia , Falência Renal Crônica/etiologia
7.
Future Microbiol ; 18: 1077-1093, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37424510

RESUMO

Aim: To access the metabolic changes caused by a chalcone derivative (LabMol-75) through a proteomic approach. Methods: Proteomic analysis was performed after 9 h of Paracoccidioides brasiliensis yeast (Pb18) cell incubation with the LabMol-75 at MIC. The proteomic findings were validated through in vitro and in silico assays. Results: Exposure to the compound led to the downregulation of proteins associated with glycolysis and gluconeogenesis, ß-oxidation, the citrate cycle and the electron transport chain. Conclusion: LabMol-75 caused an energetic imbalance in the fungus metabolism and deep oxidative stress. Additionally, the in silico molecular docking approach pointed to this molecule as a putative competitive inhibitor of DHPS.


Assuntos
Paracoccidioides , Paracoccidioidomicose , Paracoccidioides/metabolismo , Proteômica , Simulação de Acoplamento Molecular , Estresse Oxidativo , Oxirredução , Paracoccidioidomicose/microbiologia
8.
Indian J Nephrol ; 33(2): 140-143, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37234440

RESUMO

Immunotactoid glomerulopathy (ITG) is a rare glomerular disease with variable responsiveness to the immunosuppressive therapy and with uncertain prognosis. ITG was diagnosed in two patients with type 2 diabetes mellitus with nephrotic syndrome and chronic kidney disease. The absence of diabetic retinopathy in the first case and the recent onset of diabetes in the second case accompanied with sudden increase in the 24-hour proteinuria and rapid decline in kidney function, prompted us to perform kidney biopsy. The electron microscopy set the diagnosis of ITG in both cases. There is no consensus for the treatment of ITG. The first patient was treated with combination of steroids and mycophenolate mofetil with reduction of the 24-hour proteinuria, but with persistence of the chronic kidney disease. The second patient received high doses of steroids with continuous deterioration of kidney function with the need of hemodialysis treatment.

9.
Nanomaterials (Basel) ; 13(5)2023 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-36903693

RESUMO

Nowadays, magnetoelectric nanomaterials are on their way to finding wide applications in biomedicine for various cancer and neurological disease treatment, which is mainly restricted by their relatively high toxicity and complex synthesis. This study for the first time reports novel magnetoelectric nanocomposites of CoxFe3-xO4-BaTiO3 series with tuned magnetic phase structures, which were synthesized via a two-step chemical approach in polyol media. The magnetic CoxFe3-xO4 phases with x = 0.0, 0.5, and 1.0 were obtained by thermal decomposition in triethylene glycol media. The magnetoelectric nanocomposites were synthesized by the decomposition of barium titanate precursors in the presence of a magnetic phase under solvothermal conditions and subsequent annealing at 700 °C. X-ray diffraction revealed the presence of both spinel and perovskite phases after annealing with average crystallite sizes in the range of 9.0-14.5 nm. Transmission electron microscopy data showed two-phase composite nanostructures consisting of ferrites and barium titanate. The presence of interfacial connections between magnetic and ferroelectric phases was confirmed by high-resolution transmission electron microscopy. Magnetization data showed expected ferrimagnetic behavior and σs decrease after the nanocomposite formation. Magnetoelectric coefficient measurements after the annealing showed non-linear change with a maximum of 89 mV/cm*Oe with x = 0.5, 74 mV/cm*Oe with x = 0, and a minimum of 50 mV/cm*Oe with x = 0.0 core composition, that corresponds with the coercive force of the nanocomposites: 240 Oe, 89 Oe and 36 Oe, respectively. The obtained nanocomposites show low toxicity in the whole studied concentration range of 25-400 µg/mL on CT-26 cancer cells. The synthesized nanocomposites show low cytotoxicity and high magnetoelectric effects, therefore they can find wide applications in biomedicine.

10.
Ther Apher Dial ; 27(3): 530-539, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36458846

RESUMO

BACKGROUND: The determination of blood flow rate (BFR) is a useful tool for assessing the function of arteriovenous fistula (AVF). METHODS: Eighty patients with a newly created radio cephalic AVF were analyzed. Hemodynamics and morphological characteristics of the blood vessels were assessed by Doppler ultrasound. RESULTS: The mean age of patients was 59.9 ± 13.5 years. A successful rate of AVF maturation was 62.5% at 8 weeks. Six adjusted models of multivariate analysis showed that BFR at Day 1 was a predictor for AVF maturation both at 4 weeks (p < 0.001) and 8 weeks (p < 0.001). Receiver operating characteristic analysis showed an optimal cut-off point for BFR at Day 1 of 395 ml/min for successful maturation at 4 weeks (sensitivity 0.714, specificity 0.889) and 344 ml/min for successful maturation at 8 weeks (sensitivity 0.860, specificity 0.867). CONCLUSION: BFR at Day 1 is a powerful predictor for successful AVF maturation at 4 and 8 weeks.


Assuntos
Fístula Arteriovenosa , Derivação Arteriovenosa Cirúrgica , Humanos , Pessoa de Meia-Idade , Idoso , Diálise Renal , Valor Preditivo dos Testes , Hemodinâmica , Grau de Desobstrução Vascular , Resultado do Tratamento
11.
Int J Radiat Biol ; 99(5): 760-768, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36352506

RESUMO

PURPOSE: We studied the effects of computed tomography (CT) scan irradiation on proliferation and differentiation of human embryonic stem cells (hESCs). It was reported that hESC is extremely radiosensitive; exposure of hESC in cultures to 1 Gy of ionizing radiation (IR) results in massive apoptosis of the damaged cells and, thus, they are eliminated from the cultures. However, after recovery the surviving cells proliferate and differentiate normally. We hypothesized that IR-exposed hESC may still have growth rate disadvantage when they proliferate or differentiate in the presence of non-irradiated hESC, as has been shown for mouse hematopoietic stem cells in vivo. MATERIALS AND METHODS: To study such competitive proliferation and differentiation, we obtained cells of H9 hESC line that stably express green fluorescent protein (H9GFP). Irradiated with 50 mGy or 500 mGy H9GFP and non-irradiated H9 cells (or vice versa) were mixed and allowed to grow under pluripotency maintaining conditions or under conditions of directed differentiation into neuronal lineage for several passages. The ratio of H9GFP to H9 cells was measured after every passage or approximately every week. RESULTS: We observed competition of H9 and H9GFP cells; we found that the ratio of H9GFP to H9 cells increased with time in both proliferation and differentiation conditions regardless of irradiation, i.e. the H9GFP cells in general grew faster than H9 cells in the mixtures. However, we did not observe any consistent changes in the relative growth rate of irradiated versus non-irradiated hESC. CONCLUSIONS: We conclude that population of pluripotent hESC is very resilient; while damaged cells are eliminated from colonies, the surviving cells retain their pluripotency, ability to differentiate, and compete with non-irradiated isogenic cells. These findings are consistent with the results of our previous studies, and with the concept that early in pregnancy omnipotent cells injured by IR can be replaced by non-damaged cells with no impact on embryo development.


Assuntos
Células-Tronco Embrionárias Humanas , Humanos , Animais , Camundongos , Células-Tronco Embrionárias Humanas/metabolismo , Células-Tronco Embrionárias Humanas/efeitos da radiação , Células-Tronco Embrionárias/metabolismo , Diferenciação Celular , Proliferação de Células/efeitos da radiação , Radiação Ionizante
12.
Trends Psychiatry Psychother. (Online) ; 45: e20210214, 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1432489

RESUMO

Abstract Introduction The Cognitive Distortions Questionnaire (CD-Quest) is an instrument that identifies logical errors or cognitive distortions and is used in trial-based cognitive therapy (TBCT). However, it had previously only been available for adults. Objectives To develop and validate a version of the CD-Quest for teens (CD-Quest-T) aged 11 to 17 years and test its psychometric properties. Method A total of 299 schoolchildren participated in the investigation. After content validity was assessed, the language was adapted for the target age group, and the length of the instrument was reduced to eight items (from the initial 15). Five cognitive therapists analyzed the content and structure of the items. Finally, to investigate the construct validity of the CD-Quest-T, the instrument was divided into a full scale and two subscales, which measure the frequency of the distortions and the intensity attributed to them, respectively. Results The overall internal consistency of the scale was α = 0.77, whereas subscale indices were α = 0.75 for the frequency scale and α = 0.73 for the intensity scale. Results from exploratory factor analysis and concurrent validity analysis indicated that the CD-Quest-T items have good psychometric properties and generate scores reliably. Conclusion The psychometric properties of the CD-Quest-T demonstrate its adequacy for measurement of cognitive distortions in adolescents.

13.
Sensors (Basel) ; 22(23)2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36501863

RESUMO

Industry 4.0 concept has become a worldwide revolution that has been mainly led by the manufacturing sector. Continuous Process Industry is part of this global trend where there are aspects of the "fourth industrial revolution" that must be adapted to the particular context and needs of big continuous processes such as oil refineries that have evolved to control paradigms supported by sector-specific technologies where big volumes of operation-driven data are continuously captured from a plethora of sensors. The introduction of Artificial Intelligence techniques can overcome the current limitations of Advanced Control Systems (mainly MPCs) by providing better performance on highly non-linear and complex systems and by operating with a broader scope in terms of signals/data and sub-systems. Moreover, the state of the art of traditional PID/MPC based solutions is showing an asymptotic improvement that requires a disruptive approach in order to reach relevant improvements in terms of efficiency, optimization, maintenance, etc. This paper shows the key aspects in oil refineries to successfully adopt Big Data and Machine Learning solutions that can significantly improve the efficiency and competitiveness of continuous processes.


Assuntos
Inteligência Artificial , Indústrias , Big Data , Tecnologia , Aprendizado de Máquina
14.
JBJS Rev ; 10(6)2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35658089

RESUMO

¼: COVID-19 is a disease that is challenging science, health-care systems, and humanity. An astonishingly wide spectrum of manifestations of multi-organ damage, including musculoskeletal, can be associated with SARS-CoV-2. ¼: In the acute phase of COVID-19, fatigue, myalgia, and arthralgia are the most common musculoskeletal symptoms. ¼: Post-COVID-19 syndrome is a group of signs and symptoms that are present for >12 weeks. The associated musculoskeletal manifestations are fatigue, arthralgia, myalgia, new-onset back pain, muscle weakness, and poor physical performance. ¼: Data on COVID-19 complications are growing due to large absolute numbers of cases and survivors in these 2 years of the pandemic. Additional musculoskeletal manifestations encountered are falls by the elderly, increased mortality after hip fracture, reduced bone mineral density and osteoporosis, acute sarcopenia, rhabdomyolysis, Guillain-Barré syndrome, muscle denervation atrophy, fibromyalgia, rheumatological disease triggering, septic arthritis, adhesive capsulitis, myositis, critical illness myopathy, onset of latent muscular dystrophy, osteonecrosis, soft-tissue abscess, urticarial vasculitis with musculoskeletal manifestations, and necrotizing autoimmune myositis. ¼: A wide range of signs and symptoms involving the musculoskeletal system that affect quality of life and can result in a decrease in disability-adjusted life years. This powerful and unpredictable disease highlights the importance of multimodality imaging, continuing education, and multidisciplinary team care to support preventive measures, diagnosis, and treatment.


Assuntos
COVID-19 , Sistema Musculoesquelético , Miosite , Idoso , Artralgia/etiologia , COVID-19/complicações , Fadiga/complicações , Humanos , Mialgia/complicações , Miosite/complicações , Qualidade de Vida , SARS-CoV-2 , Síndrome de COVID-19 Pós-Aguda
15.
Ann Med ; 54(1): 1548-1560, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35635048

RESUMO

Chronic liver disease (CLD), manifested as hepatic injury, is a major cause of global morbidity and mortality. CLD progresses to fibrosis, cirrhosis, and-ultimately-hepatocellular carcinoma (HCC) if left untreated. The different phenotypes of CLD based on their respective clinical features and causative agents include alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), metabolic-associated fatty liver disease (MAFLD), and drug-induced liver injury (DILI). The preferred treatment modality for CLD includes lifestyle modification and diet, along with limited pharmacological agents for symptomatic treatment. Moreover, oxidative stress (OS) is an important pathological mechanism underlying all CLD phenotypes; hence, the use of antioxidants to manage the disease is justified. Based on available clinical evidence, silymarin can be utilized as a hepatoprotective agent, given its potent antioxidant, antifibrotic, and anti-inflammatory properties. The role of silymarin in suppressing OS has been well established, and therefore silymarin is recommended for use in ALD and NAFLD in the guidelines approved by the Russian Medical Scientific Society of Therapists and the Gastroenterology Scientific Society of Russia. However, to discuss the positioning of the original silymarin in clinical guidelines and treatment protocols as a hepatoprotective agent for managing CLD concomitantly with other therapies, an expert panel of international and Russian medical professionals was convened on 11 November 2020. The panel reviewed approaches for the prevention and treatment of OS, existing guidelines for patient management for CLD, and available evidence on the effectiveness of silymarin in reducing OS, fibrosis, and hepatic inflammation and presented in the form of a narrative review. Key messagesAn expert panel of international and Russian medical professionals reviewed existing guidelines for ALD, NAFLD, MAFLD, and DILI to establish consensus recommendations that oxidative stress is the common pathophysiological mechanism underlying these conditions.The panel also discussed the positioning of original silymarin in clinical guidelines and treatment protocols as a hepatoprotective agent for managing CLD concomitantly with other therapies.The panel reviewed the effectiveness of 140 mg original silymarin three times a day in reducing oxidative stress in chronic liver diseases such as ALD, NAFLD, MAFLD, and DILI.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Silimarina , Antioxidantes/uso terapêutico , Humanos , Cirrose Hepática , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , Silimarina/farmacologia , Silimarina/uso terapêutico
16.
Pharmaceutics ; 15(1)2022 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-36678755

RESUMO

Redox-responsive and magnetic nanomaterials are widely used in tumor treatment separately, and while the application of their combined functionalities is perspective, exactly how such synergistic effects can be implemented is still unclear. This report investigates the internalization dynamics of magnetic redox-responsive nanoparticles (MNP-SS) and their cytotoxicity toward PC-3 and 4T1 cell lines. It is shown that MNP-SS synthesized by covalent grafting of polyethylene glycol (PEG) on the magnetic nanoparticle (MNP) surface via SS-bonds lose their colloidal stability and aggregate fully in a solution containing DTT, and partially in conditioned media, whereas the PEGylated MNP (MNP-PEG) without S-S linker control remains stable under the same conditions. Internalized MNP-SS lose the PEG shell more quickly, causing enhanced magnetic core dissolution and thus increased toxicity. This was confirmed by fluorescence microscopy using MNP-SS dual-labeled by Cy3 via labile disulfide, and Cy5 via a rigid linker. The dyes demonstrated a significant difference in fluorescence dynamics and intensity. Additionally, MNP-SS demonstrate quicker cellular uptake compared to MNP-PEG, as confirmed by TEM analysis. The combination of disulfide bonds, leading to faster dissolution of the iron oxide core, and the high-oxidative potential Fe3+ ions can synergically enhance oxidative stress in comparison with more stable coating without SS-bonds in the case of MNP-PEG. It decreases the cancer cell viability, especially for the 4T1, which is known for being sensitive to ferroptosis-triggering factors. In this work, we have shown the effect of redox-responsive grafting of the MNP surface as a key factor affecting MNP-internalization rate and dissolution with the release of iron ions inside cancer cells. This kind of synergistic effect is described for the first time and can be used not only in combination with drug delivery, but also in treatment of tumors responsive to ferroptosis.

17.
Front Bioeng Biotechnol ; 9: 728501, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34621729

RESUMO

Recently, the study of chitinases has become an important target of numerous research projects due to their potential for applications, such as biocontrol pest agents. Plant chitinases from carnivorous plants of the genus Drosera are most aggressive against a wide range of phytopathogens. However, low solubility or insolubility of the target protein hampered application of chitinases as biofungicides. To obtain plant chitinase from carnivorous plants of the genus Drosera in soluble form in E.coli expression strains, three different approaches including dialysis, rapid dilution, and refolding on Ni-NTA agarose to renaturation were tested. The developed « Rapid dilution ¼ protocol with renaturation buffer supplemented by 10% glycerol and 2M arginine in combination with the redox pair of reduced/oxidized glutathione, increased the yield of active soluble protein to 9.5 mg per 1 g of wet biomass. A structure-based removal of free cysteines in the core domain based on homology modeling of the structure was carried out in order to improve the soluble of chitinase. One improved chitinase variant (C191A/C231S/C286T) was identified which shows improved expression and solubility in E. coli expression systems compared to wild type. Computational analyzes of the wild-type and the improved variant revealed overall higher fluctuations of the structure while maintaining a global protein stability. It was shown that free cysteines on the surface of the protein globule which are not involved in the formation of inner disulfide bonds contribute to the insolubility of chitinase from Drosera capensis. The functional characteristics showed that chitinase exhibits high activity against colloidal chitin (360 units/g) and high fungicidal properties of recombinant chitinases against Parastagonospora nodorum. Latter highlights the application of chitinase from D. capensis as a promising enzyme for the control of fungal pathogens in agriculture.

18.
Cuad. Hosp. Clín ; 62(1): 46-50, jun. 2021. ilus
Artigo em Espanhol | LILACS | ID: biblio-1284307

RESUMO

La neuralgia del trigémino es un trastorno neuropático paroxístico que afecta a una o varias de las ramas sensoriales del nervio trigémino cuya etiología es variada, la más aceptada es por compresiones vasculares a nivel del ángulo ponto cerebeloso que generan conflicto de espacio. Dentro de las posibilidades de tratamiento, la descompresión microvascular permite la cura fisiopatológica de la neuralgia del trigémino, teniendo resultados satisfactorios a corto/largo plazo, y bastantes ventajas en comparación a otras técnicas de mínima invasión. Se presenta el caso de una paciente con tratamiento médico máximo no efectivo, a la cual se realizó descompresión microvascular evidenciando conflicto arterial y venoso con el nervio.


Trigeminal neuralgia is a paroxysmal neuropathic disorder that affects one or more of the sensory branches of the trigeminal nerve, the etiology of which is varied, the most accepted being due to vascular compressions at the level of the brainstem that generate conflict of space. Within the treatment possibilities, microvascular decompression allows the pathophysiological cure of trigeminal neuralgia, having satisfactory results in the short / long term, and many advantages compared to other minimally invasive techniques. We present the case of a patient with maximum ineffective medical treatment, who underwent microvascular decompression, showing arterial and venous conflict with the nerve.


Assuntos
Descompressão , Cirurgia de Descompressão Microvascular , Nervo Trigêmeo , Neuralgia do Trigêmeo
19.
Molecules ; 26(8)2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33919686

RESUMO

Cereal crops, such as oats and barley, possess a number of valuable properties that meet the requirements for functional diet components. This review summarized the available information about bioactive compounds of oat and barley grain. The results of studying the structure and physicochemical properties of the cell wall polysaccharides of barley and oat are presented. The main components of the flavonoids formation pathway are shown and data, concerning anthocyanins biosynthesis in various barley tissues, are discussed. Moreover, we analyzed the available information about structural and regulatory genes of anthocyanin biosynthesis in Hordeum vulgare L. genome, including ß-glucan biosynthesis genes in Avena sativa L species. However, there is not enough knowledge about the genes responsible for biosynthesis of ß-glucans and corresponding enzymes and plant polyphenols. The review also covers contemporary studies about collections of oat and barley genetic resources held by the N.I. Vavilov All-Russian Institute of Plant Genetic Resources (VIR). This review intended to provide information on the processes of biosynthesis of biologically active compounds in cereals that will promote further researches devoted to transcription factors controlling expression of structural genes and their role in other physiological processes in higher plants. Found achievements will allow breeders to create new highly productive varieties with the desirable properties.


Assuntos
Avena/química , Grão Comestível/química , Alimento Funcional , Hordeum/química , Compostos Fitoquímicos/análise , Melhoramento Vegetal , Avena/genética , Hordeum/genética
20.
Fuel (Lond) ; 284: 119024, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32863405

RESUMO

Waste cooking oil (WCO) is a valuable feedstock for the synthesis of biodiesel but the product exhibits poor oxidative stability. Techniques available for assessing this parameter are generally expensive and time-consuming, hence the purpose of this study was to develop and validate a rapid and reliable predictive system based on signals from the sensors of a commercial hand-held e-nose instrument. Biodiesels were synthesized from soybean oil and six samples of WCO, and their physicochemical characteristics and oxidative stabilities determined before and after storage in different types of containers for 30 or 60 days at room temperature or 43 °C. Linear regression models were constructed based on principal component analysis of the signals generated by all 32 e-nose sensors and stochastic modeling of signal profiles from individual sensors. The regression model with principal components as predictors was unable to explain the oxidative stability of biodiesels, while the regression model with stochastic parameters (combining signals from 11 sensors) as predictors showed an excellent goodness of fit (R2 = 0.91) with a 45-sample training set and a good quality of prediction (R2 = 0.84) with a 18-sample validation set. The proposed e-nose system was shown to be accurate and efficient and could be used to advantage by producers/distributors of biodiesel in the assessment fuel quality.

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