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1.
Arterioscler Thromb Vasc Biol ; 44(1): 124-142, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37942608

RESUMEN

BACKGROUND: Patients with constitutive activation of DNA-sensing pathway through stimulator of IFN (interferon) genes (STING), such as those with STING-associated vasculopathy with onset in infancy, develop pulmonary hypertension (PH). However, the role of STING signaling in general PH patients is heretofore undescribed. Here, we seek to investigate the role of STING in PH development. METHODS: STING expression in patient lung samples was examined. PH was induced in global STING-deficient mice and global type I IFN receptor 1-deficient mice using bleomycin or chronic hypoxia exposure. PH development was evaluated by right ventricular systolic pressure and Fulton index, with additional histological and flow cytometric analysis. VEGF (vascular endothelial growth factor) expression on murine immune cells was quantified and evaluated with multiplex and flow cytometry. Human myeloid-derived cells were differentiated from peripheral blood mononuclear cells and treated with either STING agonist or STING antagonist for evaluation of VEGF secretion. RESULTS: Global STING deficiency protects mice from PH development, and STING-associated PH seems independent of type I IFN signaling. Furthermore, a role for STING-VEGF signaling pathway in PH development was demonstrated, with altered VEGF secretion in murine pulmonary infiltrated myeloid cells in a STING-dependent manner. In addition, pharmacological manipulation of STING in human myeloid-derived cells supports in vivo findings. Finally, a potential role of STING-VEGF-mediated apoptosis in disease development and progression was illustrated, providing a roadmap toward potential therapeutic applications. CONCLUSIONS: Overall, these data provide concrete evidence of STING involvement in PH, establishing biological plausibility for STING-related therapies in PH treatment.


Asunto(s)
Hipertensión Pulmonar , Interferón Tipo I , Humanos , Animales , Ratones , Factor A de Crecimiento Endotelial Vascular , Hipertensión Pulmonar/genética , Leucocitos Mononucleares/metabolismo , Transducción de Señal , Interferón Tipo I/metabolismo
2.
J Biol Chem ; 299(4): 103056, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36822328

RESUMEN

Cationic and amphiphilic peptides can be used as homing devices to accumulate conjugated antibiotics to bacteria-enriched sites and promote efficient microbial killing. However, just as important as tackling bacterial infections, is the modulation of the immune response in this complex microenvironment. In the present report, we designed a peptide chimaera called Chim2, formed by a membrane-active module, an enzyme hydrolysis site and a formyl peptide receptor 2 (FPR2) agonist. This molecule was designed to adsorb onto bacterial membranes, promote their lysis, and upon hydrolysis by local enzymes, release the FPR2 agonist sequence for activation and recruitment of immune cells. We synthesized the isolated peptide modules of Chim2 and characterized their biological activities independently and as a single polypeptide chain. We conducted antimicrobial assays, along with other tests aiming at the analyses of the cellular and immunological responses. In addition, assays using vesicles as models of eukaryotic and prokaryotic membranes were conducted and solution structures of Chim2 were generated by 1H NMR. Chim2 is antimicrobial, adsorbs preferentially to negatively charged vesicles while adopting an α-helix structure and exposes its disorganized tail to the solvent, which facilitates hydrolysis by tryptase-like enzymes, allowing the release of the FPR2 agonist fragment. This fragment was shown to induce accumulation of the cellular activation marker, lipid bodies, in mouse macrophages and the release of immunomodulatory interleukins. In conclusion, these data demonstrate that peptides with antimicrobial and immunomodulatory activities can be considered for further development as drugs.


Asunto(s)
Antiinfecciosos , Receptores de Formil Péptido , Animales , Ratones , Antibacterianos/farmacología , Antiinfecciosos/química , Bacterias , Membranas , Receptores de Formil Péptido/antagonistas & inhibidores
3.
Anal Bioanal Chem ; 416(11): 2605-2623, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38099967

RESUMEN

Nanoparticle (NP) applications aiming to boost plant biomass production and enhance the nutritional quality of crops hae proven to be a valuable ally in enhancing agricultural output. They contribute to greater food accessibility for a growing and vulnerable population. These nanoscale particles are commonly used in agriculture as fertilizers, pesticides, plant growth promoters, seed treatments, opportune plant disease detection, monitoring soil and water quality, identification and detection of toxic agrochemicals, and soil and water remediation. In addition to the countless NP applications in food and agriculture, it is possible to highlight many others, such as medicine and electronics. However, it is crucial to emphasize the imperative need for thorough NP characterization beyond these applications. Therefore, analytical methods are proposed to determine NPs' physicochemical properties, such as composition, crystal structure, size, shape, surface charge, morphology, and specific surface area, detaching the inductively coupled plasma mass spectrometry (ICP-MS) that allows the reliable elemental composition quantification mainly in metallic NPs. As a result, this review highlights studies involving NPs in agriculture and their consequential effects on plants, with a specific focus on analyses conducted through ICP-MS. Given the numerous applications of NPs in this field, it is essential to address their presence and increase in the environment and humans since biomagnification and biotransformation effects are studies that should be further developed. In light of this, the demand for rapid, innovative, and sensitive analytical methods for the characterization of NPs remains paramount.


Asunto(s)
Nanopartículas del Metal , Nanopartículas , Humanos , Espectrometría de Masas/métodos , Plantas Comestibles , Nanopartículas/química , Productos Agrícolas , Suelo , Nanopartículas del Metal/química
4.
J Environ Manage ; 365: 121381, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38917546

RESUMEN

Present and future climatic trends are expected to markedly alter water fluxes and stores in the hydrologic cycle. In addition, water demand continues to grow due to increased human use and a growing population. Sustainably managing water resources requires a thorough understanding of water storage and flow in natural, agricultural, and urban ecosystems. Measurements of stable isotopes of water (hydrogen and oxygen) in the water cycle (atmosphere, soils, plants, surface water, and groundwater) can provide information on the transport pathways, sourcing, dynamics, ages, and storage pools of water that is difficult to obtain with other techniques. However, the potential of these techniques for practical questions has not been fully exploited yet. Here, we outline the benefits and limitations of potential applications of stable isotope methods useful to water managers, farmers, and other stakeholders. We also describe several case studies demonstrating how stable isotopes of water can support water management decision-making. Finally, we propose a workflow that guides users through a sequence of decisions required to apply stable isotope methods to examples of water management issues. We call for ongoing dialogue and a stronger connection between water management stakeholders and water stable isotope practitioners to identify the most pressing issues and develop best-practice guidelines to apply these techniques.

5.
Beilstein J Org Chem ; 20: 1167-1178, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38887581

RESUMEN

We describe the use of bismuth(III) triflate as an efficient and environmentally friendly catalyst for the Nazarov reaction of aryl vinyl ketones, leading to the synthesis of 3-aryl-2-ethoxycarbonyl-1-indanones and 3-aryl-1-indanones. By changing the temperature and reaction time, it was possible to modulate the reactivity, allowing the synthesis of two distinct product classes (3-aryl-2-ethoxycarbonyl-1-indanones and 3-aryl-1-indanones) in good to excellent yield. The reaction did not require additives and was insensitive to both air and moisture. Preliminary biological evaluation of some indanones showed a promising profile against some human cancer line cells.

6.
Crit Rev Microbiol ; : 1-22, 2023 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-37897442

RESUMEN

Helicobacter pylori is a gram-negative, spiral-shaped, flagellated bacterium that colonizes the stomach of half the world's population. Helicobacter pylori infection causes pathologies of varying severity. Standard oral therapy fails in 15-20% since the barriers of the oral route decrease the bioavailability of antibiotics and the intrinsic factors of bacteria increase the rates of resistance. Nanoparticles and microparticles are promising strategies for drug delivery into the gastric mucosa and targeting H. pylori. The variety of building blocks creates systems with distinct colloidal, surface, and biological properties. These features improve drug-pathogen interactions, eliminate drug depletion and overuse, and enable the association of multiple actives combating H. pylori on several fronts. Nanoparticles and microparticles are successfully used to overcome the barriers of the oral route, physicochemical inconveniences, and lack of selectivity of current therapy. They have proven efficient in employing promising anti-H. pylori compounds whose limitation is oral route instability, such as some antibiotics and natural products. However, the current challenge is the applicability of these strategies in clinical practice. For this reason, strategies employing a rational design are necessary, including in the development of nano- and microsystems for the oral route.

7.
BMC Public Health ; 23(1): 221, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36726116

RESUMEN

BACKGROUND: In front of the physical and social isolation, as well as feelings of fear and instability imposed by the pandemic of COVID-19, especially for risk groups such as people 50 + , it became even more relevant to discuss the formulation of personal plans for this age population. This study aimed to analyse the individual plans of people 50 + , considering their perception, feelings and life experiences during the COVID-19 pandemic. METHODS: This is a mixed study (quali-quantitative), using Minayo's methodology for content analysis and frequency analyses, made with 39 participants from the University of Brasília Educational Program, Universidade do Envelhecer - UniSER/UnB. We used a word cloud system and a wheel of life tool to showcase the results. RESULTS: Analysing professional achievements and situations participants want to overcome, the categories of feelings that stand out were Loving Relationships, Sadness, Family Absence, Grief, Trauma and Regret. Intellectual Development, Personal Fulfilment, Purpose and Creativity, Hobbies and Fun were the most mentioned personal plans displayed by the wheel of life. The key personal changes mentioned were to be less shy, prioritise themselves, change how they interact with others, and focus on their health. CONCLUSIONS: This study concludes that perception, feelings and life experiences during the COVID-19 pandemic did not seem to directly affect the path in elaborating personal plans.


Asunto(s)
COVID-19 , Humanos , COVID-19/epidemiología , Brasil/epidemiología , Pandemias , Emociones , Miedo
8.
Molecules ; 28(9)2023 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-37175359

RESUMEN

Breast cancer is the most common type of cancer and the leading cause of cancer mortality among women worldwide. Considering the limitations of the current treatments available, we analyzed the in vitro cytotoxic potential of ((4-Fluoro-phenyl)-{2-[(1-phenyl-9H-ß-carboline-3-carbonyl)-amino]-ethylamino}-methyl)-phosphonic acid dibutyl ester (BCP-1) in breast cancer cells (MCF-7 and MDA-MB-231) and in a non-tumor breast cell line (MCF-10A). BCP-1 has an α-aminophosphonate unit linked to the ß-carboline nucleus, and the literature indicates that compounds of these classes have high biological potential. In the present study, the mechanism of action of BCP-1 was investigated through methods of spectrofluorimetry, flow cytometry, and protein expression analysis. It was found that BCP-1 inhibited the proliferation of both cancer cell lines. Furthermore, it induced oxidative stress and cell cycle arrest in G2/M. Upregulation of apoptosis-related proteins such as Bax, cytochrome C, and caspases, as well as a decrease in the anti-apoptotic protein Bcl-2, indicated potential induction of apoptosis in the MDA-MB-231 cells. While in MCF-7 cells, BCP-1 activated the autophagic death pathway, which was demonstrated by an increase in autophagic vacuoles and acidic organelles, in addition to increased expression of LC3I/LC3II and reduced SQSTM1/p62 expression. Further, BCP-1 demonstrated antimetastatic potential by reducing MMP-9 expression and cell migration in both breast cancer cell lines. In conclusion, BCP-1 is a promising candidate for breast cancer chemotherapy.


Asunto(s)
Antineoplásicos , Neoplasias de la Mama , Femenino , Humanos , Neoplasias de la Mama/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Puntos de Control del Ciclo Celular , Células MCF-7 , Apoptosis , Proteínas Reguladoras de la Apoptosis , Carbolinas/farmacología , Proliferación Celular , Línea Celular Tumoral
10.
Trop Anim Health Prod ; 54(6): 364, 2022 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-36316411

RESUMEN

The objective of this study was to examine the effect of increasing levels of red propolis extract (RPE) on the intake, digestibility, feeding behavior, rumen parameters, metabolic parameters, and performance of feedlot lambs. Thirty-five uncastrated male Santa Inês lambs with an initial weight of 17.08 ± 2.36 kg were used in a completely randomized design with five treatments (0, 7, 14, 21, or 28 mL RPE/animal/day). The animals were confined for 68 days. Red propolis extract induced a negative quadratic response (P < 0.05) in the intakes of dry matter, organic matter, crude protein, ether extract, neutral detergent fiber, non-fibrous carbohydrates, and metabolizable energy. The apparent digestibility coefficients of dry matter, organic matter, and neutral detergent fiber, as well as the rumen concentration of NH3-N, also responded quadratically (P < 0.05) to RPE. Feeding efficiency increased linearly (P < 0.05) with the inclusion of RPE, whereas rumination efficiency was maximum (P < 0.05) at the RPE level of 16 mL/day. Red propolis extract induced a linear response (P < 0.05) in serum total protein, albumin, creatinine, and gamma-glutamyl transpeptidase. There was a quadratic effect on final body weight and average daily gain with minimum values for inclusion of RPE of 12.89 mL/day and 10.93 mL/day respectively. Feed efficiency rose linearly (P < 0.05) with the increasing concentrations of RPE in the diet. The inclusion of 21 mL RPE/day (8.5 mg total flavonoids/mL) in the diet of feedlot lambs is recommended to reduce the rumen NH3-N production and increase the animals' performance.


Asunto(s)
Própolis , Rumen , Ovinos , Animales , Masculino , Rumen/metabolismo , Digestión , Detergentes/metabolismo , Detergentes/farmacología , Fibras de la Dieta/metabolismo , Dieta/veterinaria , Extractos Vegetales/farmacología , Alimentación Animal/análisis
11.
Trop Anim Health Prod ; 54(6): 379, 2022 Nov 12.
Artículo en Inglés | MEDLINE | ID: mdl-36370198

RESUMEN

This study aimed to evaluate the effect of the inclusion of coconut fruit pulp by-product (CPB) on the intake, apparent digestibility, nitrogen balance, and ruminal parameters of sheep. Five intact, male, non-descript lambs with a mean initial body weight of 25.5 ± 1.68 kg were assigned to a Latin square design (5 × 5) of five treatments consisting of CPB inclusion levels, in five proportions of 0%, 5%, 10%, 15%, and 20% dry matter (DM), in diets consisting of sugarcane bagasse as forage, with corn and soybean meal. Each period lasted 15 days for adaptation followed by 6 days for data collection. The inclusion of CPB linearly decreased (P < 0.05) the intake of DM, crude protein, non-fibre carbohydrates, neutral detergent fibre (NDF), and DM digestibility. The inclusion of CPB linearly increased (P < 0.05) the ether extract digestibility, but did not influence (P > 0.05) the NDF digestibility. There was a linear reduction (P < 0.05) in the absorbed nitrogen (N) and retained N (g/day); however, a quadratic increase (P < 0.05) for N absorbed (% consumed) as well as ammonia nitrogen was observed. There was a quadratic increase (P < 0.05) for propionate (mMol/L and %) and the ratio of acetate, propionate and butyrate (mMol/L and %) with the inclusion of CPB in the diet. Based on these findings, it was recommended to incorporate CPB up to the level of 5% in the diet of sheep.


Asunto(s)
Rumen , Saccharum , Ovinos , Animales , Masculino , Rumen/metabolismo , Celulosa/metabolismo , Cocos/metabolismo , Digestión , Frutas , Propionatos/metabolismo , Fermentación , Dieta/veterinaria , Fibras de la Dieta/metabolismo , Nitrógeno/metabolismo , Alimentación Animal/análisis
12.
Gen Dent ; 70(3): 46-50, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35467543

RESUMEN

The aim of this study was to measure the angular and linear deviations between planned and placed dental implant positions at different depths in an in vitro model. Ten dental manikins of a maxilla without the central and lateral incisors were used. The implants were placed in the tooth positions using a prototype guide based on computed tomographic scans of dental casts. The groups consisted of implants placed at varying depths according to tooth position: 1 mm deep for the right lateral incisor, 2 mm deep for the right central incisor, 3 mm deep for the left central incisor, and 4 mm deep for the left lateral incisor (n = 10 per group). After implant placement, the manikin was scanned again to compare the positioning of the implants to the planned positions. Statistical analysis evaluated the linear deviations between planned and placed implant positions at 3 points (coronal, central, and apical) as well as the angular discrepancies. The analysis showed that the depth of the implant placement proportionally affected the linear deviation of the actual position from the planned position; thus, the deeper implants showed significantly greater linear deviations (P < 0.05; 1-way analysis of variance and Tukey test). There were no statistically significant differences in the mean angular deviations of the groups. Thus, the results suggest that implants placed at greater depths present greater linear deviations than implants placed at shallower depths, but the angular deviation is not affected by implant depth.


Asunto(s)
Implantes Dentales , Cirugía Asistida por Computador , Tomografía Computarizada de Haz Cónico , Implantación Dental Endoósea/métodos , Humanos , Imagenología Tridimensional , Incisivo , Cirugía Asistida por Computador/métodos
13.
Am J Physiol Regul Integr Comp Physiol ; 321(3): R513-R521, 2021 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-34346721

RESUMEN

Experiments aimed to evaluate the tissue distribution of Mas-related G protein-coupled receptor D (MrgD) revealed the presence of immunoreactivity for the MrgD protein in the rostral insular cortex (rIC), an important area for autonomic and cardiovascular control. To investigate the relevance of this finding, we evaluated the cardiovascular effects produced by the endogenous ligand of MrgD, alamandine, in this brain region. Mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) were recorded in urethane anesthetized rats. Unilateral microinjection of equimolar doses of alamandine (40 pmol/100 nL), angiotensin-(1-7), angiotensin II, angiotensin A, and Mas/MrgD antagonist d-Pro7-Ang-1-7 (50 pmol/100 nL), Mas antagonist A779 (100 pmol/100 nL), or vehicle (0.9% NaCl) were made in different rats (n = 4-6/group) into rIC. To verify the specificity of the region, a microinjection of alamandine was also performed into intermediate insular cortex (iIC). Microinjection of alamandine in rIC produced an increase in MAP (Δ = 15 ± 2 mmHg), HR (Δ = 36 ± 4 beats/min), and RSNA (Δ = 31 ± 4%), but was without effects at iIC. Strikingly, an equimolar dose of angiotensin-(1-7) at rIC did not produce any change in MAP, HR, and RSNA. Angiotensin II and angiotensin A produced only minor effects. Alamandine effects were not altered by A-779, a Mas antagonist, but were completely blocked by the Mas/MrgD antagonist d-Pro7-Ang-(1-7). Therefore, we have identified a brain region in which alamandine/MrgD receptor but not angiotensin-(1-7)/Mas could be involved in the modulation of cardiovascular-related neuronal activity. This observation also suggests that alamandine might possess unique effects unrelated to angiotensin-(1-7) in the brain.


Asunto(s)
Angiotensina I/farmacología , Presión Arterial/efectos de los fármacos , Sistema Cardiovascular/inervación , Corteza Cerebral/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Riñón/inervación , Proteínas del Tejido Nervioso/agonistas , Oligopéptidos/farmacología , Fragmentos de Péptidos/farmacología , Receptores Acoplados a Proteínas G/agonistas , Sistema Nervioso Simpático/efectos de los fármacos , Animales , Corteza Cerebral/fisiología , Ligandos , Masculino , Microinyecciones , Proteínas del Tejido Nervioso/metabolismo , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas/agonistas , Proteínas Proto-Oncogénicas/metabolismo , Ratas Sprague-Dawley , Receptores Acoplados a Proteínas G/metabolismo , Sistema Nervioso Simpático/fisiología
14.
Circ Res ; 124(5): 727-736, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30612527

RESUMEN

RATIONALE: Increased microglial activation and neuroinflammation within autonomic brain regions have been implicated in sustained hypertension, and their inhibition by minocycline-an anti-inflammatory antibiotic-produces beneficial effects. These observations led us to propose a dysfunctional brain-gut communication hypothesis for hypertension. However, it has been difficult to reconcile whether an anti-inflammatory or antimicrobial action is the primary beneficial effect of minocycline in hypertension. Accordingly, we utilized chemically modified tetracycline-3 (CMT-3)-a derivative of tetracycline that has potent anti-inflammatory activity-to address this question. OBJECTIVE: Test the hypothesis that central administration of CMT-3 would inhibit microglial activation, attenuate neuroinflammation, alter selective gut microbial communities, protect the gut wall from developing hypertension-associated pathology, and attenuate hypertension. METHODS AND RESULTS: Rats were implanted with radiotelemetry devices for recording mean arterial pressure. Ang II (angiotensin II) was infused subcutaneously using osmotic mini-pumps to induce hypertension. Another osmotic mini-pump was surgically implanted to infuse CMT-3 intracerebroventricularly. Intracerebroventricular CMT- 3 infusion was also investigated in SHR (spontaneously hypertensive rats). Physiological, pathological, immunohistological parameters, and fecal microbiota were analyzed. Intracerebroventricular CMT-3 significantly inhibited Ang II-induced increases in number of microglia, their activation, and proinflammatory cytokines in the paraventricular nucleus of hypothalamus. Further, intracerebroventricular CMT-3 attenuated increased mean arterial pressure, normalized sympathetic activity, and left ventricular hypertrophy in Ang II rats, as well as in the SHR. Finally, CMT-3 beneficially restored certain gut microbial communities altered by Ang II and attenuated pathological alterations in gut wall. CONCLUSIONS: These observations demonstrate that inhibition of microglial activation alone was sufficient to induce significant antihypertensive effects. This was associated with unique changes in gut microbial communities and profound attenuation of gut pathology. They suggest, for the first time, a link between microglia and certain microbial communities that may have implications for treatment of hypertension.


Asunto(s)
Antihipertensivos/administración & dosificación , Microbioma Gastrointestinal/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Intestinos/efectos de los fármacos , Microglía/efectos de los fármacos , Núcleo Hipotalámico Paraventricular/efectos de los fármacos , Tetraciclinas/administración & dosificación , Angiotensina II , Animales , Antibacterianos/administración & dosificación , Antiinflamatorios/administración & dosificación , Presión Arterial/efectos de los fármacos , Sistema Nervioso Autónomo/efectos de los fármacos , Sistema Nervioso Autónomo/fisiopatología , Modelos Animales de Enfermedad , Hipertensión/microbiología , Hipertensión/patología , Hipertensión/fisiopatología , Infusiones Intraventriculares , Intestinos/inervación , Intestinos/microbiología , Intestinos/patología , Masculino , Microglía/patología , Núcleo Hipotalámico Paraventricular/patología , Núcleo Hipotalámico Paraventricular/fisiopatología , Ratas Endogámicas SHR , Ratas Endogámicas WKY
15.
Trop Anim Health Prod ; 53(5): 472, 2021 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-34550484

RESUMEN

The aim of the present study was to evaluate whether the addition of red propolis extract (RPE), in different roughage: concentrate (R:C) ratios, influences the intake, digestibility, ruminal parameters, and serum biochemistry of sheep. We used eight Santa Inês sheep with an average body weight of 29.45 ± 1.58 kg, housed in metabolism cages for 60 days, and distributed in two simultaneous Latin square designs in a 2 × 2 factorial scheme. The factors consisted of two R:C ratios (70:30 and 30:70) with or without the addition of 15 mL/day of RPE. No interactions were found (P > 0.05) between R:C ratios and with or without RPE. Sheep fed 30:70 ratio showed higher (P < 0.05) intake and dry matter (DM) digestibility and non-fibrous carbohydrates and lower (P < 0.05) intake and neutral detergent fiber (NDF) digestibility. The addition of RPE did not influence (P > 0.05) the intake or nutrients digestibility, but the sheep that received RPE had a higher (P < 0.05) ruminal pH and longer (P < 0.05) time of rumination (min/kg DM) compared to the group without propolis. The ruminal ammonia concentration was higher for sheep fed 70:30 ratio, but the concentrations of total protein and albumin did not differ between R:C ratios. The addition of 15 mL of RPE does not influence the intake, digestibility, ingestive behavior, and rumen ammonical nitrogen of sheep. There is no association between the R:C ratio and the addition of 15 mL/day of RPE for sheep.


Asunto(s)
Fibras de la Dieta , Própolis , Alimentación Animal/análisis , Animales , Dieta/veterinaria , Digestión , Extractos Vegetales , Própolis/farmacología , Ovinos , Oveja Doméstica
16.
Physiol Genomics ; 52(3): 121-132, 2020 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-31869283

RESUMEN

Fecal matter transfer from hypertensive patients and animals into normotensive animals increases blood pressure, strengthening the evidence for gut-microbiota interactions in the control of blood pressure. However, cellular and molecular events involved in gut dysbiosis-associated hypertension remain poorly understood. Therefore, our objective in this study was to use gene expression profiling to characterize the gut epithelium layer in the colon in hypertension. We observed significant suppression of components of T cell receptor (TCR) signaling in the colonic epithelium of spontaneously hypertensive rats (SHR) when compared with Wistar Kyoto (WKY) normotensive rats. Western blot analysis confirmed lower expression of key proteins including T cell surface glycoprotein CD3 gamma chain (Cd3g) and lymphocyte cytosolic protein 2 (Lcp2). Furthermore, lower expression of cytokines and receptors responsible for lymphocyte proliferation, differentiation, and activation (e.g., Il12r, Il15ra, Il7, Il16, Tgfb1) was observed in the colonic epithelium of the SHR. Finally, Alpi and its product, intestinal alkaline phosphatase, primarily localized in the epithelial cells, were profoundly lower in the SHR. These observations demonstrate that the colonic epithelium undergoes functional changes linked to altered immune, barrier function, and dysbiosis in hypertension.


Asunto(s)
Colon/metabolismo , Microbioma Gastrointestinal/genética , Hipertensión/metabolismo , Mucosa Intestinal/metabolismo , Transcriptoma , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Fosfatasa Alcalina/metabolismo , Animales , Presión Sanguínea , Complejo CD3/metabolismo , Citocinas/metabolismo , Disbiosis , Isoenzimas/metabolismo , Masculino , Fosfoproteínas/metabolismo , RNA-Seq , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Receptores de Antígenos de Linfocitos T/metabolismo
17.
Protein Expr Purif ; 170: 105596, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32036001

RESUMEN

Antibodies that block interaction of immune checkpoint receptors with its ligands have revolutionized the treatment of several cancers. Despite the success of this approach, the high cost has been restricted the use of this class of drugs. In this context, the development of biosimilar can be an important strategy for reducing prices and expanding access after patent has been dropped. Here, we evaluated the use of HEK293 cells for transient expression of an immune checkpoint-blocking antibody as a first step for biosimilar development. Antibody light and heavy chain genes were cloned into pCI-neo vector and transiently expressed in HEK293 cells. The culture supernatant was then subjected to protein A affinity chromatography, which allowed to obtain the antibody with high homogeneity. For physicochemical comparability, biosimilar antibody and reference drug were analyzed by SDS-PAGE, isoelectric focusing, circular dichroism and fluorescence spectroscopy. The results indicated that the both antibodies have a high degree of structural similarity. Lastly, the biosimilar antibody binding capacity to target receptor was shown to be similar to reference product in ELISA and flow cytometry assays. These data demonstrate that the HEK293 system can be used as an important tool for candidate selection and early development of biosimilar antibodies.


Asunto(s)
Anticuerpos Monoclonales/farmacología , Biosimilares Farmacéuticos/farmacología , Inhibidores de Puntos de Control Inmunológico/farmacología , Proteínas de Punto de Control Inmunitario/genética , Cadenas Pesadas de Inmunoglobulina/farmacología , Cadenas Ligeras de Inmunoglobulina/farmacología , Anticuerpos Monoclonales/biosíntesis , Afinidad de Anticuerpos , Especificidad de Anticuerpos , Biosimilares Farmacéuticos/metabolismo , Cromatografía de Afinidad , Vectores Genéticos/química , Vectores Genéticos/metabolismo , Células HEK293 , Humanos , Inhibidores de Puntos de Control Inmunológico/inmunología , Proteínas de Punto de Control Inmunitario/inmunología , Cadenas Pesadas de Inmunoglobulina/biosíntesis , Cadenas Ligeras de Inmunoglobulina/biosíntesis , Focalización Isoeléctrica
18.
Pharmacol Res ; 151: 104518, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31730803

RESUMEN

Pulmonary hypertension (PH) is classically considered a disease of pulmonary vasculature which has been the predominant target for drug development and PH therapy. Despite significant advancement in recent years in identification of new drug targets and innovative treatment strategies, the prognosis of PH remains poor, with median survival of 5 years. Recent studies have demonstrated involvement of neuroinflammation, altered autonomic and gastrointestinal functions and increased trafficking of bone marrow-derived cells in cardiopulmonary pathophysiology. This has led to the proposal that PH could be considered a systemic disease involving complex interactions among many organs. Our objectives in this review is to summarize evidence for the involvement of the brain, bone marrow and gut in PH pathophysiology. Then, to synthesize all evidence supporting a brain-gut-lung interaction hypothesis for consideration in PH pathophysiology and finally to summarize unanswered questions and future directions to move this novel concept forward. This forward-thinking view, if proven by further experiments, would provide new opportunities and novel targets for the control and treatment of PH.


Asunto(s)
Hipertensión Pulmonar/complicaciones , Hipertensión Pulmonar/fisiopatología , Pulmón/fisiopatología , Animales , Médula Ósea/fisiopatología , Encéfalo/fisiopatología , Microbioma Gastrointestinal , Tracto Gastrointestinal/fisiopatología , Humanos , Inflamación/complicaciones , Inflamación/fisiopatología , Sistema Renina-Angiotensina
19.
Dermatol Ther ; 33(6): e13926, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32779817

RESUMEN

Coronavirus disease (COVID-19) became pandemic since this is a disease with a high infection rate. The study's object is to identify clinical and histopathological findings of cutaneous manifestations of COVID-19 patients. The evidence was analyzed in PubMed, CINAHL, Cochrane, Web of Science, and Scopus, with the search strategy (covid 19 OR covid-19 OR corona OR coronavirus OR sars-cov-2) AND (cutaneous or cutaneous manifestations OR), and 17 studies were included, involving 351 cases with COVID19 and skin manifestations. The lesions were classified mainly as maculopapular, erythematous, vesicular, and urticarial. Histopathological analyses suggest a predominance of spongiosis, perivascular infiltrate of lymphocytes, and thrombogenic vasculopathy.


Asunto(s)
COVID-19/complicaciones , Enfermedades Cutáneas Virales/epidemiología , Humanos , Enfermedades Cutáneas Virales/patología , Enfermedades Cutáneas Virales/virología
20.
Molecules ; 25(23)2020 Nov 26.
Artículo en Inglés | MEDLINE | ID: mdl-33256223

RESUMEN

This study evaluated the effect of Mucuna pruriens (MP) administration on neuroinflammation and behavioral and murinometric parameters in obese rats. Proximate composition, oligosaccharide and phenolic compound profile of MP were determined. Wistar adult male rats were randomized into healthy (HG) and obese group (OG). The HG consumed a control chow diet while OG consumed a cafeteria diet for eight weeks. Then, they were subdivided into: Healthy (HG); Healthy with MP administration (HGMP); Obese (OG); Obese with MP administration (OGMP), with the consumption of the respective diets remaining for another eight weeks, in addition to gavage with MP extract to supplemented groups (750 mg/kg weight). MP presented a composition rich in proteins and phenolic compounds, especially catechin, in addition to 1-kestose and levodopa. Supplementation reduced food intake, body weight, and thoracic and abdominal circumferences in obese rats. MP showed anxiolytic and antidepressant effects and reduced morphological damage and expression of interleukin 6 in the hippocampus of obese rats. MP treatment showed satietogenic, slimming, anxiolytic and antidepressant effects, besides to minimizing hippocampal neuroinflammation in obese rats. Our results demonstrated the potential anti-obesity of MP which are probably related to the high content of bioactive compounds present in this plant extract.


Asunto(s)
Ansiolíticos/farmacología , Antidepresivos/química , Antidepresivos/farmacología , Mucuna/química , Extractos Vegetales/farmacología , Animales , Ansiolíticos/administración & dosificación , Ansiolíticos/química , Antidepresivos/administración & dosificación , Conducta Animal/efectos de los fármacos , Modelos Animales de Enfermedad , Histocitoquímica , Inmunohistoquímica/métodos , Obesidad , Fitoquímicos/química , Fitoquímicos/farmacología , Fitoterapia , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Ratas
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