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The modified release of active substances such as chlorzoxazone from matrix tablets, based on Kollidon®SR and chitosan, depends both on the drug solubility in the dissolution medium and on the matrix composition. The aim of this study is to obtain some new oral matrix tablet formulations, based on Kollidon®SR and chitosan, in order to optimize the low-dose oral bioavailability of chlorzoxazone, a non-steroidal anti-inflammatory drug of class II Biopharmaceutical Classification System. Nine types of chlorzoxazone matrix tablets were obtained using the direct compression method by varying the components ratio as 1:1, 1:2, and 1:3 chlorzoxazone/excipients, 20-40 w/w % Kollidon®SR, 3-7 w/w % chitosan while the auxiliary substances: Aerosil® 1 w/w %, magnesium stearate 0.5 w/w % and Avicel® up to 100 w/w % were kept in constant concentrations. Pharmaco-technical characterization of the tablets included the analysis of flowability and compressibility properties (flow time, friction coefficient, angle of repose, Hausner ratio, and Carr index), and pharmaco-chemical characteristics (such as mass and dose uniformity, thickness, diameter, mechanical strength, friability, softening degree, and in vitro release profiles). Based on the obtained results, only three matrix tablet formulations (F1b, F2b, and F3b, containing 30 w/w % KOL and 5 w/w % CHT, were selected and further tested. These formulations were studied in detail by Fourier-transform infrared spectrometry, X-ray diffraction, thermogravimetry, and differential scanning calorimetry. The three formulations were comparatively studied regarding the release kinetics of active substances using in vitro release testing. The results were analyzed by fitting into four representative mathematical models for the modified-release oral formulations. In vitro kinetic study revealed a complex mechanism of release occurring in two steps of drug release, the first step (0-2 h) and the second (2-36 h). Two factors were calculated to assess the release profile of chlorzoxazone: f1-the similarity factor, and f2-the factor difference. The results have shown that both Kollidon®SR and chitosan may be used as matrix-forming agents when combined with chlorzoxazone. The three formulations showed optima pharmaco-technical properties and in vitro kinetic behavior; therefore, they have tremendous potential to be used in oral pharmaceutical products for the controlled delivery of chlorzoxazone. In vitro dissolution tests revealed a faster drug release for the F2b sample.
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Quitosano , Clorzoxazona , Preparaciones de Acción Retardada , Liberación de Fármacos , Interacciones Hidrofóbicas e Hidrofílicas , Comprimidos , Comprimidos/química , Clorzoxazona/química , Clorzoxazona/farmacocinética , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacocinética , Quitosano/química , Solubilidad , Excipientes/química , Química Farmacéutica/métodosRESUMEN
The cause of death of Saint-Louis is not known, but recent findings indicated that he presented scurvy and inflammatory jaw disease, which has been associated with infection by oral commensals. Here, we have the exceptional opportunity to analyze the relics of the viscera of King Saint-Louis. A 4.3 g sample from the viscera relics of King Saint-Louis conserved in Versailles' cathedral was subjected to radiocarbon dating, electronic and optic microscopy, and elementary, palynological, molecular, proteomics and microbiological analyses including specific PCR and v3v4 16 S rRNA gene amplification prior to large-scale sequencing using an Illumina MiSeq instrument. The measured radiocarbon age was Cal 1290 CE-1400, which was compatible with that of the viscera of St Louis viscera, considering the addition of lime, incense and vegetables within the human organs. Elemental and palynological analyses confirmed a medieval embalming process. Proteomics analysis identified mainly human muscle and blood proteins. Specific PCR for plague, amoebiasis, shigellosis and typhoid fever was negative. C. sputigena was identified as the main pathogenic species representing 10.8 % of all microbial sequences. In contrast, C. sputigena was found in only 0.001 % of samples sequenced in our center, and the 23 positive human samples showed a dramatically lower abundance (0.02-2.6 %). In the literature, human infections with C. sputigena included odontitis, dental abscess, sinusitis, thoracic infections and bacteremia, particularly in immunocompromised patients with oral and dental diseases consistent with recent analysis of King Saint-Louis' jaw. C. sputigena, a commensal of the mouth that is potentially pathogenic and responsible for fatal bacteremia, may have been the cause of the king's death.
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Bacteriemia , Escorbuto , Masculino , Humanos , Causas de Muerte , Bacteriemia/microbiología , FranciaRESUMEN
CD11c+ T-bet+ B cells generated during ehrlichial infection require CD4+ T cell help and IL-21 signaling for their development, but the exact T cell subset required had not been known. In this study, we show in a mouse model of Ehrlichia muris that type 1 T follicular helper (TFH1) cells provide help to CD11c+ T-bet+ B cells via the dual secretion of IL-21 and IFN-γ in a CD40/CD40L-dependent manner. TFH1 cell help was delivered in two phases: IFN-γ signals were provided early in infection, whereas CD40/CD40L help was provided late in infection. In contrast to T-bet+ T cells, T-bet+ B cells did not develop in the absence of B cell-intrinsic Bcl-6 but were generated in the absence of T-bet. T-bet-deficient memory B cells were largely indistinguishable from their wild-type counterparts, although they no longer underwent switching to IgG2c. These data suggest that a primary function of T-bet in B cells during ehrlichial infection is to promote appropriate class switching, not lineage specification. Thus, CD11c+ memory B cells develop normally without T-bet but require Bcl-6 and specialized help from dual cytokine-producing TFH1 cells.
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Antígenos CD11/metabolismo , Interferón gamma/metabolismo , Interleucinas/metabolismo , Proteínas Proto-Oncogénicas c-bcl-6/metabolismo , Células T Auxiliares Foliculares/metabolismo , Proteínas de Dominio T Box/metabolismo , Animales , Linfocitos B/inmunología , Linfocitos B/metabolismo , Antígenos CD11/inmunología , Antígenos CD40/inmunología , Antígenos CD40/metabolismo , Ligando de CD40/inmunología , Ligando de CD40/metabolismo , Ehrlichia/inmunología , Ehrlichia/metabolismo , Femenino , Memoria Inmunológica/inmunología , Interferón gamma/inmunología , Interleucinas/inmunología , Ratones , Ratones Endogámicos C57BL , Proteínas Proto-Oncogénicas c-bcl-6/inmunología , Receptores de IgG/inmunología , Receptores de IgG/metabolismo , Células T Auxiliares Foliculares/inmunología , Proteínas de Dominio T Box/inmunologíaRESUMEN
Here, we describe the preparation and characterization of organic/inorganic hybrid polymer multifunctional nanocarriers. Novel nanocomposites of gold nanoparticles using pH-responsive coordination pentablock terpolymers of poly(ε-caprolactone)-b-poly(ethylene oxide)-b-poly(2-vinylpyridine)-b-poly(ethylene oxide)-b-poly(ε-caprolactone), bearing or not bearing partially quaternized vinylpyridine moieties, were studied. The template morphology of the coordination pentablock terpolymer at physiological pH ranges from crew-cut to multicompartmentalized micelles which can be tuned by chemical modification of the central block. Additionally, the presence of 2VP groups allows the coordination of gold ions, which can be reduced in situ to construct gold@polymer nanohybrids. Furthermore, the possibility of tuning the gold distribution in the micelles, through partial quaternization of the central P2VP block, was also investigated. Various morphological gold colloidal nanoparticles such as gold@core-corona nanoparticles and gold@core-gold@corona nanoparticles were synthesized on the corresponding template of the pentablock terpolymer, first by coordination with gold ions, followed by reduction with NaBH4. The pentablock and gold@pentablock nanoparticles could sparingly accommodate a water-soluble drug, Tamoxifen (TAX), in their hydrophobic micellar cores. The nanostructure of the nanocarrier remarkably affects the TAX delivery kinetics. Importantly, the hybrid gold@polymer nanoparticles showed prolonged release profiles for the guest molecule, relative to the corresponding bare amphiphilic pentablock polymeric micelles. These Gold@pentablock terpolymer hybrid nanoparticles could act as a multifunctional theranostic nanoplatform, integrating sustainable pH-controlled drug delivery, diagnostic function and photothermal therapy.
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Nanopartículas del Metal , Micelas , Oro/química , Cinética , Poliésteres/química , Polietilenglicoles/química , Polímeros/química , TamoxifenoRESUMEN
Bacterial, parasitic, and viral infections are well-known causes of lymphoid tissue disorganization, although the factors, both host and/or pathogen derived, that mediate these changes are largely unknown. Ehrlichia muris infection in mice causes a loss of germinal center (GC) B cells that is accompanied by the generation of extrafollicular T-bet+ CD11c+ plasmablasts and IgM memory B cells. We addressed a possible role for TNF-α in this process because this cytokine has been shown to regulate GC development. Ablation of TNF-α during infection resulted in an 8-fold expansion of GL7+ CD38lo CD95+ GC B cells, and a 2.5- and 5-fold expansion of CD138+ plasmablasts and T-bet+ memory cells, respectively. These changes were accompanied by a reduction in splenomegaly, more organized T and B cell zones, and an improved response to Ag challenge. CXCL13, the ligand for CXCR5, was detected at 6-fold higher levels following infection but was much reduced following TNF-α ablation, suggesting that CXCL13 dysregulation also contributes to loss of lymphoid tissue organization. T follicular helper cells, which also underwent expansion in infected TNF-α--deficient mice, may also have contributed to the expansion of T-bet+ B cells, as the latter are known to require T cell help. Our findings contrast with previously described roles for TNF-α in GCs and reveal how host-pathogen interactions can induce profound changes in cytokine and chemokine production that can alter lymphoid tissue organization, GC B cell development, and extrafollicular T-bet+ B cell generation.
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Linfocitos B/inmunología , Infecciones Bacterianas/inmunología , Centro Germinal/inmunología , Tejido Linfoide/fisiología , Factor de Necrosis Tumoral alfa/fisiología , Animales , Quimiocina CXCL13/fisiología , Tolerancia Inmunológica , Memoria Inmunológica , Tejido Linfoide/inmunología , Ratones , Ratones Endogámicos C57BLRESUMEN
Increasing interest on sustainable agriculture has led to the development of new materials which can be used as seed coating agents. In this study, a new material was developed based on gelatin film reinforced with cellulose nanocrystals (CNC) which was further used as nanocomposite matrix for Trichoderma harzianum KUEN 1585 spores. The nanocomposite films were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and scanning electron microscopy (SEM), showing the formation of new hydrogen bonds between the components with a good compatibility between them. Measurements of water contact angles and tests of water vapor sorption and swelling degree revealed an improvement in the water vapor absorption properties of the films as a result of their reinforcement with CNC. Furthermore, by adding the Trichoderma harzianum KUEN 1585 spp. in the seed coating material, the germination percentage, speed of germination and roots length of the corn seeds improved. The polymeric coating did not inhibit the growth of T. harzianum KUEN 1585, with this material being a good candidate in modern agriculture.
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Celulosa/química , Gelatina/química , Hypocreales/fisiología , Semillas/fisiología , Zea mays/fisiología , Germinación , Enlace de Hidrógeno , Microscopía Electrónica de Rastreo , Nanocompuestos/química , Nanocompuestos/microbiología , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos XRESUMEN
Around the world there are growing concerns for waste electrical and electronic equipment. This is motivated by the harmful effects of waste electrical and electronic equipment on the environment, but also by the perspectives of materials recovery. Differences between countries regarding waste electrical and electronic equipment management are notable in the European Union. Romania is among the countries that have made significant efforts to comply with European Union regulations, but failed reaching the collection target. The article presents a mini review of the waste electrical and electronic equipment management system in Romania, based on legislation and policy documents, statistical data, research studies and reports published by national and international organisations. The article debates subjects like legislative framework, the electrical and electronic equipment Romanian market, the waste electrical and electronic equipment collection system, waste electrical and electronic equipment processing and waste electrical and electronic equipment behaviour. The recast of the European directive brings new challenges to national authorities and to other stakeholders involved in the waste electrical and electronic equipment management. Considering the fact that Romania has managed a collection rate of roughly 1 kg capita(-1) in the last years, the new higher collection targets established by the waste electrical and electronic equipment Directive offer a serious challenge for the management system. Therefore, another aim of the article is to highlight the positive and negative aspects in the Romanian waste electrical and electronic equipment field, in order to identify the flows that should be corrected and the opportunities that could help improve this system to the point of meeting the European standards imposed by the European Directive.
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Residuos Electrónicos/análisis , Reciclaje/métodos , Administración de Residuos/métodos , Reciclaje/legislación & jurisprudencia , Reciclaje/estadística & datos numéricos , Eliminación de Residuos/legislación & jurisprudencia , Eliminación de Residuos/métodos , Eliminación de Residuos/estadística & datos numéricos , Rumanía , Administración de Residuos/legislación & jurisprudencia , Administración de Residuos/estadística & datos numéricosRESUMEN
In this work, the self-assembly behavior and pH responsiveness of a triblock copolypeptide in aqueous media are demonstrated. The copolypeptide was composed of a central pH responsive poly(l-glutamic acid) (PGA), flanked by two hydrophobic poly(l-alanine) blocks (PAla) (PAla5-PGA11-PAla5). This system showed a pH-responsive transition from short tapes to spherical aggregates by increasing the pH, as a result of deprotonation of the PGA block and a conformational change from α-helix to random coil. Increasing the ionic strength to physiological conditions (0.15 M) has triggered fibrillar self-assembly through intermolecular hydrogen bonding of PAla end-blocks that form ß-sheet nanostructures, in conjunction with charge screening of the central random coil PGA segments. At elevated concentrations a thermo-responsive free supporting hydrogel was obtained, consisting of rigid ß-sheet based twisted superfibers, resulting from hierarchical self-assembly of the copolypeptide. Yet, morphological transformation of this nanostructure was observed upon switching the pH from physiological conditions to pH 4. An unexpected morphology constituted of α-helix-based giant nanobelts was observed as a consequence of the secondary peptide transitions.
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Péptidos/química , Alanina/química , Ácido Glutámico/química , Hidrogeles/química , Concentración de Iones de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Concentración Osmolar , Estructura Secundaria de ProteínaRESUMEN
It is known that sensory deprivation, including postnatal whisker trimming, can lead to severe deficits in the firing rate properties of cortical neurons. Recent results indicate that development of synchronous discharge among cortical neurons is also activity influenced, and that correlated discharge is significantly impaired following loss of bilateral sensory input in rats. Here we investigate whether unilateral whisker trimming (unilateral deprivation or UD) after birth interferes in the same way with the development of synchronous discharge in cortex. We measured the coincidence of spikes among pairs of neurons recorded under urethane anesthesia in one whisker barrel field deprived by trimming all contralateral whiskers for 60 days after birth (UD), and in untrimmed controls (CON). In the septal columns around barrels, UD significantly increased the coincident discharge among cortical neurons compared with CON, most notably in layers II/III. In contrast, synchronous discharge was normal between layer IV UD barrel neurons: i.e., not different from CON. Thus, while bilateral whisker deprivation (BD) produced a global deficit in the development of synchrony in layer IV, UD did not block the development of synchrony between neurons in layer IV barrels and increased synchrony within septal circuits. We conclude that changes in synchronous discharge after UD are unexpectedly different from those recorded after BD, and we speculate that this effect may be due to the driven activity from active commissural inputs arising from the contralateral hemisphere that received normal activity levels during postnatal development.
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Neuronas/fisiología , Privación Sensorial/fisiología , Corteza Somatosensorial/fisiología , Percepción del Tacto/fisiología , Tacto/fisiología , Animales , Animales Recién Nacidos , Femenino , Masculino , Estimulación Física , Ratas , Ratas Long-Evans , Corteza Somatosensorial/crecimiento & desarrollo , Vibrisas/fisiologíaRESUMEN
An investigation of the constitutional adaptive gelation process of chitosan/cinnamaldehyde (C/Cy) dynagels is reported. These gels generate timely variant macroscopic organization across extended scales. In the first stage, imine-bond formation takes place "in-water" and generates low-ordered hydrogels. The progressive formation of imine bonds further induces "out-of-water" increased reactivity within interdigitated hydrophobic self-assembled layers of Cy, with a protecting environmental effect against hydrolysis and that leads to the stabilization of the imine bonds. The hydrophobic swelling due to Cy layers at the interfaces reaches a critical step when lamellar self-organized hybrids are generated (24â hours). This induces an important restructuration of the hydrogels on the micrometric scale, thus resulting in the formation of highly ordered microporous xerogel morphologies of high potential interest for chemical separations, drug delivery, and sensors.
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As selenium is an important part of the antioxidant enzymes and also because there are several studies suggesting a possible link between cancer and selenium deficiency, this paper presents a spectrophotometric method for the assay of Se(IV), using N,N-diethyl-p-phenylenediamine monohydrochloride as reagent. The proposed method is based on the reaction between the selenium and potassium iodide in low acidic medium, when iodine is released. This last product will further oxidise the new reagent. The final obtained product is strongly coloured in red and has an absorption maximum at 552 nm and molar extinction coefficient (ε) of 6.1 × 10(4) L mol(-1) cm(-1). The optimum working conditions were established, and the developed method was validated, being characterised by a good linearity (in the range of 0.5-3.0 µg/mL), a limit of detection (0.0573 µg/mL) and a limit of quantification (0.1737 µg/mL). At the same time, the repeatability, the precision of the method and the accuracy were established. The proposed and validated method was applied with good results for the determination of Se(IV) in spring and bottled water from Iasi and also in pharmaceutical and cosmetic products.
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Selenio/análisis , Oligoelementos/análisis , Monitoreo del Ambiente , Concentración de Iones de Hidrógeno , Yoduros/análisis , Yodo/análisis , Límite de Detección , Fenilendiaminas , Espectrofotometría/métodosRESUMEN
Cobalt(II) chloride (CoCl2) being in the vicinity of polyimide chains entails modifications in terms of the molecular dynamics, which are mainly governed by the possible presence of amic acid residual groups, by the transition-metal-type characteristics of cobalt and by the CoCl2 content. Polyimide was synthesized using poly(amic acid) according to the reaction of 2,2'-bis(3,4-dicarboxylphenyl)hexafluoropropane dianhydride (6FDA) with 3,3'-dimethyl-4,4'-diaminodiphenylmethane (MMDA) in N,N-dimethylacetamide. CoCl2 was added before the thermal imidization of the poly(amic acid). An experimental approach was designed to establish the interaction between the polyimide and CoCl2 and whether the interaction depends on the quantity of the salt. Evidence for the existence of residual amic acid groups was obtained using second derivative Fourier Transform Infrared Spectroscopy (FTIR) and with the help of 2D correlation spectroscopy (2D-COS). Moreover, FTIR, along with X-ray photoelectron spectroscopy (XPS), revealed the interaction between the polymer and CoCl2, primarily in the form of Co(II)-N coordinated bonds. Nevertheless, the coordination of cobalt with suitable atoms from the amic acid groups is not precluded. The results of dynamic mechanical analysis (DMA) featured a specific relaxation assigned to the presence of CoCl2 in the polymeric film and demonstrated that its (non)reinforcing effect depends on its content in the polyimide.
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We investigated the mineral concentrations of 61 honey samples from eight Romanian regions, employing advanced techniques to assess 30 chemical elements. Potassium emerged as the dominant element, showcasing significant variations across geographical locations. Essential minerals like calcium, magnesium, sodium, and manganese maintained consistent levels, while zinc, copper, and chromium were present in smaller proportions. Critically, lead and cadmium levels exceeded established safety limits in some samples, suggesting potential environmental contamination. Additionally, elevated levels of lithium, strontium, nickel, and aluminum were detected, hinting at possible atmospheric pollution. These findings highlight the importance of regional analysis, as mineral content varied significantly between locations. Furthermore, correlation analysis revealed interdependencies among elements, suggesting shared environmental influences. Advanced statistical techniques like hierarchical clustering and principal component analysis effectively captured the impact of geographical origin on honey composition. These insights contribute valuable information for future efforts in honey quality control, traceability systems, and regulatory measures. By providing valuable insights into environmental influences on honey composition, this study informs future research endeavors and paves the way for the development of robust regulatory measures to ensure honey safety for consumers.
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In various drug delivery systems, solid lipid nanoparticles are dominantly lipid-based nanocarriers. Amiodarone hydrochloride is an antiarrhythmic agent used to treat severe rhythm disturbances. It has variable and hard-to-predict absorption in the gastrointestinal tract because of its low solubility and high permeability. The aims of this study were to improve its solubility by encapsulating amiodarone into solid lipid nanoparticles using two excipients-Compritol® 888 ATO (pellets) (C888) as a lipid matrix and Transcutol® (T) as a surfactant. Six types of amiodarone-loaded solid lipid nanoparticles (AMD-SLNs) were obtained using a hot homogenization technique followed by ultrasonication with varying sonication parameters. AMD-SLNs were characterized by their size distribution, polydispersity index, zeta potential, entrapment efficiency, and drug loading. Based on the initial evaluation of the entrapment efficiency, only three solid lipid nanoparticle formulations (P1, P3, and P5) were further tested. They were evaluated through scanning electron microscopy, Fourier-transform infrared spectrometry, near-infrared spectrometry, thermogravimetry, differential scanning calorimetry, and in vitro dissolution tests. The P5 formulation showed optimum pharmaco-technical properties, and it had the greatest potential to be used in oral pharmaceutical products for the controlled delivery of amiodarone.
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Since medicinal plants are widely used in treating various diseases, phytoconstituents enrichment strategies are of high interest for plant growers. First of all, we investigated the impact of phytosociological cultivation on polyphenolic content (total flavonoids-TFL, and total polyphenols-TPC) of peppermint (Mentha piperita L.) and lemon balm (Melissa officinalis L.) leaves, using spectrophotometric methods. Secondly, the influence of chemical (NPK) and organic (BIO) fertilization on polyphenolic content and plant material quality was also assessed. Dry extracts were obtained from harvested leaves using hydroethanolic extraction solvents for further qualitative and quantitative assessment of phytoconstituents by FT-ICR MS and UHPLC-MS. Furthermore, the antioxidant activity of leaf extracts was determined in vitro using DPPH, ABTS and FRAP methods. Molecular docking simulations were employed to further evaluate the antioxidant potential of obtained extracts, predicting the interactions of identified phytochemicals with sirtuins. The concentration of polyphenols was higher in the plant material harvested from the phytosociological culture. Moreover, the use of BIO fertilizer led to the biosynthesis of a higher content of polyphenols. Higher amounts of phytochemicals, such as caffeic acid, were determined in extracts obtained from phytosociological crops. The antioxidant activity was dependent on polyphenols concentration, more potent inhibition values being observed for the extracts obtained from the phytosociological batches. Molecular docking studies and MM/PBSA calculations revealed that the obtained extracts have the potential to directly activate sirtuins 1, 5 and 6 through several polyphenolic compounds, such as rosmarinic acid, thus complementing the free radical scavenging activity with the potential stimulation of endogenous antioxidant defense mechanisms. In conclusion, growing medicinal plants in phytosociological cultures treated with biofertilizers can have a positive impact on plant material quality, concentration in active constituents and biological activity.
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Oxidative stress is among the major triggers for many important human functional disorders, which often lead to various metabolic or tissue diseases. The aim of the study is to obtain five standardized vegetal extracts (Cynarae extractum-CE, Rosmarini extractum-RE, Taraxaci extractum-TE, Cichorii extractum-CHE, and Agrimoniae extractum-AE) that contain active principles with an essential role in protecting liver cells against free radicals and quantify their antioxidant actions. The compounds of therapeutic interest from the analyzed extracts were identified and quantified using the UHPLC-HRMS/MS technique. Thus, the resulting identified compounds were 28 compounds in CE, 48 compounds in RE, 39 compounds in TE, 43 compounds in CHE, and 31 compounds in AE. These compounds belong to the class of flavonoids, isoflavones, phenolic acids and dicarboxylic acids, depsides, diterpenes, triterpenes, sesquiterpenes, proanthocyanidins, or coumarin derivatives. From the major polyphenolic compounds quantified in all the extracts analyzed by UHPLC-HRMS/MS, considerable amounts have been found for chlorogenic acid (619.8 µg/g extract for TE-2032.4 µg/g extract for AE), rutoside (105.1 µg/g extract for RE-1724.7 µg/g extract for AE), kaempferol (243 µg/g extract for CHE-2028.4 µg/g extract for CE), and for naringenin (383 µg/g extract for CHE-1375.8 µg/g extract for AE). The quantitative chemical analysis showed the highest content of total phenolic acids for AE (24.1528 ± 1.1936 g chlorogenic acid/100 g dry extract), the highest concentration of flavones for RE (6.0847 ± 0.3025 g rutoside/100 g dry extract), and the richest extract in total polyphenols with 31.7017 ± 1.2211 g tannic acid equivalent/100 g dry extract for AE. Several methods (DPPH, ABTS, and FRAP) have been used to determine the in vitro total antioxidant activity of the extracts to evaluate their free radical scavenging ability, influenced by the identified compounds. As a result, the correlation between the content of the polyphenolic compounds and the antioxidant effect of the extracts has been demonstrated. Statistically significant differences were found when comparing the antiradical capacity within the study groups. Although all the analyzed extracts showed good IC50 values, which may explain their antihepatotoxic effects, the highest antioxidant activity was obtained for Agrimoniae extractum (IC50ABTS = 0.0147 mg/mL) and the lowest antioxidant activity was obtained for Cynarae extractum (IC50ABTS = 0.1588 mg/mL). Furthermore, the hepatoprotective potential was evaluated in silico by predicting the interactions between the determined phytochemicals and key molecular targets relevant to liver disease pathophysiology. Finally, the evaluation of the pharmacognostic and phytochemical properties of the studied extracts validates their use as adjuvants in phytotherapy, as they reduce oxidative stress and toxin accumulation and thus exert a hepatoprotective effect at the cellular level.
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A novel liposome/hydrogel soft nanocomposite was explored as a controlled drug delivery system. A P2VP-PAA-PnBMA biocompatible, pH-responsive triblock terpolymer was used as an injectable gelator, entrapping PC/Chol liposomes loaded with calcein as hydrophilic model drug. The composite hydrogel was formed in vitro through a pH-induced sol-gel transition by dialysis against buffer under physiological conditions and at polymer concentration as low as 1 wt %. Excellent control of the calcein release was achieved just by adjusting the gelator concentration; that is, from 1 to 1.5 wt %, the drug release period was significantly prolonged from 14 to 32 days.
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Hidrogeles , Concentración de Iones de Hidrógeno , Liposomas , Nanocompuestos , Preparaciones Farmacéuticas/administración & dosificación , Línea Celular , Humanos , Microscopía Confocal , Microscopía Electrónica de Transmisión , Modelos QuímicosRESUMEN
The sex-bias of disease susceptibility has remained a puzzling aspect of several autoimmune conditions, including post-infection viral autoimmunity. In the last half of the twentieth century, the incidence rate of female-biased autoimmunity has steadily increased independent of medical advances. This has suggested a role for environmental factors, such as endocrine disrupting chemicals, which have been described to interfere with endocrine signaling. Endocrine involvement in the proper function of innate and adaptive immunity has also been defined, however, these two areas have rarely been reviewed in correlation. In addition, studies addressing the effects of endocrine disruptors have reported findings resulting from a broad range of exposure doses, schedules and models. This experimental heterogeneity adds confusion and may mislead the translation of findings to human health. Our work will normalize results across experiments and provide a necessary summary relevant to human exposure. Through a novel approach, we describe how different categories of ubiquitously used environmental endocrine disruptors interfere with immune relevant endocrine signaling and contribute to autoimmunity. We hope this review will guide identification of mechanisms and concentration-dependent EDC effects important not only for the sex-bias of autoimmunity, but also for other conditions of immune dysfunction, including post-infection autoreactivity such as may arise following severe acute respiratory syndrome coronavirus 2, Epstein-Barr virus, Herpes Simplex virus.
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The health crisis generated by the COVID-19 pandemic has induced, among other things, an increase in the importance of remote work or teleworking (TL) in the current period. The objective of this research is to identify the economic and social impact of telework in changing the behavior of employees in Romania. The research was conducted approximately one year after the onset of the pandemic until the beginning of the vaccination period in Romania. The research proposed includes three main directions of analysis of the extracted data, which are related to telework efficiency, this being considered one of the most important indicators for a company. In order to obtain conclusive results, we used a mixed methodology, combining results obtained through a survey based on a self-administered electronic questionnaire, with a data mining analysis. Detailed analysis of the groups identified based on work efficiency allowed us to highlight the most common employee profiles. This analysis was doubled by a second classification experiment, which provided us a more detailed analysis of the groups identified based on job satisfaction and highlighted the most common employee profiles. The expansion of telework in various economic areas is a result of adaptation to the new economic and social conditions caused by the COVID-19 pandemic.
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COVID-19 , Minería de Datos , Humanos , Pandemias , SARS-CoV-2 , Cambio Social , TeletrabajoRESUMEN
Several theories have proposed a functional role for synchronous neuronal firing in generating the neural code of a sensory perception. Synchronous neural activity develops during a critical postnatal period of cortical maturation, and severely reducing neural activity in a sensory pathway during this period could interfere with the development of coincident discharge among cortical neurons. Loss of such synchrony could provide a fundamental mechanism for the degradation of acuity shown in behavioral studies. We tested the hypothesis that synchronous discharge of barrel cortex neurons would fail to develop after sensory deprivation produced by bilateral whisker trimming from birth to postnatal day 60. By studying the correlated discharge of cortical neuron pairs, we found evidence for strong correlated firing in control animals, and this synchrony was almost absent among pairs of cortical barrel neurons in deprived animals. The degree of synchrony impairment was different in subregions of rat barrel cortex. The model that best fits the data is that cortical neurons receiving direct inputs from the primary sensory (lemniscal) pathway show the greatest decrement in synchrony following sensory deprivation, while neurons with diverse inputs from other areas of thalamus and cortex are relatively less affected in this dimension of cortical function.