Overexpression of human epidermal growth factor receptor-2 (HER-2) occurs in 20% of all breast cancer subtypes, especially those that present the worst prognostic outcome through a very invasive and ...aggressive tumour. HCC-1954 (HER-2+) is a highly invasive, metastatic cell line, whereas MCF-7 is mildly aggressive and non-invasive. We investigated membrane proteins from both cell lines that could have a pivotal biological significance in metastasis. Membrane protein enrichment for HCC-1954 and MCF-7 proteomic analysis was performed. The samples were analysed and quantified by mass spectrometry. High abundance membrane proteins were confirmed by Western blot, immunofluorescence, and flow cytometry. Protein interaction prediction and correlations with the Cancer Genome Atlas (TCGA) patient data were conducted by bioinformatic analysis. In addition, β1 integrin expression was analysed by Western blot in cells upon trastuzumab treatment. The comparison between HCC-1954 and MCF-7 membrane-enriched proteins revealed that proteins involved in cytoskeleton organisation, such as HER-2, αv and β1 integrins, E-cadherin, and CD166 were more abundant in HCC-1954. β1 integrin membrane expression was higher in the HCC-1954 cell line resistant after trastuzumab treatment. TCGA data analysis showed a trend toward a positive correlation between HER-2 and β1 integrin in HER-2+ breast cancer patients. Differences in protein profile and abundance reflected distinctive capabilities for aggressiveness and invasiveness between HCC-1954 and MCF-7 cell line phenotypes. The higher membrane β1 integrin expression after trastuzumab treatment in the HCC-1954 cell line emphasised the need for investigating the contribution of β1 integrin modulation and its effect on the mechanism of trastuzumab resistance.
Brazilian pine-fruit shells (Araucaria angustifolia) in natural form and as activated carbon were tested as adsorbents for the removal of remazol black B (RB) textile dye from aqueous effluents. The ...effects of shaking time, adsorbent dosage and pH on the adsorption capacity were studied. RB uptake was favorable at pH values ranging from 2.0 to 2.5 and from 2.0 to 7.0 for the biosorbent and the activated carbon, respectively. The contact time required to obtain the equilibrium using the biosorbent and the activated carbon was 12 and 4h at 298K, respectively. The fractionary-order kinetic model provided the best fit to experimental data compared with other models. Equilibrium data were better fit to the Sips isotherm model using the biosorbent as well as the activated carbon. The enthalpy and entropy of adsorption of RB were obtained from adsorption experiments ranging from 298 to 323K. Simulated dyehouse effluents were used to check the applicability of the proposed adsorbents for effluent treatment.
► The PW and AC-PW are good adsorbents to remove RB dye from aqueous solutions. ► AC-PW is an activated carbon prepared from the Brazilian-pine fruit shell. ► PW is the unmodiffied Brazillian pine fruit shell. ► PW maximum sorption capacity was 74.6 mg g–1. ► AC-PW maximum sorption capacity was 446.2 mg g–1. ► AC-PW adsorbent removed 94% of the mixture of dyes in a synthetic dye effluent.
Background
Effective and safe vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are critical to controlling the COVID-19 pandemic and will remain the most important tool ...in limiting the spread of the virus long after the pandemic is over.
Methods
We bring pioneering contributions on the maintenance of the immune response over a year on a real-life basis study in 1,587 individuals (18-90 yrs, median 39 yrs; 1,208 female/379 male) who underwent vaccination with two doses of CoronaVac and BNT162b2 booster after 6-months of primary protocol.
Findings
Elevated levels of anti-spike IgG antibodies were detected after CoronaVac vaccination, which significantly decreased after 80 days and remained stable until the introduction of the booster dose. Heterologous booster restored antibody titers up to-1·7-fold, changing overall seropositivity to 96%. Titers of neutralising antibodies to the Omicron variant were lower in all timepoints than those against Delta variant. Individuals presenting neutralising antibodies against Omicron also presented the highest titers against Delta and anti-Spike IgG. Cellular immune response measurement pointed out a mixed immune profile with a robust release of chemokines, cytokines, and growth factors on the first month after CoronaVac vaccination followed by a gradual reduction over time and no increase after the booster dose. A stronger interaction between those mediators was noted over time. Prior exposure to the virus leaded to a more robust cellular immune response and a rise in antibody levels 60 days post CoronaVac than in individuals with no previous COVID-19. Both vaccines were safe and well tolerated among individuals.
Interpretation
Our data approach the effectiveness of CoronaVac association with BNT162b2 from the clinical and biological perspectives, aspects that have important implications for informing decisions about vaccine boosters.
Funding
Fiocruz, Brazil.
The non-classical histocompatibility antigen G (HLA-G) is an immune checkpoint molecule that has been implicated in viral disorders. We evaluated the plasma soluble HLA-G (sHLA-G) in 239 individuals, ...arranged in COVID-19 patients (n = 189) followed up at home or in a hospital, and in healthy controls (n = 50). Increased levels of sHLA-G were observed in COVID-19 patients irrespective of the facility care, gender, age, and the presence of comorbidities. Compared with controls, the sHLA-G levels increased as far as disease severity progressed; however, the levels decreased in critically ill patients, suggesting an immune exhaustion phenomenon. Notably, sHLA-G exhibited a positive correlation with other mediators currently observed in the acute phase of the disease, including IL-6, IL-8 and IL-10. Although sHLA-G levels may be associated with an acute biomarker of COVID-19, the increased levels alone were not associated with disease severity or mortality due to COVID-19. Whether the SARS-CoV-2 per se or the innate/adaptive immune response against the virus is responsible for the increased levels of sHLA-G are questions that need to be further addressed.
Cosmetics composed of synthetic and/or semi-synthetic polymers, associated or not with natural polymers, exhibit a dashing design, with thermal and chemo-sensitive properties. Cosmetic polymers are ...also used for the preparation of nanoparticles for the delivery of, e.g., fragrances, with the purpose to modify their release profile and also reducing the risk of evaporation. Besides, other cosmetically active nutrients, dermal permeation enhancers, have also been loaded into nanoparticles to improve their bioactivities on the skin. The use of natural polymers in cosmetic formulations is of particular relevance because of their biocompatible, safe, and eco-friendly character. These formulations are highly attractive and marketable to consumers, and are suitable for a plethora of applications, including make-up, skin, and hair care, and as modifiers and stabilizers. In this review, natural synthetic, semi-synthetic, and synthetic polymers are discussed considering their properties for cosmetic applications. Their uses in conventional and novel formulations are also presented.
Using sulfated polysaccharides (SP) in fish sperm freezing medium promotes cell maintenance.
To evaluate the effect of different SP concentrations, extracted from two seaweeds (Gracilaria domingensis ...and Ulva fasciata), as a supplement to the sperm freezing medium of Prochilodus brevis.
Five semen pools were diluted in a solution composed of 5% glucose, 10 % dimethyl sulfoxide (DMSO) and different SP concentrations (0, 0.5, 1.0, 1.5, 2.0, 2.5 or 3.0 mg/mL). The samples were cryopreserved and, after 7 days, rewarmed and analyzed for morphology, plasma membrane integrity, DNA integrity, mitochondrial activity and sperm kinetics total motility, progressive motility, curvilinear velocity (VCL), straight line velocity (VSL), average path velocity (VAP), linearity (LIN), and wobble (WOB).
There was no interaction between seaweed and SP concentrations. Similar effects were observed with SP extracted from the two seaweeds, regardless of concentration. When comparing the SP concentrations, regardless of the seaweed, 1.0 mg/mL SP showed better results for VCL and VSL. For VAP and WOB, 1.0 mg/mL SP showed better results, but differed from 3.0 mg/mL. LIN followed the same pattern, but differed from SP at 2.5 and 3.0 mg/mL. For progressive motility, 1.0 mg/mL G. domingensis showed superior results compared to the control. For mitochondrial activity, G. domingensis was superior to U. fasciata, regardless of concentration. The lowest concentrations (0.5 and 1.0 mg/mL) showed the best results, regardless of the seaweed. However, the control was superior to all treatments tested.
G. domingensis SP at the lowest concentrations might be a potential supplement to the P. brevis freezing medium. doi.org/10.54680/fr22210110412.
Margarines and spreads contribute greatly to the intake of saturated and trans fats in the diet. Therefore, the objective of this work was to produce margarines using the oleogel technology and to ...verify the physical, thermal, oxidative, and sensorial properties of this product during six months of shelf life, comparing it with commercial margarine. When compared with commercial margarine, the oleogel margarine showed similar color results. Due to the different structural shape, the results of microstructure and the melting curve were differentiated, but this indicated a structure more resistant to temperature oscillations and an overall softer product. However, the sensorial difference between the samples was easily detected by the consumers, mainly with respect to the parameters of taste, texture, and overall impression. It was concluded that it is possible to produce margarines using the oleogel technology, which display good physical properties, similar shelf life, and improved nutritional characteristics.
Although photodynamic therapy (PDT) of cancer has been continuously improved, its efficiency is still limited by the high toxicity in the absence of irradiation, aggregation and deactivation by ...biomolecules of the most common photosensitizers (PS). The association of PS to nanoparticles (NPs) can be a promising tool to overcome these limitations and also to enhance PS tumoral selectivity. In addition, the association of PS to metallic NPs may provide the modulation of PS fluorescence and also the enhancement of PS photoactivity due to the electronic coupling with NPs plasmon effect. Adversely to the innumerous work on the coupling of PS to metallic NPs, the application of bimetallic NPs with this goal has not been explored yet. In this work we investigated the physicochemical properties and cytotoxicity of bimetallic gold-platinum NPs (AuPtNPs) conjugated to a chlorin molecule modified with a thiol group. Additionally, chlorin was coupled to AuNPs for comparative purposes since these have been the most commonly used NPs in PDT. The results showed that both platforms promoted the chlorin solubility in water which is crucial in biological applications. Despite the enhancement of photoactivity promoted by both NPs in comparison with chlorin in solution, chlorin-conjugated with AuPtNPs proved to be a more suitable platform for PDT application, since it showed a lower dark citotoxicity, as well as a higher generation of singlet oxygen and cell internalization compared with chlorin-conjugated AuNPs. It is important to highlight that this is the first work reporting on the enhancement of PS photoactivity by its conjugation to AuPtNPs.
Accurate testing to detect SARS-CoV-2 RNA is key to counteract the virus spread. Nonetheless, the number of diagnostic laboratories able to perform qPCR tests is limited, particularly in developing ...countries. We describe the use of a virus-inactivating, denaturing solution (DS) to decrease virus infectivity in clinical specimens without affecting RNA integrity. Swab samples were collected from infected patients and from laboratory personnel using a commercially available viral transport solution and the in-house DS. Samples were tested by RT-qPCR, and exposure to infective viruses was also accessed by ELISA. The DS used did not interfere with viral genome detection and was able to maintain RNA integrity for up to 16 days at room temperature. Furthermore, virus loaded onto DS were inactivated, as attested by attempts to grow SARS-CoV-2 in cell monolayers after DS desalt filtration to remove toxic residues. The DS described here provides a strategy to maintain diagnostic accuracy and protects diagnostic laboratory personnel from accidental infection, as it has helped to protect our lab crew.
Abstract
Lipid and cholinergic mediators are inflammatory regulators, but their role in the immunopathology of COVID-19 is still unclear. Here, we used human blood and tracheal aspirate (TA) to ...investigate whether acetylcholine (Ach), fatty acids (FAs), and their derived lipid mediators (LMs) are associated with COVID-19 severity. First, we analyzed the perturbation profile induced by SARS-CoV-2 infection in the transcriptional profile of genes related to the ACh and FA/LM pathways. Blood and TA were used for metabolomic and lipidomic analyses and for quantification of leukocytes, cytokines, and ACh. Differential expression and coexpression gene network data revealed a unique transcriptional profile associated with ACh and FA/LM production, release, and cellular signaling. Transcriptomic data were corroborated by laboratory findings: SARS-CoV-2 infection increased plasma and TA levels of arachidonic acid, 5-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid, 11-hydroxy-5Z,8Z,12E,14Z-eicosatetraenoic acid, and ACh. TA samples also exhibited high levels of PGE2, thromboxane B2, 12-oxo-5Z,8Z,10E,14Z-eicosatetraenoic acid, and 6-trans-leukotriene B4. Bioinformatics and experimental approaches demonstrated robust correlation between transcriptional profile in Ach and FA/LM pathways and parameters of severe COVID-19. As expected, the increased neutrophil-to-lymphocyte ratio, neutrophil counts, and cytokine levels (IL-6, IL-10, IL-1β, and IL-8) correlated with worse clinical scores. Glucocorticoids protected severe and critical patients and correlated with reduced Ach levels in plasma and TA samples. We demonstrated that pulmonary and systemic hyperinflammation in severe COVID-19 are associated with high levels of Ach and FA/LM. Glucocorticoids favored the survival of patients with severe/critical disease, and this effect was associated with a reduction in ACh levels.