HIV-Associated neurocognitive disorder (HAND) is one of the major concerns since it persists in 40% of this population. Nowadays, HAND neuropathogenesis is considered to be caused by the infected cells that cross the brain–blood barrier and produce viral proteins that can be secreted and internalized into neurons leading to disruption of cellular processes. The evidence points to viral proteins such as Tat as the causal agent for neuronal alteration and thus HAND. The hallmarks in Tat-induced neurodegeneration are endoplasmic reticulum stress and mitochondrial dysfunction. Sirtuins (SIRTs) are NAD+-dependent deacetylases involved in mitochondria biogenesis, unfolded protein response, and intrinsic apoptosis pathway. Tat interaction with these deacetylases causes inhibition of SIRT1 and SIRT3. Studies revealed that SIRTs activation promotes neuroprotection in neurodegenerative diseases such Alzheimer’s and Parkinson’s disease. Therefore, this review focuses on Tat-induced neurotoxicity mechanisms that involve SIRTs as key regulators and their modulation as a therapeutic strategy for tackling HAND and thereby improving the quality of life of people living with HIV. 相似文献
Mast cells (MCs) have relevant participation in inflammatory and vascular hyperpermeability events, responsible for the action of the kallikrein–kinin system (KKS), that affect patients inflicted by the severe form of COVID-19. Given a higher number of activated MCs present in COVID-19 patients and their association with vascular hyperpermeability events, we investigated the factors that lead to the activation and degranulation of these cells and their harmful effects on the alveolar septum environment provided by the action of its mediators. Therefore, the pyroptotic processes throughout caspase-1 (CASP-1) and alarmin interleukin-33 (IL-33) secretion were investigated, along with the immunoexpression of angiotensin-converting enzyme 2 (ACE2), bradykinin receptor B1 (B1R) and bradykinin receptor B2 (B2R) on post-mortem lung samples from 24 patients affected by COVID-19. The results were compared to 10 patients affected by H1N1pdm09 and 11 control patients. As a result of the inflammatory processes induced by SARS-CoV-2, the activation by immunoglobulin E (IgE) and degranulation of tryptase, as well as Toluidine Blue metachromatic (TB)-stained MCs of the interstitial and perivascular regions of the same groups were also counted. An increased immunoexpression of the tissue biomarkers CASP-1, IL-33, ACE2, B1R and B2R was observed in the alveolar septum of the COVID-19 patients, associated with a higher density of IgE+ MCs, tryptase+ MCs and TB-stained MCs, in addition to the presence of intra-alveolar edema. These findings suggest the direct correlation of MCs with vascular hyperpermeability, edema and diffuse alveolar damage (DAD) events that affect patients with a severe form of this disease. The role of KKS activation in events involving the exacerbated increase in vascular permeability and its direct link with the conditions that precede intra-alveolar edema, and the consequent DAD, is evidenced. Therapy with drugs that inhibit the activation/degranulation of MCs can prevent the worsening of the prognosis and provide a better outcome for the patient. 相似文献
Poly(ethylene terephthalate)-based molecularly imprinted polymers (MIPs) were synthesized, and their recognition capability was evaluated. Adsorption isotherm was described by the Langmuir model and the maximum adsorption capacity of MIPTy reached 172.4 mg g−1 in water at pH 6.2. A recognition coefficient of 1.17 was obtained. A solid-phase extraction cartridge was manufactured and its behavior was evaluated for tylosin extraction from aqueous and milk samples. An off-line SPE-UV method was applied. An acceptable linearity was obtained in the range of 1–20 μg ml−1 and the average recovery at three spike levels in milk samples was higher than 92%. The limit of quantification was 2.6 × 10−2 μg ml−1. The manufactured SPE cartridge has a great potential for clean-up processes in complex media. The cartridge offers a fast and sensitive option to the existing sorbents for extracting this drug from milk samples. 相似文献
This work shows the preparation of ethylene vinyl acetate copolymer/banana starch/Cloisite 20A organoclay (EVA/starch/C20A) nanocomposites by melt processing. Wide angle X-ray diffraction (WAXD), field emission scanning electron microscopy (FE-SEM), differential scanning calorimetry and thermogravimetric analysis were used to characterize the obtained nanocomposites. Mechanical properties were also determined. In addition, the performance of the nanocomposite films under composting was preliminarily studied; it was conducted using the soil burial test method. Despite knowing that the starch is difficult to process by extrusion, nanocomposite films with high homogeneity were obtained. In this case, C20A organoclay acts as an effective surfactant to make the starch natural polymer compatible with the EVA synthetic polymer. The good compatibility between EVA, starch and C20A clay was also deduced by the formation of intercalated and intercalated-exfoliated structures determined by WAXD and FE-SEM. Physical evidence of the damage in EVA/starch/C20A nanocomposite films after the composting test was observed. It is worth noting that despite the absence of starch, the EVA/C20A nanocomposite film, used as a control, also showed surface damage. This behavior is related to the organic modifier linked to clay C20A, which contains molecules derived from fatty acids that can be used as a food source for microorganisms.
Studies about kinetics and modeling of production parameters for biosurfactants are essential to the development of efficient processes from an economic point of view. In this sense, this work evaluated the performance of four nonstructured models to explain the experimental data for biomass growth, substrate consumption, and rhamnolipid production using glycerol as carbon source and a Pseudomonas aeruginosa strain. The kinetic parameters of each model were estimated using a global search method known as genetic algorithm and numerical discretization of differential equations by the Runge–Kutta 4th order method. The main result of this study showed that the Monod model best represented the experimental data, with μmax values of 0.06 h−1, KS of 50.8 g L−1, YX/S of 0.43 g g−1, and YP/X equal to 0.017 g g−1. 相似文献
Isolation and characterization of oligosaccharides from caseinomacropeptide (CMP) are important in understanding the biological and functional properties of CMP. However, it is difficult to achieve this goal, due to the high degree of isomerism present in these types of compounds. In this study, the sialylated oligosaccharides derived from ovine and caprine CMP were released as oligosaccharide alditols by reductive β-elimination and subsequently separated and characterized using graphite carbon column liquid chromatography–negative electrospray ionization ion trap tandem mass spectrometry (LC/ESI(?)-MSn). Although, the chromatographic resolution of isomeric oligosaccharides was not achieved perfectly, the characteristic tandem mass spectra of these compounds allowed differentiating and confirming unequivocally the structure of each one of the oligosaccharides. In CMP of both species, four trisaccharides and four tetrasaccharides were identified as O-glycans. Their chemical structures were identified to be Galβ1-3(NeuAcα2-6)GalNAcol, NeuAcα2-3Galβ1-3GalNAcol, Galβ1-3(NeuGcα2-6)GalNAcol, NeuGcα2-3Galβ1-3GalNAcol, NeuAcα2-3Galβ1-3(NeuGcα2-6)GalNAcol, NeuGcα2-3Galβ1-3(NeuAcα2-6)GalNAcol, NeuAcα2-3Galβ1-3(NeuAcα2-6)GalNAcol, and NeuGcα2-3Galβ1-3(NeuGcα2-6)GalNAcol. The LC/MSn methodology using an ion trap-type mass analyzer shown in this study is of general applicability for determination of short O-glycan oligosaccharides. 相似文献
Theophylline (3-methyxanthine) is a historically prominent drug used to treat respiratory diseases, alone or in combination with other drugs. The rapid onset of the COVID-19 pandemic urged the development of effective pharmacological treatments to directly attack the development of new variants of the SARS-CoV-2 virus and possess a therapeutical battery of compounds that could improve the current management of the disease worldwide. In this context, theophylline, through bronchodilatory, immunomodulatory, and potentially antiviral mechanisms, is an interesting proposal as an adjuvant in the treatment of COVID-19 patients. Nevertheless, it is essential to understand how this compound could behave against such a disease, not only at a pharmacodynamic but also at a pharmacokinetic level. In this sense, the quickest approach in drug discovery is through different computational methods, either from network pharmacology or from quantitative systems pharmacology approaches. In the present review, we explore the possibility of using theophylline in the treatment of COVID-19 patients since it seems to be a relevant candidate by aiming at several immunological targets involved in the pathophysiology of the disease. Theophylline down-regulates the inflammatory processes activated by SARS-CoV-2 through various mechanisms, and herein, they are discussed by reviewing computational simulation studies and their different applications and effects. 相似文献