Electrospray ionization mass spectrometry fingerprinting of Brazilian cacha?as produced in copper alembic and in stainless-steel column stills

Brazilian cacha?a can be produced in two different ways: distilled in stainless steel column or in copper alembic stills. We evaluated 36 samples of commercial non-aged cacha?as: 18 samples of sweetened cacha?as distilled in stainless steel column, and 18 samples distilled in copper alembic stills. Fingerprints were obtained through electrospray ionization mass spectrometry by recording the intensity of the 15 most abundant ions. Principal component analysis was applied to the data and separated the samples in two groups. However, after sample standardization with sugar (20?g?L^?1), it was not possible to group them by type of distillation. The results showed that the technique applied did not allow differentiation of cacha?as based on the distillation system, but for the presence or absence of sugar in them.     

Neuroprotective Role of Liver Growth Factor “LGF” in an Experimental Model of Cerebellar Ataxia

Cerebellar ataxias (CA) comprise a heterogeneous group of neurodegenerative diseases characterized by a lack of motor coordination. They are caused by disturbances in the cerebellum and its associated circuitries, so the major therapeutic goal is to correct cerebellar dysfunction. Neurotrophic factors enhance the survival and differentiation of selected types of neurons. Liver growth factor (LGF) is a hepatic mitogen that shows biological activity in neuroregenerative therapies. We investigate the potential therapeutic activity of LGF in the 3-acetylpiridine (3-AP) rat model of CA. This model of CA consists in the lesion of the inferior olive-induced by 3-AP (40 mg/kg). Ataxic rats were treated with 5 µg/rat LGF or vehicle during 3 weeks, analyzing: (a) motor coordination by using the rota-rod test; and (b) the immunohistochemical and biochemical evolution of several parameters related with the olivo-cerebellar function. Motor coordination improved in 3-AP-lesioned rats that received LGF treatment. LGF up-regulated NeuN and Bcl-2 protein levels in the brainstem, and increased calbindin expression and the number of neurons receiving calbindin-positive projections in the cerebellum. LGF also reduced extracellular glutamate and GABA concentrations and microglia activation in the cerebellum. In view of these results, we propose LGF as a potential therapeutic agent in cerebellar ataxias.     

New functional fibre in milk puddings: Effect on sensory properties and consumers' acceptability

The effect of the addition of a new functional fibre (high-amylose maize starch, HAMS, as a source of resistant starch), recently available in the market, on sensory characteristics and consumers' acceptability of milk puddings was studied. Milk puddings containing modified waxy maize starch and κ-carrageenan were produced with different HAMS concentrations (0, 1, 2, 3 and 4%). Higher HAMS concentration caused changes in the sensory characteristics of milk puddings. Particularly, sensory attributes such as some roughness, rough afterfeel and floury taste appeared. Besides, the addition of HAMS caused an increase in manual and oral thickness and a decrease in creaminess, melting, and sweetness. A HAMS enrichment level of 1.4% in this product was estimated as the maximum concentration that does not significantly modify consumers' overall acceptability. Using survival analysis the proportion of consumers who would buy milk desserts containing 1.4 % HAMS was estimated as 71%. Consumers more interested in consuming functional foods enriched with fibre were more tolerant to the sensory changes caused by the addition of HAMS to the milk puddings.     

SEM and AFM characterization of surface of two RMGICs for degradation before and after modification with bioactive glass ceramic

Objectives: The aim of this study was to evaluate the effect of bioactive glass–ceramic particles (Biosilicate®) addition on surface nanoroughness and topography of Resin-modified glass ionomer cements (RMGICs).

Methods: Experimental materials were made by incorporating 2 wt% of Biosilicate® into Fuji II LC® (FL) and Vitremer® (VT) powders. Disks of RMGICs (with and without Biosilicate®) measuring 0.5 cm (diameter) × 0.5 mm (thickness) were fabricated and polished. Samples were stored at 37 °C in dry or immersed in distilled water for 30 days. Digital images (20 × 20 μm) from the surfaces were obtained by means of an atomic force microscopy. Three images were acquired for each sample, and four nanoroughness measurements were performed in each image. Nanoroughness (Ra, nm) was assessed by Nanoscope Software V7. Data were analyzed with ANOVA and Student–Newman–Keuls multiple comparisons (p < 0.05). SEM images were obtained for surface topography analysis.

Results: FL was significantly rougher than VT (p < 0.05) in wet and dry conditions. The addition of Biosilicate® increased the surface roughness in VT and decreased in FL, regardless of the storage media (p ≤ 0.05). No differences existed between materials and storage conditions after Biosilicate® addition. Significance: The Biosilicate® particles addition produced changes on the surface nanoroughness of the RMGICs. These changes depended on the particles size of the original cements in dry conditions. In water storage, dissolution of the Biosilicate® particles, a silica-rich gel formation, and a hydroxyl carbonate apatite precipitation on the surface of the materials changed the nanoroughness surface. FL was the roughest in both conditions.

Significance: The Biosilicate® particles addition produced changes on the surface nanoroughness of the RMGICs. These changes depended on the particles size of the original cements in dry conditions. In water storage, dissolution of the Biosilicate® particles, a silica-rich gel formation, and a hydroxyl carbonate apatite precipitation on the surface of the materials changed the nanoroughness surface. FL was the roughest in both conditions.     

N‐Benzyl‐4‐((heteroaryl)methyl)benzamides: A New Class of Direct NADH‐Dependent 2‐trans Enoyl–Acyl Carrier Protein Reductase (InhA) Inhibitors with Antitubercular Activity

Isoniazid (INH) remains one of the cornerstones of antitubercular chemotherapy for drug‐sensitive strains of M. tuberculosis bacteria. However, the increasing prevalence of multidrug‐resistant (MDR) and extensively drug‐resistant (XDR) strains containing mutations in the KatG enzyme, which is responsible for the activation of INH into its antitubercular form, have rendered this drug of little or no use in many cases of drug‐resistant tuberculosis. Presented herein is a novel family of antitubercular direct NADH‐dependent 2‐trans enoyl–acyl carrier protein reductase (InhA) inhibitors based on an N‐benzyl‐4‐((heteroaryl)methyl)benzamide template; unlike INH, these do not require prior activation by KatG. Given their direct InhA target engagement, these compounds should be able to circumvent KatG‐related resistance in the clinic. The lead molecules were shown to be potent inhibitors of InhA and showed activity against M. tuberculosis bacteria. This new family of inhibitors was found to be chemically tractable, as exemplified by the facile synthesis of analogues and the establishment of structure–activity relationships. Furthermore, a co‐crystal structure of the initial hit with the enzyme is disclosed, providing valuable information toward the design of new InhA inhibitors for the treatment of MDR/XDR tuberculosis.     

Polymeric Nanoparticle-Based Photodynamic Therapy for Chronic Periodontitis in Vivo

Antimicrobial photodynamic therapy (aPDT) is increasingly being explored for treatment of periodontitis. Here, we investigated the effect of aPDT on human dental plaque bacteria in suspensions and biofilms in vitro using methylene blue (MB)-loaded poly(lactic-co-glycolic) (PLGA) nanoparticles (MB-NP) and red light at 660 nm. The effect of MB-NP-based aPDT was also evaluated in a clinical pilot study with 10 adult human subjects with chronic periodontitis. Dental plaque samples from human subjects were exposed to aPDT—in planktonic and biofilm phases—with MB or MB-NP (25 µg/mL) at 20 J/cm² in vitro. Patients were treated either with ultrasonic scaling and scaling and root planing (US + SRP) or ultrasonic scaling + SRP + aPDT with MB-NP (25 µg/mL and 20 J/cm²) in a split-mouth design. In biofilms, MB-NP eliminated approximately 25% more bacteria than free MB. The clinical study demonstrated the safety of aPDT. Both groups showed similar improvements of clinical parameters one month following treatments. However, at three months ultrasonic SRP + aPDT showed a greater effect (28.82%) on gingival bleeding index (GBI) compared to ultrasonic SRP. The utilization of PLGA nanoparticles encapsulated with MB may be a promising adjunct in antimicrobial periodontal treatment.     

Doxycycline Decreases Atherosclerotic Lesions in the Aorta of ApoE-⁄- and Ovariectomized Mice with Correlation to Reduced MMP-2 Activity

Atherogenic events promote changes in vessel walls, with alteration of the redox state, and increased activity of matrix metalloproteinases (MMPs). Thus, this study aims to evaluate aortic remodeling, MMP activity, and reactive oxygen species (ROS) levels after treatment with doxycycline in ApoE^-⁄- and ovariectomized mice (OVX). Female ApoE^-⁄--knockout mice (5 weeks) were submitted to ovariectomy surgery to induce experimental menopause. They then received chow enriched with 1% cholesterol to induce hypercholesterolemia. The animals were divided into two experimental groups: ApoE^-⁄-/OVX vehicle and ApoE^-⁄-/OVX doxycycline (30 mg/kg) administered by gavage once a day for 28 days (15th to the 18th week of life). Blood samples were collected to measure total cholesterol and fractions. The aorta was used for morphometry and to measure the activity and expression of MMP-2 and ROS levels. The ApoE^-⁄-/OVX doxycycline group showed no change in total and fraction cholesterol levels. However, there was a reduction in ROS levels, MMP-2 expression, and activity that correlated with a decrease in atherosclerotic lesions relative to the ApoE^-⁄-/OVX vehicle (p > 0.05). Therefore, we conclude that doxycycline in ApoE^-⁄-/OVX animals promotes a reduction in atherosclerotic lesions by reducing ROS and MMP-2 activity and expression.     

Expression of SLC26A9 in Airways and Its Potential Role in Asthma

SLC26A9 is an epithelial anion transporter with a poorly defined function in airways. It is assumed to contribute to airway chloride secretion and airway surface hydration. However, immunohistochemistry showing precise localization of SLC26A9 in airways is missing. Some studies report localization near tight junctions, which is difficult to reconcile with a chloride secretory function of SLC26A9. We therefore performed immunocytochemistry of SLC26A9 in sections of human and porcine lungs. Obvious apical localization of SLC26A9 was detected in human and porcine superficial airway epithelia, whereas submucosal glands did not express SLC26A9. The anion transporter was located exclusively in ciliated epithelial cells. Highly differentiated BCi-NS1 human airway epithelial cells grown on permeable supports also expressed SLC26A9 in the apical membrane of ciliated epithelial cells. BCi-NS1 cells expressed the major Cl⁻ transporting proteins CFTR, TMEM16A and SLC26A9 in about equal proportions and produced short-circuit currents activated by increases in intracellular cAMP or Ca²⁺. Both CFTR and SLC26A9 contribute to basal chloride currents in non-stimulated BCi-NS1 airway epithelia, with CFTR being the dominating Cl⁻ conductance. In wtCFTR-expressing CFBE human airway epithelial cells, SLC26A9 was partially located in the plasma membrane, whereas CFBE cells expressing F508del-CFTR showed exclusive cytosolic localization of SLC26A9. Membrane localization of SLC26A9 and basal chloride currents were augmented by interleukin 13 in wild-type CFTR-expressing cells, but not in cells expressing the most common disease-causing mutant F508del-CFTR. The data suggest an upregulation of SLC26A9-dependent chloride secretion in asthma, but not in the presence of F508del-CFTR.     

Solid Tumors and Kinase Inhibition: Management and Therapy Efficacy Evolution

The increasing numbers of cancer cases worldwide and the exceedingly high mortality rates of some tumor subtypes raise the question about if the current protocols for cancer management are effective and what has been done to improve upon oncologic patients’ prognoses. The traditional chemo-immunotherapy options for cancer treatment focus on the use of cytotoxic agents that are able to overcome neoplastic clones’ survival mechanisms and induce apoptosis, as well as on the ability to capacitate the host’s immune system to hinder the continuous growth of malignant cells. The need to avert the highly toxic profiles of conventional chemo-immunotherapy and to overcome the emerging cases of tumor multidrug resistance has fueled a growing interest in the field of precision medicine and targeted molecular therapies in the last couple of decades, although relatively new alternatives in oncologic practices, the increased specificity, and the positive clinical outcomes achieved through targeted molecular therapies have already consolidated them as promising prospects for the future of cancer management. In recent years, the development and application of targeted drugs as tyrosine kinase inhibitors have enabled cancer treatment to enter the era of specificity. In addition, the combined use of targeted therapy, immunotherapy, and traditional chemotherapy has innovated the standard treatment for many malignancies, bringing new light to patients with recurrent tumors. This article comprises a series of clinical trials that, in the past 5 years, utilized kinase inhibitors (KIs) as a monotherapy or in combination with other cytotoxic agents to treat patients afflicted with solid tumors. The results, with varying degrees of efficacy, are reported.