Most lung diseases are serious conditions resulting from genetic and environmental causes associated with high mortality and severe symptoms. Currently, treatments available have a palliative effect ...and many targets are still considered undruggable. Gene therapy stands as an attractive approach to offering innovative therapeutic solutions. CRISPRCas9 has established a remarkable potential for genome editing with high selectivity to targeted mutations. To ensure high efficacy with minimum systemic exposure, the delivery and administration route are key components that must be investigated.
This review is focused on the delivery of CRISPRCas9 to the lungs, taking advantage of lipid nanoparticles (LNPs), the most clinically advanced nucleic acid carriers. We also aim to highlight the benefits of pulmonary administration as a local delivery route and the use of spray drying to prepare stable nucleic-acid-based dry powder formulations that can overcome multiple lung barriers.
Exploring the pulmonary administration to deliver CRISPRCas9 loaded in LNPs as a dry powder increases the chances to achieve high efficacy and reduced adverse effects. CRISPRCas9 loaded in LNP-embedded microparticles has not yet been reported in the literature but has the potential to reach and accumulate in target cells in the lung, thus, enhancing overall efficacy and safety.
To evaluate the chronic effects of a static stretching program on the muscle architecture of biceps femoris (BF) and vastus lateralis (VL) muscles in ultrasound (US) images.
Randomized controlled ...longitudinal trial.
Biomechanics Laboratory of Physical Education School of the Army, Rio de Janeiro, Brazil.
The study included 24 healthy and physically active male volunteers (19.05 ± 1.40 years, 1.73 ± 0.07 m, and 73.15 ± 8.33 kg), randomly allocated to 1 of 2 groups: stretching group (SG, n = 12) and control group (n = 12).
The SG was submitted to 3 sets of 30 seconds of static stretching 3 times a week during 8 weeks.
Ultrasound equipment (7.5 MHz) was used for the evaluation of BF and VL muscle architecture variables (pennation angle, fiber length, muscle thickness, and fascicle displacement) before and after training. Knee range of motion (ROM) and isometric flexion and extension torque (TQ) were also measured.
There were no significant changes in muscle architecture, TQ, and maximum knee flexion angle (P > 0.05). However, maximum knee extension angle (MEA) increased significantly in the SG (pretraining: 159.37 ± 7.27 degrees and posttraining: 168.9 ± 3.7 degrees; P < 0.05).
Volume or intensity (or both) of the stretching protocol was insufficient to cause structural changes in the VL and BF muscles. The increase in MEA could not be explained by muscle architecture changes.
To describe changes in the VL and BF muscle tendon unit using US after a long-term stretching program to identify which structures are responsible for ROM increase.
Leishmaniasis is an infectious disease responsible for a huge rate of morbidity and mortality in humans. Chemotherapy consists of the use of pentavalent antimonial, amphotericin B, pentamidine, ...miltefosine, and paromomycin. However, these drugs are associated with some drawbacks such as high toxicity, administration by parenteral route, and most seriously the resistance of some strains of the parasite to them. Several strategies have been used to increase the therapeutic index and reduce the toxic effects of these drugs. Among them, the use of nanosystems that have great potential as a site-specific drug delivery system stands out. This review aims to compile results from studies that were carried out using first- and second-line antileishmanial drug-carrying nanosystems. The articles referred to here were published between 2011 and 2021. This study shows the promise of effective applicability of drug-carrying nanosystems in the field of antileishmanial therapeutics, with the perspective of providing better patient adherence to treatment, increased therapeutic efficacy, reduced toxicity of conventional drugs, as well as the potential to efficiently improve the treatment of leishmaniasis.
Sá, MA, Matta, TT, Carneiro, SP, Araujo, CO, Novaes, JS, and Oliveira, LF. Acute effects of different methods of stretching and specific warm-ups on muscle architecture and strength performance. J ...Strength Cond Res 30(8): 2324-2329, 2016-The purpose of the study was to investigate the acute effects of 2 stretching interventions, proprioceptive neuromuscular facilitation (PNF) and passive static stretching (PSS), and a specific warm-up (SW) on the strength and architecture of the vastus laterallis and biceps femoris muscles in a subsequent performance on a strength training session (STS). Musculoskeletal ultrasound images were acquired from 9 men before and immediately after stretchings or a SW, and 10 minutes after a STS. The STS consisted of the following exercises: leg extension, leg curl, leg press, and hack machine squat. The PNF resulted in lower performance for all situations. The PSS and SW improved performance for the leg press compared with the PNF and controls (CSs). For the hack machine squat, SWs resulted in higher performance than stretching conditions. The vastus lateralis muscle fascicle length (FL) increases after a STS for PNF. The biceps femoris muscle showed a higher pennation angle 10 minutes after the STS for PSS; the FL increases immediately after PSS and then decreases 10 minutes after the STS for PSS. As per our results, the SWs should be performed before STSs, whereas PNF stretching should not be prescribed because this condition impairs subsequent performance. These results may assist health professionals in prescribing resistance training.
The triterpenes α- and β-amyrins display important pharmacological activities. As a result of their high hydrophobia, they present low water solubility and reflect poor oral bioavailability. ...Different techniques can be used for the improvement of amyrins solubility, one of them is the use of nanoemulsions. Therefore, the method of direct emulsification was used to develop a nanoemulsion of these triterpenes and the resulting drug delivery system was characterized by an in vitro release assay. Encapsulation efficiency higher than 99% was achieved with total release around 30% in 24 h, which suggests that this system could be useful for the administration of α- and β-amyrins by different routes in an efficient way.
The Amazon suffers from the occurrence of mining along its hydrographic routes, which releases toxic substances into the aquatic environment. The objective of this study was to evaluate the risk of ...contamination by As and Hg that indigenous peoples are exposed to through the consumption of fish in an area impacted by mining activity in the basin of the Curuá and Baú Rivers, Altamira-PA. In total, 55 fish specimens and 30 surface water samples were collected. The decomposition of the fish samples was done by wet method with the use of nitric acid, hydrogen peroxide, and microwaves. The quantification of total mercury (THg) and total arsenic (TAs) was carried out by inductively coupled plasma optical emission spectrometry with vapor generation (VG-ICP OES). The methodology proposed by the U.S. Environmental Protection Agency was used. The results showed that TAs presents safe levels; however, THg presents a sample with levels up to (4.6 µg g-1), exceeding the permitted levels (1 µg g-1). The risk assessment shows that only the consumption of fish, linked to Hg, represents the existence of deleterious risks to indigenous peoples (hazard quotient (HQ)) > 1). Bioaccumulation factor (BAF) in fish represents a risk to indigenous people, because of the Hg’s presence. The study identified that illegal mining activities are responsible for Hg pollution in the Baú and Curuá Rivers. The fish species analyzed can be used as bioindicators of Hg in the rivers, which is relevant for making environmental and public health policy decisions.
B vitamins and polymorphisms in genes coding for enzymes involved in one-carbon metabolism may affect DNA synthesis and methylation and thereby be implicated in carcinogenesis. Previous data on ...vitamins B2 and B6 and genetic polymorphisms other than those involving MTHFR as risk factors for gastric cancer (GC) are sparse and inconsistent. In this case-control study nested within the European Prospective Investigation into Cancer and Nutrition cohort, cases (n = 235) and controls (n = 601) were matched for study center, age, sex, and time of blood sampling. B2 and B6 species were measured in plasma, and the sum of riboflavin and flavin mononucleotide was used as the main exposure variable for vitamin B2 status, whereas the sum of pyridoxal 5'-phosphate, pyridoxal, and 4-pyridoxic acid was used to define vitamin B6 status. In addition, we determined eight polymorphisms related to one-carbon metabolism. Relative risks for GC risk were calculated with conditional logistic regression, adjusted for Helicobacter pylori infection status and smoking status. Adjusted relative risks per quartile (95% confidence interval, P(trend)) were 0.85 (0.72-1.01, 0.06) for vitamin B2 and 0.78 (0.65-0.93, <0.01) for vitamin B6. Both relations were stronger in individuals with severe chronic atrophic gastritis. The polymorphisms were not associated with GC risk and did not modify the observed vitamin-cancer associations. In summary, results from this large European cohort study showed an inverse association between vitamin B2 and GC risk, which is borderline significant, and a significant inverse association between vitamin B6 and GC risk.
Geochemical analyses can provide multiple analytical variables. Accordingly, the generation of large geochemical databases enables imputation studies or analytical estimates of missing values or ...complex measuring. The processing of bauxite is a key step in the production of aluminum, in which the determination of Reactive Silica (RxSiO 2 ) and Available Alumina (AvAl 2 O 3 ) are very relevant. The traditional analytical method for achieving RxSiO 2 has limitations associated with poor repeatability and reproducibility of results. Based on the values from the unsupervised Self-Organizing Maps technique, this study aims to develop, systematically, the imputation of missing grades of the geochemical composition of bauxite samples of a database from three trial projects, for the variables: total Al 2 O 3 ; total SiO 2 ; total Fe 2 O 3 ; and total TiO 2 . Each project was submitted to partial exclusion of AvAl 2 O 3 and RxSiO 2 values, in proportion of 20%, 30%, 40% and 50%, to investigate the SOM technique as imputation method for RxSiO 2 and AvAl 2 O 3 . By comparing the imputed values from the SOM analysis with the original values, SOM technique demonstrated to be an imputation tool capable of obtaining analytical results with up to 50% of missing data. Specifically, the best results demonstrate that AvAl 2 O 3 can be obtained by imputation with a higher correlation than RxSiO 2 , based on the parameters and variables involved in the study. Similarity in the nature of samples and an increase in the number of embedded analytical variables are factors that provided better imputation results.
The low-grade inflammation associated with metabolic syndrome (MS) triggers functional and structural alterations in several organs. Whereas lung function impairment is well reported for older adult ...population, the effect of MS on functional and immunological responses in the lungs remains unclear. In this cross-sectional study we determined whether MS alters pulmonary function, and immunological responses in older adults with MS. The study sample consisted of older adults with MS (68 ± 3 years old; n = 77) and without MS (67 ± 3 years old; n = 77). Impulse oscillometry was used to evaluate airway and tissue resistance, and reactance. Biomarkers of inflammation and fibrosis were assessed in the blood and in breath condensate. The total resistance of the respiratory system (R5Hz; p < 0.009), and the resistance of the proximal (R20Hz; p < 0.001) and distal (R5Hz-R20Hz; p < 0.004) airways were higher in MS individuals compared to those without MS. Pro-inflammatory (leptin, IL-1beta, IL-8, p < 0.001; TNF-alpha, p < 0.04) and anti-inflammatory cytokines (adiponectin, IL-1ra, IL-10, p < 0.001), anti-fibrotic (relaxin 1, relaxin 3, Klotho, p < 0.001) and pro-fibrotic (VEGF, p < 0.001) factors were increased in sera and in breath condensate individuals with MS. The results show that MS adversely affect lung mechanics, function, and immunological response in older adults. The data offer a metabolic basis for the inflammaging of the lungs and suggest the lungs as a potential therapeutic target for controlling the immune response and delaying the onset of impaired lung function in older adults with MS.
To compare the inflammatory and oxidative stress (OS) states of adults with bronchiectasis with those of healthy controls and correlate inflammatory and OS levels with lung function and physical ...capacity.
This study used a cross-sectional design. Seventy-four adults with bronchiectasis (age: 49±15 years, forced expiratory volume in 1 second FEV1: 52.5±25.6%) and 42 healthy controls (age: 44±17 years, FEV1: 95.9±14.0%) performed cardiopulmonary exercise tests and incremental shuttle walking tests. Their physical activity in daily life, inflammatory cytokine, and antioxidant levels in plasma were measured.
Compared to that of the controls, the levels of interleukin (IL)-6 (p<0.001), IL-10 (p<0.001), carbonylated proteins (p=0.001), and superoxide anions (p=0.046) were significantly increased in adults with bronchiectasis. Catalase activity was also reduced in this group (p<0.001). The inflammatory markers IL-1β, IL-6, and tumor necrosis factor-α correlated negatively with aerobic capacity (r=-0.408, r=-0.308, and r=-0.207, respectively). We observed similar correlations with OS markers (thiobarbituric acid and carbonyls; r=-0.290 and r=0.379, respectively), and these markers also significantly correlated with the aerobic capacity.
Adults with bronchiectasis presented an increased systemic inflammatory response that correlated negatively with physical capacity.
PDF
