Effects of superparamagnetic iron oxide nanoparticles (SPIONS) testicular injection on Leydig cell function and sperm production in a murine model.

In the domain of medical advancement, nanotechnology plays a pivotal role, especially in the synthesis of biocompatible materials for therapeutic use. Superparamagnetic Iron Oxide Nanoparticles (SPIONs), known for their magnetic properties and low toxicity, stand at the forefront of this innovation. This study explored the reproductive toxicological effects of Sodium Citrate-functionalized SPIONs (Cit_SPIONs) in adult male mice, an area of research that holds significant potential yet remains largely unknown. Our findings reveal that Cit_SPIONs induce notable morphological changes in interstitial cells and the seminiferous epithelium when introduced via intratesticular injection. This observation is critical in understanding the interactions of nanomaterials within reproductive biological systems. A striking feature of this study is the rapid localization of Cit_SPIONs in Leydig cells post-injection, a factor that appears to be closely linked with the observed decrease in steroidogenic activity and testosterone levels. This data suggests a possible application in developing nanostructured therapies targeting androgen-related processes. Over 56 days, these nanoparticles exhibited remarkable biological distribution in testis parenchyma, infiltrating various cells within the tubular and intertubular compartments. While the duration of spermatogenesis remained unchanged, there were many Tunel-positive germ cells, a notable reduction in daily sperm production, and reduced progressive sperm motility in the treated group. These insights not only shed light on the intricate mechanisms of Cit_SPIONs interaction with the male reproductive system but also highlight the potential of nanotechnology in developing advanced biomedical applications.

Combination of Aerobic Training and Cocoa Flavanols as Effective Therapies to Reduce Metabolic and Inflammatory Disruptions in Insulin-Resistant Rats: The Exercise, Cocoa, and Diabetes Study.

We aimed to investigate the combined effects of aerobic exercise (EXE) and cocoa flavanol (COCOA) supplementation on performance, metabolic parameters, and inflammatory and lipid profiles in obese insulin-resistant rats. Therefore, 32 male Wistar rats (230-250 g) were fed a high-fat diet and a fructose-rich beverage for 30 days to induce insulin resistance. Next, the rats were randomized into four groups, orally administered placebo solution or COCOA supplementation (45 mg·kg-1), and either remained sedentary or were subjected to EXE on a treadmill at 60% peak velocity for 30 min, for 8 weeks. Blood samples and peripheral tissues were collected and processed to analyze metabolic and inflammatory parameters, lipid profiles, and morphological parameters. Supplementation with COCOA and EXE improved physical performance and attenuated body mass gain, adipose index, and adipocyte area. When analyzed as individual interventions, supplementation with COCOA and EXE improved glucose intolerance and the lipid profile reduced the concentrations of leptin, glucose, and insulin, and reduced homeostasis assessment index (all effects were p < .001 for both interventions), while ameliorated some inflammatory mediators in examined tissues. In skeletal muscles, both COCOA supplementation and EXE increased the expression of glucose transporter (p < .001 and p < .001), and combined intervention showed additive effects (p < .001 vs. COCOA alone or EXE alone). Thus, combining COCOA with EXE represents an effective nonpharmacological strategy to treat insulin resistance; it could prevent Type 2 diabetes mellitus by improving physical performance, glucose metabolism, neuroendocrine control, and lipid and inflammatory mediators in the liver, pancreas, adipose tissue, and skeletal muscle in obese male insulin-resistant rats.

Neurological Characteristics of Pediatric Glycogen Storage Disease.

Glycogen storage diseases (GSD) encompass a group of rare inherited diseases due dysfunction of glycogen metabolism. Hypoglycemia is the most common primary manifestation of GSD, and disturbances in glucose metabolism can cause neurological damage. The aims of this study were to first investigate the metabolic, genetic, and neurological profiles of children with GSD, and to test the hypothesis whether GSD type I would have greater neurological impact than GSD type IX. A cross-sectional study was conducted with 12 children diagnosed with GSD [Types: Ia (n=5); 1, Ib (n=1); 4, IXa (n=5); and 1, IXb (n=1)]. Genetic testing was conducted for the following genes using multigene panel analysis. The biochemical data and magnetic resonance imaging of the brain presented by the patients were evaluated. The criteria of adequate metabolic control were adopted based on the European Study on Glycogen Storage Disease type I consensus. Pathogenic mutations were identified using multigene panel analyses. The mutations and clinical chronology were related to the disease course and neuroimaging findings. Adequate metabolic control was achieved in 67% of patients (GSD I, 43%; GSD IX, 100%). Fourteen different mutations were detected, and only two co-occurring mutations were observed across families (G6PC c.247C>T and c.1039C>T). Six previously unreported variants were identified (5 PHKA2; 1 PHKB). The proportion of GSD IX was higher in our cohort compared to other studies. Brain imaging abnormalities were more frequent among patients with GSD I, early-symptom onset, longer hospitalization, and inadequate metabolic control. The frequency of mutations was similar to that observed among the North American and European populations. None of the mutations observed in PHKA2 have been described previously. Therefore, current study reports six GSD variants previously unknown, and neurological consequences of GSD I. The principal neurological impact of GSD appeared to be related to inadequate metabolic control, especially hypoglycemia.

Longitudinal effects of biopsychosocial variables on physical activity after menarche.

BACKGROUND: The aim of the current study is to analyze the longitudinal effects of certain biopsychosocial variables (socioeconomic status, Body Mass Index (BMI), body image and well-being (QL)), measured at three different menarche stages (S1: before menarche, S2: soon after menarche, and S3: one year after S2), on physical activity and inactivity levels in early adolescence. METHODS: The sample comprised 136 Brazilian teenagers (10-13 years old), showing BMI 18.98 kg/m2 at the initial assessment, who voluntarily participated in the study. Data concerning the following variables were collected in 2010 (S1), 2011 (S2) and 2012 (S3): family income (FI) (socioeconomic anamnesis), BMI (body mass and height), well-being (Autoquestionnaire Qualité de Vie Enfant Imagé) and body image (Body Shape Questionnaire). The physical activity and inactivity levels were measured in S3, only, through the International Physical Activity Questionnaire. The Pearson's correlation and the longitudinal path analysis technique were used to statistically analyze the data. RESULTS: The main results indicated that only family income and BMI, measured soon after menarche (S2), showed significant effect on physical activity and inactivity levels. More specifically, family income has positively influenced (ß=0.25) physical inactivity levels and negatively influenced (ß=-0.14) moderate physical activity levels, whereas BMI has positively influenced (ß=0.15) walking levels and negatively influenced (ß=-0.13) vigorous physical activity levels. CONCLUSIONS: These results suggest that the body image and well-being perceived by the teenagers at different menarche stages are not determining factors of their physical activity levels in early adolescence. On the other hand, the effects of socioeconomic status and BMI on early adolescent girls' physical activity and inactivity levels depend on the assessment period.

Neurodevelopmental regression, severe generalized dystonia, and metabolic acidosis caused by POLR3A mutations.

OBJECTIVE: To expand the clinical phenotype of POLR3A mutations by assessing the functional consequences of a missense and a splicing acceptor mutation. METHODS: We performed whole-exome sequencing for identification of likely pathogenic mutations in a 9-year-old female patient with severe generalized dystonia, metabolic acidosis, leukocytosis, hypotonia, and dysphagia. Brain MRI showed basal ganglia atrophy and presence of lactate and lipid peaks by [1H]-magnetic resonance spectroscopy. Expression levels of Pol III target genes were measured by quantitative real-time (qRT)-PCR to study the pathogenicity of the biallelic mutations in patient fibroblasts. RESULTS: The patient is a compound heterozygous for a novel missense c.3721G>A (p.Val1241Met) and the splicing region c.1771-6C>G mutation in POLR3A, the gene coding for the catalytic subunit of RNA polymerase III (Pol III). Aberrant splicing was observed for the c.1771-6C>G mutation. Decreased RNA expression levels of Pol III targets (HNRNPH2, ubiquitin B, lactotransferrin, and HSP90AA1) were observed in patient fibroblasts with rescue to normal levels by overexpression of the wild-type protein but not by the p.Val1241Met variant. CONCLUSIONS: Mutations in the POLR3A gene cause POLR3A-related hypomyelinating leukodystrophy with or without oligodontia or hypogonadotropic hypogonadism (HLD7, OMIM: 607694) and neonatal progeroid syndrome (OMIM: 264090), both with high phenotypic variability. We demonstrated the pathogenicity of c.1771-6C>G and c.3721G>A mutations causing an early-onset disorder. The phenotype of our patient expands the clinical presentation of POLR3A-related mutations and suggests a new classification that we propose designating as Neurodevelopmental Disorder with Regression, Abnormal Movements, and Increased Lactate.

An optimized nanoparticle delivery system based on chitosan and chondroitin sulfate molecules reduces the toxicity of amphotericin B and is effective in treating tegumentary leishmaniasis.

Amphotericin B (AmpB) is active against leishmaniasis, but its use is hampered due to its high toxicity observed in patients. In this study, a nanoparticles-delivery system for AmpB (NQC-AmpB), containing chitosan and chondroitin sulfate molecules, was evaluated in BALB/c mice against Leishmania amazonensis. An in vivo biodistribution study, including biochemical and toxicological evaluations, was performed to evaluate the toxicity of AmpB. Nanoparticles were radiolabeled with technetium-99m and injected in mice. The products presented a similar biodistribution in the liver, spleen, and kidneys of the animals. Free AmpB induced alterations in the body weight of the mice, which, in the biochemical analysis, indicated hepatic and renal injury, as well as morphological damage to the kidneys of the animals. In general, no significant organic alteration was observed in the animals treated with NQC-AmpB. Mice were infected with L. amazonensis and treated with the nanoparticles or free AmpB; then, parasitological and immunological analyses were performed. The NQC-AmpB group, as compared to the control groups, presented significant reductions in the lesion size and in the parasite burden in all evaluated organs. These animals presented significantly higher levels of IFN-γ and IL-12, and low levels of IL-4 and IL-10, when compared to the control groups. The NQC-AmpB system was effective in reducing the infection in the animals, and proved to be effective in diminishing the toxicity evoked by AmpB, which was observed when it was administered alone. In conclusion, NQC-AmpB could be considered a viable possibility for future studies in the treatment of leishmaniasis.

Neurodegenerative disorders increase decline in respiratory muscle strength in older adults.

INTRODUCTION: Respiratory muscle strength (RMS) is a determinant of vital capacity, and its decline can lead to inadequate ventilation and deficiency in the elimination of secretions from the airways. Studies analyzing RMS in older adults with Parkinson's disease (PD) and Alzheimer's disease (AD) remain scarce, making the analysis of this variable still very uncertain. The aim of this study was to analyze the RMS of older adults diagnosed with PD and AD, in relation to healthy control peers. METHODS: A cross-sectional study was conducted involving 65 older adults comprising 3 groups: PD (n = 20), AD (n = 20), and control (n = 25). The participants underwent anthropometric and cirtometric measurements associated with maximal respiratory pressures. We analyzed data using descriptive (mean and SD) and inferential statistics (1-way analysis of variance, Student t test, and Scheffé post hoc) with a level of significance of 5% (P < .05) and a CI of 95%. RESULTS: Although the anthropometric and cirtometric variables indicated similarity of values between groups (P > .05), the maximal inspiratory and expiratory pressures were considerably lower in the subjects with PD and AD (P < .01). CONCLUSIONS: The control of the anthropometric and cirtometric variables of the subjects indicates that RMS is affected by the aging process, and its decline increases in neurodegenerative conditions. This fact represents a serious risk for the development of atelectasis and other pneumo-functional complications, which must be considered in proposing of future therapies.

Body dissatisfaction and self-esteem in female students aged 9-15: the effects of age, family income, body mass index levels and dance practice.

This study aimed to analyze the effects of age, family income, body mass index and dance practice on levels of body dissatisfaction and self-esteem in female students. The sample consisted of 283 female subjects attending a public school with a mean age of 11.51±1.60 years and a mean body mass index of 18.72 kg/m2 (SD=3.32). The instruments used were the Body Dissatisfaction Scale for Adolescents and the Rosenberg Self-Esteem Scale, both of which showed good internal consistency (0.77 and 0.81, respectively). The tests were applied (two-factor ANOVA) to compare the students practicing and those not practicing dance; the differences in the levels of body dissatisfaction (p=0.104) and self-esteem (p=0.09) were considered significant. The results demonstrated that age negatively correlated with body dissatisfaction (r=-0.19; p<0.01) and that higher body mass index levels were associated with greater body dissatisfaction (r=0.15, p=0.016) and lower levels of self-esteem (r=-0.17, p<0.01) only in non-practitioners. The practice of dance had a significant effect on levels of body dissatisfaction (F=4.79; p=0.030; η(2)=0.02), but there was no significant difference in self-esteem (F=1.88; p=0.172; η(2)=0.02). It can be concluded that female children and adolescents practicing dance have higher self-esteem, and are more satisfied with their body weight and their appearance. Moreover, results showed that self-esteem and body dissatisfaction were influenced by the body mass index levels only in the non-practitioners group.

TGF-beta1 system in Leydig cells. Part II: TGF-beta1 and progesterone, through Smad1/5, are involved in the hyperplasia/hypertrophy of Leydig cells.

Several reports indicate that transforming growth factor beta1 (TGF-beta1) participates in the regulation of cell cycle progression. In this work, we analyzed the in vitro effect of TGF-beta1 on Leydig cell proliferation markers and the in vivo effect of this cytokine in Leydig cell hyperplasia/hypertrophy. The in vitro effect of TGF-beta1 (1 ng/ml) plus progesterone (10(-6) M) on purified Leydig cells from 3 week-old mice increased the immunocytochemically detected PCNA and stimulated the phosphorylation of Smad 1/5. Progesterone (10(-6) M) in the presence or absence of TGF-beta1 diminished the ratio Bax/Bcl-2. Morphometric testicular studies of mice treated with progesterone (s.c.) plus TGF-beta1 (intratesticular), showed an increase in interstitial volume and a decrease in tubular volume. Furthermore, the cytoplasmic volume of Leydig cells showed an increment in this experimental group with a diminution in nuclear volume. Thus, it turned out that the administration of progesterone and TGF-beta1 augmented the volume of Leydig cells. These results indicate a clear effect of TGF-beta1 in the hypertrophy/hyperplasia of Leydig cells.

Mucopolysaccharidosis I, II, and VI: Brief review and guidelines for treatment.

Mucopolysaccharidoses (MPS) are rare genetic diseases caused by the deficiency of one of the lysosomal enzymes involved in the glycosaminoglycan (GAG) breakdown pathway. This metabolic block leads to the accumulation of GAG in various organs and tissues of the affected patients, resulting in a multisystemic clinical picture, sometimes including cognitive impairment. Until the beginning of the XXI century, treatment was mainly supportive. Bone marrow transplantation improved the natural course of the disease in some types of MPS, but the morbidity and mortality restricted its use to selected cases. The identification of the genes involved, the new molecular biology tools and the availability of animal models made it possible to develop specific enzyme replacement therapies (ERT) for these diseases. At present, a great number of Brazilian medical centers from all regions of the country have experience with ERT for MPS I, II, and VI, acquired not only through patient treatment but also in clinical trials. Taking the three types of MPS together, over 200 patients have been treated with ERT in our country. This document summarizes the experience of the professionals involved, along with the data available in the international literature, bringing together and harmonizing the information available on the management of these severe and progressive diseases, thus disclosing new prospects for Brazilian patients affected by these conditions.

Mucopolysaccharidosis I, II, and VI: brief review and guidelines for treatment

Mucopolysaccharidoses (MPS) are rare genetic diseases caused by the deficiency of one of the lysosomal enzymes involved in the glycosaminoglycan (GAG) breakdown pathway. This metabolic block leads to the accumulation of GAG in various organs and tissues of the affected patients, resulting in a multisystemic clinical picture, sometimes including cognitive impairment. Until the beginning of the XXI century, treatment was mainly supportive. Bone marrow transplantation improved the natural course of the disease in some types of MPS, but the morbidity and mortality restricted its use to selected cases. The identification of the genes involved, the new molecular biology tools and the availability of animal models made it possible to develop specific enzyme replacement therapies (ERT) for these diseases. At present, a great number of Brazilian medical centers from all regions of the country have experience with ERT for MPS I, II, and VI, acquired not only through patient treatment but also in clinical trials. Taking the three types of MPS together, over 200 patients have been treated with ERT in our country. This document summarizes the experience of the professionals involved, along with the data available in the international literature, bringing together and harmonizing the information available on the management of these severe and progressive diseases, thus disclosing new prospects for Brazilian patients affected by these conditions.