Purpose
Early weaning (EW) is a stressful condition that programmes a child to be overweight in adult life. Fat mass depends on glucocorticoids (GC) to regulate adipogenesis and lipogenesis. We ...hypothesised that the increased adiposity in models of EW was due to a disturbed HPA axis and/or disrupted GC function.
Methods
We used two experimental models, pharmacological early weaning (PEW, dams were bromocriptine-treated) and non-pharmacological early weaning (NPEW, dams’ teats were wrapped with a bandage), which were initiated during the last 3 days of lactation. Offspring from both genders was analysed on postnatal day 180.
Results
Offspring in both models were overweight with increased visceral fat mass, but plasma corticosterone was increased in both genders in the PEW group but not the NPEW group. NPEW males had increased GRα expression in visceral adipose tissue (VAT), and GRα expression decreased in PEW males in subcutaneous adipose tissue (SAT). Females in both EW groups had increased 11βHSD1 expression in SAT. PEW males had increased C/EBPβ expression in SAT. PEW females had lower PPARy and FAS expression in VAT than the NPEW females. We detected a sex dimorphism in VAT and SAT in the EW groups regarding 11βHSD1, GRα and C/EBPβ expression.
Conclusions
The accumulated adiposity induced by EW exhibited distinct mechanisms depending on gender, specific fat deposition and GC metabolism and action. The higher proportion of VAT/SAT in both sets of EW males may be related to the action of GC in these tissues, and the higher conversion of GC in SAT in females may explain the differences in the fat distribution.
Overexpression of P‐glycoprotein (P‐gp) contributes to the multidrug resistance (MDR) phenotype found in many cancer cells. P‐gp has been identified as a promising molecular target, although attempts ...to find successful therapies to counteract its function as a drug efflux pump have largely failed to date. Apart from its role in drug efflux, P‐gp may have other cellular functions such as being involved in apoptosis, and is found in various locations in the cell. Its expression is highly regulated, namely by microRNAs (miRNAs or miRs). In addition, P‐gp may regulate the expression of miRs in the cell. Furthermore, both P‐gp and miRs may be found in microvesicles or exosomes and may be transported to neighboring, drug‐sensitive cells. Here, we review this current issue together with recent evidence of this network of interactions between P‐gp and miRs.
Maternal smoking increases obesogenesis in the progeny. Obesity is associated with several hormonal dysfunctions. In a rat model of postnatal tobacco smoke exposure, we previously reported increased ...central fat depot and disruption of some hormonal systems in the adult offspring. As both glucocorticoids and vitamin D alter lipogenesis and adipogenesis, here we evaluated the metabolism of these two hormones in visceral adipose tissue (VAT) and liver by Western blotting, and possible associations with lipogenesis biomarkers in adult rats that were exposed to tobacco smoke during their suckling period. At postnatal day (PN) 3, dams and offspring of both sexes were exposed (S group) or not (C group) to tobacco smoke, 4 × 1 h/day. At PN180, corticosteronemia was lower in S male and higher in S female offspring, without alterations in peripheral glucocorticoid metabolism and receptor. Adrenal ACTH receptor (MC2R) was higher in both sexes of S group. Despite unchanged serum vitamin D, liver 25-hydroxylase was higher in both sexes of S group. Male S offspring had higher 1α-hydroxylase, acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS) in VAT. Both sexes showed increased ACC protein content and reduced sirtuin mRNA in liver. Male S offspring had lower liver peroxisome proliferator-activated receptor-α. Tobacco exposure during lactation induced abdominal obesity in both sexes via distinct mechanisms. Males and females seem to develop HPA-axis dysfunction instead of changes in glucocorticoid metabolism and action. Lipogenesis in VAT and liver, as well as vitamin D status, are more influenced by postnatal smoke exposure in male than in female adult rat offspring.
Inspiratory muscle function may be affected in patients with End-Stage Renal Disease (ESRD), further worsening the functional loss in these individuals. However, the impact of inspiratory muscle ...weakness (IMW) on the functional capacity (FC) of hemodialysis patients remains unknown. Thus, the present study aimed to evaluate the impact of IMW on FC in ESRD patients undergoing hemodialysis.
ESRD patients on hemodialysis treatment for more than six months were evaluated for inspiratory muscle strength and FC. Inspiratory muscle strength was evaluated based on maximal inspiratory pressure (MIP). IMW was defined as MIP values less than 70% of the predicted value. FC was evaluated using the Incremental Shuttle Walk test (ISWT). Patients whose predicted peak oxygen uptake (VO2peak) over the distance walked during the ISWT was less than 16mL/kg/min were considered to have FC impairment. Associations between variables were assessed by linear and logistic regression, with adjustment for age, sex, body mass index (BMI), presence of diabetes and hemoglobin level. Receiver-operating characteristic (ROC) analysis was used to determine different cutoff values of the MIP for normal inspiratory muscle strength and FC.
Sixty-five ERSD patients (67.7% male), aged 48.2 (44.5-51.9) years were evaluated. MIP was an independent predictor of the distance walked during the ISWT (R2 = 0.44). IMW was an independent predictor of VO2peak < 16mL/kg/min. (OR = 5.7; p = 0.048) in adjusted logistic regression models. ROC curves showed that the MIP cutoff value of 82cmH2O had a sensitivity of 73.5% and specificity of 93.7% in predicting normal inspiratory strength and a sensitivity and specificity of 76.3% and 70.4%, respectively, in predicting VO2peak ≥ 16mL/kg/min.
IMW is associated with reduced FC in hemodialysis patients. Evaluation of the MIP may be important to functional monitoring in clinical practice and can help in the stratification of patients eligible to perform exercise testing.
The gut microbiota affects the host's metabolic phenotype, impacting health and disease. The gut‐brain axis unites the intestine with the centers of hunger and satiety, affecting the eating behavior. ...Deregulation of this axis can lead to obesity onset. Litter size reduction is a well‐studied model for infant obesity because it causes overnutrition and programs for obesity. We hypothesize that animals raised in small litters (SL) have altered circuitry between the intestine and brain, causing hyperphagia. We investigated vagus nerve activity, the expression of c‐Fos, brain‐derived neurotrophic factor (BDNF), gastrointestinal (GI) hormone receptors, and content of bacterial phyla and short‐chain fatty acids (SCFAs) in the feces of adult male and female Wistar rats overfed during lactation. On the 3rd day after birth, litter size was reduced to 3 pups/litter (SL males or SL females) until weaning. Controls had normal litter size (10 pups/litter: 5 males and 5 females). The rats were killed at 5 months of age. The male and female offspring were analyzed separately. The SL group of both sexes showed higher food consumption and body adiposity than the respective controls. SL animals presented dysbiosis (increased Firmicutes, decreased Bacteroidetes) and had increased vagus nerve activity. Only the SL males had decreased hypothalamic GLP‐1 receptor expression, while only the SL females had lower acetate and propionate in the feces and higher CCK receptor expression in the hypothalamus. Thus, overfeeding during lactation differentially changes the gut‐brain axis, contributing to hyperphagia of the offspring of both sexes.
Litter size reduction causes vagal hyperactivity in both sexes at adulthood. Both sexes presented gut dysbiosis. Early overfeeding is able to program parameters of the gut‐brain axis and impact the eating pattern in adult life.
To evaluate the test-retest reliability and validity of the Patient Generated Index (PGI) in individuals with Chronic Kidney Disease (CDK) undergoing hemodialysis.
Through a non-experimental study ...with repeated measures, PGI was applied twice to assess internal consistency and test-retest reliability. Correlations with the Kidney Disease Quality of Life Short Form (KDQOL-SF), the Human Activity Profile (HAP) questionnaire, the Social Participation Scale, and the Glittre ADL Test were used.
91 individuals with CKD were evaluated. There was high reliability for the PGI (ICC= 0.97) PGI correlated with KQDOL - SF in Functional Capacity r = 0.38 (p < 0.001), Emotional Well-Being r = 0.31 (p = 0.003), Social Aspect r = 0.22 (p = 0.036), Emotional Function r = 0.22 (p = 0.038) and Effect of Kidney Disease r = 0.21 (p = 0.042), and Physical scores r = 0.24 (p = 0.021)), Mental r = 0.21 (p = 0.05) and General r = 0.22 (p = 0.037) summarized. There was a significant correlation between PGI and HAP r = 0.40 (p < 0.001) and the Social Participation Scale r = −0.36 (p < 0.001). There was no correlation between the PGI and Glittre ADL scores r = 0.12 (p = 0.247).
In adults receiving hemodialysis, the PGI proved to be an accurate and reliable instrument for the assessment of the quality of life from the perspective of the patient.
IMPLICATIONS FOR REHABILITATION
Although hemodialysis treatment is associated with increased survival and symptom control, there is a significant change in the patient's lifestyle.
In order to provide a more focused view of the individual, the Patient Generated Index (PGI) was created to evaluate the quality of life.
PGI is reliable and correlates with KQDOL - SF and the Social Participation Scale in this population.
To investigate the validity and within-day reliability of the Glittre activities of daily living test (Glittre ADL-test) in patients on hemodialysis.
Ninety-one patients on hemodialysis were ...evaluated using Glittre ADL-test, functional tests, health-related quality of life, human activity profile, and social participation. Convergent validity was analyzed by the correlation analysis. The Glittre ADL-test results were compared among different levels of the functional tests, human activity profile, and participation (known-groups validity). Within-day reliability was examined by Intra-class Correlation Coefficient (ICC).
There was a significant moderate to strong correlation between Glittre ADL-test and functional tests (r = 0.62 to 0.66 and −0.70 to −0.44). A significant weak correlation was found between Glittre ADL-test, health-related quality of life (r = 0.28 to 0.32), and human activity profile (r=−0.33). There was no significant correlation with participation. Except for participation level, the Glittre ADL-test results were able to identify individuals with low performance in all evaluated tests and were able to differentiate among inactive and active individuals by human activity profile (p < 0.05). Within-day reliability was evaluated in 42 patients. The ICC was 0.97.
The Glittre ADL-test is a reliable test associated with functional parameters and physical aspects related to health-related quality of life, with potential value in the functional evaluation of patients on hemodialysis.
Implications for rehabilitation
Functional impairment is a common clinical finding and is an important predictor of poor prognosis in patients on hemodialysis.
The Glittre ADL-test has excellent within-day reliability and is a valid instrument for functional assessment in patients on hemodialysis.
Activity limitations of patients on hemodialysis can be assessed by Glittre ADL-test.
Mayaro virus (MAYV) is a sublethal arbovirus transmitted by mosquitoes with possible installation of an urban cycle in the Americas. Its infection causes disabling arthralgia, and still, there is no ...vaccine or treatment to it. We recently investigated nearly 600 compounds by molecular docking and identified epicatechin as a potent antiviral against MAYV. The root extract of Maytenus imbricata showed anti-MAYV activity and two isolated compounds from this plant were also evaluated in vitro. Proanthocyanidin (PAC), a dimer containing epicatechin, showed an effective concentration for 50% of the cells infected by MAYV (EC50) of 37.9 ± 2.4 μM and a selectivity index (SI) above 40. PAC showed significant virucidal activity, inhibiting 100% of the virus proliferation (7 log units), and caused moderate effect during adsorption and virus internalization stage. However, PAC was unable to block the infection when only the cells were pretreated. It was observed a reduction in virus yields when adding PAC at different moments after infection. The set of results indicates that PAC binds to viral and non-cellular elements and may inactivate the MAYV. The inactivation occurs before infection or when the virus reaches the extracellular environment from the 2nd cycle of infection that could block its progression cell-to-cell or to tissues not yet infected.
•Proanthocyanidin (PAC) was able to inhibit Mayaro virus infection with SI greater than 40.•PAC, a dimer methylepigallocatechin and epicatechin, has much greater antiviral activity than monomeric forms.•The dimeric form also reduced cytotoxicity, improving therefore its selectivity.
To verify the effect of the Pact for Health on premature mortality (30-69 years) attributed to cervical cancer in Brazil and its macroregions, using interrupted time series analysis.
Segmented ...regression was used to assess "change in level" and "change in trend" in premature mortality rates attributed to cervical cancer considering the post-Pact period (2010-2018), controlling by the pre-Pact period (1998-2006). Understanding the triennium 2007-2009 as essential for the adoption and implementation of the policy, it was excluded from the main modeling, but assessed in the sensitivity analysis.
From 1998 to 2018, there were more than 119,000 deaths due to cervical cancer in women aged 30 to 69 years in Brazil. The Northern region experienced the highest rates (> 20 per 100,000). Comparing with baseline (1998-2006), segmented regression showed a progressive increase in changing trend from cervical cancer deaths in Brazil as a whole (coefficient = 0.513; 95%CI 0.430 to 0.596) and in the Southeast region (coefficient = 0.515; 95%CI 0.358 to 0.674), South region (coefficient = 0.925; 95%CI 0.642 to 1.208), and Midwest region (coefficient = 0.590; 95%CI 0.103 to 1.077). The Northeast region presented the most promising effects with immediate reduction in change level (-0.635; 95%CI -1.177 to -0.092) and progressive reduction in the changing trend of premature deaths (coefficient= -0.151; 95%CI -0.231 to -0.007).
Premature mortality rates due to cervical cancer are high in Brazil and its macroregions. This interrupted time series was not able to reveal the effectiveness of initiatives related to the Pact for Health on premature deaths from cervical cancer nationally and in all macroregions equally. The best results are restricted to the Northeast region.
Multidrug resistance (MDR) presents a serious challenge to the efficiency of cancer treatment, and may be associated with the overexpression of drug efflux pumps. P-glycoprotein (P-gp) is a drug ...efflux pump often found overexpressed in cases of acquired MDR. Nevertheless, there are no P-gp inhibitors being used in the current clinical practice, due to toxicity problems, drug interactions, or pharmacokinetic issues. Therefore, it is important to identify novel inhibitors of P-gp activity or expression. Curcumin is a secondary metabolite isolated from the turmeric of
L. which has been associated with several biological activities, particularly P-gp modulatory activity (by inhibiting both P-gp function and expression). However, curcumin shows extensive metabolism and instability, which has justified the recent and intensive search for analogs of curcumin that maintain the P-gp modulatory activity but have enhanced stability. This review summarizes and compares the effects of curcumin and several curcumin analogs on P-glycoprotein function and expression, emphasizing the potential of these molecules for the possible development of safe and effective inhibitors of P-gp to overcome MDR in human cancer.
PDF
