Abstract
Extracellular vesicles (EVs) are mediators of the immune system response. Encapsulated in EVs, microRNAs can be transferred between cancer and immune cells. To define the potential effects ...of EVs originated from squamous cell carcinoma cells on immune system response, we performed microRNA profiling of EVs released from two distinct cell lines and treated dendritic cells derived from circulating monocytes (mono-DCs) with these EVs. We confirmed the internalization of EVs by mono-DCs and the down-regulation of microRNA mRNA targets in treated mono-DCs. Differences in surface markers of dendritic cells cultivated in the presence of EVs indicated that their content disrupts the maturation process. Additionally, microRNAs known to interfere with dendritic cell function, and detected in EVs, matched microRNAs from squamous cell carcinoma patients’ plasma: miR-17-5p in oropharyngeal squamous cell carcinoma, miR-21 in oral squamous cell carcinoma, miR-16, miR-24, and miR-181a circulating in both oral and oropharyngeal squamous cell carcinoma, and miR-23b, which has not been previously described in plasma of head and neck squamous cell carcinoma, was found in plasma from patients with these cancer subtypes. This study contributes with insights on EVs in signaling between cancer and immune cells in squamous cell carcinoma of the head and neck.
The majority of groceries purchased by US households are industrially processed, yet it is unclear how processing level influences diet quality. We sought to determine if processing level is ...associated with diet quality of grocery purchases.
We analysed grocery purchasing data from the National Household Food Acquisition and Purchase Survey 2012-2013. Household grocery purchases were categorized by the NOVA framework as minimally processed, processed culinary ingredients, processed foods or ultra-processed foods. The energy share of each processing level (percentage of energy; %E) and Healthy Eating Index-2015 (HEI-2015) component and total scores were calculated for each household's purchases. The association between %E from processed foods and ultra-processed foods, respectively, and HEI-2015 total score was determined by multivariable linear regression. Foods purchased by households with the highest v. lowest ultra-processed food purchases and HEI-2015 total score <40 v. ≥60 were compared using linear regression.
USA.
Nationally representative sample of 3961 households.
Processed foods and ultra-processed foods provided 9·2 (se 0·3) % and 55·8 (se 0·6) % of purchased energy, respectively. Mean HEI-2015 score was 54·7 (se 0·4). Substituting 10 %E from minimally processed foods and processed culinary ingredients for ultra-processed foods decreased total HEI-2015 score by 1·8 points (β = -1·8; 95 % CI -2·0, -1·5). Processed food purchases were not associated with diet quality. Among households with high ultra-processed food purchases, those with HEI-2015 score <40 purchased less minimally processed plant-foods than households with HEI-2015 score ≥60.
Increasing purchases of minimally processed foods, decreasing purchases of ultra-processed foods and selecting healthier foods at each processing level may improve diet quality.
Herein, we report a case of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and dengue coinfection, presented as a fatal stroke in our hospital, in São José do Rio Preto, São Paulo ...State, a Brazilian city hyperendemic for dengue viruses and other arthropod‐borne viruses (arboviruses) and currently facing a surge of SARS‐CoV‐2 cases. This case is the first described in the literature and contributes to the better understanding of clinical presentations of two important diseases in a tropical setting.
Background:
Impaired stress resilience and a dysfunctional hypothalamic-pituitary-adrenal (HPA) axis are suggested to play key roles in the pathophysiology of illness progression in bipolar disorder ...(BD), but the mechanisms leading to this dysfunction have never been elucidated. This study aimed to examine HPA axis activity and underlying molecular mechanisms in patients with BD and unaffected siblings of BD patients.
Methods:
Twenty-four euthymic patients with BD, 18 siblings of BD patients, and 26 healthy controls were recruited for this study. All subjects underwent a dexamethasone suppression test followed by analyses associated with the HPA axis and the glucocorticoid receptor (GR).
Results:
Patients with BD, particularly those at a late stage of illness, presented increased salivary post-dexamethasone cortisol levels when compared to controls (p = 0.015). Accordingly, these patients presented reduced ex vivo GR responsiveness (p = 0.008) and increased basal protein levels of FK506-binding protein 51 (FKBP51, p = 0.012), a co-chaperone known to desensitize GR, in peripheral blood mononuclear cells. Moreover, BD patients presented increased methylation at the FK506-binding protein 5 (FKBP5) gene. BD siblings presented significantly lower FKBP51 protein levels than BD patients, even though no differences were found in FKBP5 basal mRNA levels.
Conclusions:
Our data suggest that the epigenetic modulation of the FKBP5 gene, along with increased FKBP51 levels, is associated with the GR hyporesponsiveness seen in BD patients. Our findings are consistent with the notion that unaffected first-degree relatives of BD patients share biological factors that influence the disorder, and that such changes are more pronounced in the late stages of the illness.
In this study, the effect of the ionic cross-linking mode on the ability to control physical properties and in vitro release behavior of the dexamethasone (DEX) drug from chitosan (CS) and ...chitosan/hydroxyapatite (CS/HA) beads was investigated. CS solutions without and with HA and DEX were dripped into two coagulation solutions, prepared with a non-toxic ionic crosslinker (sodium tripolyphosphate, TPP) and distilled water, one at pH = 9.0 and other at pH = 6.0. Optical microscopy (OM) and scanning electron microscopy (SEM) results showed changes on the surface topology of the beads, with a reduction of roughness for beads prepared at pH = 6.0 and an increase for the one prepared at pH = 9.0. The diameter and sphericity of the beads prepared at pH = 6.0 proved more uniform and had a larger pore size with a good interconnectivity framework. Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) suggested a higher crosslinking degree for beads prepared at pH = 6.0, corroborated by X-ray diffraction profiles (XRD) analysis that indicated a decrease in the crystalline structure for such beads. In in vitro drug release data, all beads presented a sustained release during the studied period (24 h). The drug release rate was affected by the pH of the coagulation solution used in the preparation of the beads. The in vitro kinetics of the release process was of the Peppas-Sahlin model, controlled by both diffusion and relaxation of polymer chains or swelling (anomalous transport mechanism). Our results suggest that DEX-loaded CS/HA beads, crosslinked in TPP coagulation solution at pH = 9.0, led to a decrease in the DEX release rate and prolonged the release period. Thus, this composition might have prospective as a functional material for bone and cartilage tissue engineering.
The objective of the study was to estimate the contribution of ultra-processed foods to total caloric intake and investigate whether it differs according to socioeconomic position. We analyzed ...baseline data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil 2008-2010; N = 14.378) and data on dietary intake using a food frequency questionnaire, assigning it into three categories: unprocessed or minimally processed foods and processed culinary ingredients, processed foods, and ultra-processed foods. We measured the associations between socioeconomic position (education, per capita household income, and occupational social class) and the percentage of caloric contribution of ultra-processed foods, using generalized linear regression models adjusted for age and sex. Unprocessed or minimally processed foods and processed culinary ingredients contributed to 65.7% of the total caloric intake, followed by ultra-processed foods (22.7%). After adjustments, the percentage of caloric contribution of ultra-processed foods was 20% lower among participants with incomplete elementary school when compared to postgraduates. Compared to individuals from upper income classes, the caloric contribution of ultra-processed foods was 10%, 15% and 20% lower among the ones from the three lowest income, respectively. The caloric contribution of ultra-processed foods was also 7%, 12%, 12%, and 17% lower among participants in the lowest occupational social class compared to those from high social classes. Results suggest that the caloric contribution of ultra-processed foods is higher among individuals from high socioeconomic positions with a dose-response relationship for the associations.
ABSTRACT Purpose To develop a model of induction of type-2 diabetes (DM2) by combining low doses of streptozotocin (STZ) and a cafeteria diet. Methods Forty male Wistar rats (200 g) were allocated ...into four groups: control (non-diabetic, n = 10); STZ 30 mg/kg (diabetic, n = 10); STZ 35 mg/kg (diabetic,n = 10); and STZ 40 mg/kg (diabetic, n = 10). DM2 was induced with a single intraperitoneal injection of STZ after four weeks of cafeteria diet in the three diabetic groups. All animals were evaluated as for anthropometric, and biochemical analyses, as well as liver, kidney and pancreas histological analyses. Results Lower weight gain, higher water intake, higher Lee index, hyperglycemia and modified total protein, urea, alpha-amylase, as well as insulin resistance, hepatic steatosis, pancreas, and kidney injury were observed in animals treated with 35 and 40 mg/kg of STZ. Conclusions The results show that the experimental model using cafeteria diet associated with 35 mg/kg of STZ is a low-cost model and efficient in order to develop DM2, confirmed by the presence of polydipsia, hyperglycemia, altered biochemical tests, insulin resistance and damages to the liver, pancreas and kidney, which is similar to the disease found in humans.
Lower respiratory tract infections (LRIs) are a significant cause of disability-adjusted life-years (DALYs) across all age groups, especially in children under 9 years of age, and adults over 75. The ...main causative agents are viruses, such as influenza and respiratory syncytial virus (RSV). Viral LRIs in adults have historically received less attention. This study investigated the incidence of RSV and influenza in adult patients admitted to a referral hospital, as well as the clinical profile of these infections. Molecular testing was conducted on nasopharyngeal samples taken from a respiratory surveillance cohort comprising adult (15-59 years) and elderly (60+ years) hospitalized patients who tested negative for SARS-CoV-2, to determine the prevalence for influenza and RSV. Influenza was found to be less frequent among the elderly. The main symptoms of RSV infections were cough, fever, dyspnea, malaise, and respiratory distress, while headache, nasal congestion, a sore throat, and myalgia were most frequent in influenza. Elderly patients with RSV were not found to have more severe illness than adults under age 60, underscoring the importance of providing the same care to adults with this viral infection.
This work aimed to prepare chitosan/clay microspheres, by the precipitation method, for use in drug carrier systems. The influence of the process parameters, particularly two airflows of the drag ...system (2.5 and 10 L·min
) on the microspheres physical dimensions and properties, such as microstructure, degree of swelling and porosity were evaluated. The samples were characterized by optical microscopy (OM), scanning electron microscopy (SEM) and X-ray diffraction (XRD). Water absorption and porosity tests were also performed. The results showed that the process parameters affected the size of the microspheres. The diameter, volume and surface area of the chitosan/clay microspheres decreased when they were prepared with the higher airflow of the drag system. The microspheres presented a porous microstructure, being the pore size, percentage of porosity and degree of swelling affected not only by the process parameters but also by the type of clay. Hybrids (chitosan/clay) with intercalated morphology were obtained and the hybrid prepared with montmorillonite clay at higher airflows of the drag system presented the greatest interlayer spacing and a more disordered morphology. Thus, it is certain that the chitosan/clay nanocomposite microspheres prepared with montmorillonite (CL clay) at higher airflows of the drag system can have good drug-controlled release properties.
Neoadjuvant chemotherapy (NACT) can change invasive breast carcinomas (IBC) and influence the patients' overall survival time (OS). We aimed to identify IBC changes after NACT and their association ...with OS.
IBC data in pre- and post-NACT samples of 86 patients were evaluated and associated with OS.
Post-NACT tumors changed nuclear pleomorphism score (p=0.025); mitotic count (p=0.002); % of tumor-infiltrating inflammatory cells (p=0.016); presence of in situ carcinoma (p=0.001) and lymphovascular invasion (LVI; p=0.002); expression of estrogen (p=0.003), progesterone receptors (PR; p=0.019), and Ki67 (p=0.003). Immunohistochemical (IHC) profile changed in 26 tumors (30.2%, p=0.050). Higher risk of death was significatively associated with initial tumor histological grade III (hazard ratio HR, 2.94), high nuclear pleomorphism (HR, 2.53), high Ki67 index (HR, 2.47), post-NACT presence of LVI (HR, 1.90), luminal B-like profile (HR, 2.58), pre- (HR, 2.26) and post-NACT intermediate mitotic count (HR, 2.12), pre- (HR, 4.45) and post-NACT triple-negative IHC profile (HR, 4.52). On the other hand, lower risk of death was significative associated with pre- (HR, 0.35) and post-NACT (HR, 0.39) estrogen receptor-positive, and pre- (HR, 0.37) and post-NACT (HR, 0.57) PR-positive. Changes in IHC profile were associated with longer OS (p=0.050). In multivariate analysis, pre-NACT grade III tumors and pre-NACT and post-NACT triple negative IHC profile proved to be independent factors for shorter OS.
NACT can change tumor characteristics and biomarkers and impact on OS; therefore, they should be reassessed on residual samples to improve therapeutic decisions.
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