Doxorubicin Hydrochloride-Loaded Nonionic Surfactant Vesicles to Treat Metastatic and Non-Metastatic Breast Cancer

Doxorubicin hydrochloride (DOX) is currently used to treat orthotropic and metastatic breast cancer. Because of its side effects, the use of DOX in cancer patients is sometimes limited; for this reason, several scientists tried designing drug delivery systems which can improve drug therapeutic efficacy and decrease its side effects. In this study, we designed, prepared, and physiochemically characterized nonionic surfactant vesicles (NSVs) which are obtained by self-assembling different combinations of hydrophilic (Tween 20) and hydrophobic (Span 20) surfactants, with cholesterol. DOX was loaded in NSVs using a passive and pH gradient remote loading procedure, which increased drug loading from ∼1 to ∼45%. NSVs were analyzed in terms of size, shape, size distribution, zeta potential, long-term stability, entrapment efficiency, and release kinetics, and nanocarriers having the best physiochemical parameters were selected for further in vitro tests. NSVs with and without DOX were stable and showed a sustained drug release up to 72 h. In vitro studies, with MCF-7 and MDA MB 468 cells, demonstrated that NSVs, containing Span 20, were better internalized in MCF-7 and MDA MB 468 cells than NSVs with Tween 20. NSVs increased the anticancer effect of DOX in MCF-7 and MDA MB 468 cells, and this effect is time and dose dependent. In vitro studies using metastatic and nonmetastatic breast cancer cells also demonstrated that NSVs, containing Span 20, had higher cytotoxicity than NSVs with Tween 20. The resulting data suggested that DOX-loaded NSVs could be a promising nanocarrier for the potential treatment of metastatic breast cancer

Tinnitus and equilibrium disorders in COVID-19 patients: preliminary results

Purpose: Tinnitus and equilibrium disorders such as dizziness and vertigo have been reported by patients with COVID-19; however, they have been rarely investigated. The aim of this study was to study the prevalence of subjective tinnitus and dizziness in a sample of COVID-19 patients using an online 10-item close-ended questionnaire. Methods: A multicentric study that included 15 Italian hospitals in different regions was conducted using an online 10-item close-ended questionnaire developed to identify the presence of tinnitus and balance disorders in patients with COVID-19 between May 5 and June 10, 2020. The questionnaire was administered to 185 patients in a period of > 30 – < 60 days after diagnosis of COVID-19; responses were recorded in an online Excel spreadsheet. The questionnaire was composed of three sections: (1) demographic information; (2) presence and characteristics of tinnitus and dizziness after COVID-19 diagnosis; (3) possible association with migraine. Results: Thirty-four patients (18.4%) reported equilibrium disorders after COVID-19 diagnosis. Of these, 32 patients reported dizziness (94.1%) and 2 (5.9%) reported acute vertigo attacks. Forty-three patients (23.2%) reported tinnitus; 14 (7.6%) reported both tinnitus and equilibrium disorders. Conclusion: This study suggests that the presence of subjective otoneurological symptoms such as tinnitus and balance disorders can affect COVID-19 patients; further studies are necessary to investigate the prevalence and pathophysiological mechanisms underlying these subjective symptoms in COVID-19 patients

Early life stress regulates cardiac development through an IL4-glucocorticoid signaling balance

Stressful experiences early in life can increase the risk of cardiovascular diseases. However, it remains largely unknown how stress influences susceptibility to the disease onset. Here, we show that exposure to brain-processed stress disrupts myocardial growth by reducing cardiomyocyte mitotic activity. Activation of the glucocorticoid receptor (GR), the primary stress response pathway, reduces cardiomyocyte numbers, disrupts trabecular formation, and leads to contractile dysfunction of the developing myocardium. However, a physiological level of GR signaling is required to prevent cardiomyocyte hyperproliferation. Mechanistically, we identify an antagonistic interaction between the GR and the cytokine interleukin-4 (IL-4) as a key player in cardiac development. IL-4 signals transcription of key regulators of cell-cycle progression in cardiomyocytes via signal transducer and activator of transcription 3 (Stat3). GR, on the contrary, inhibits this signaling system. Thus, our findings uncover an interplay between stress and immune signaling pathways critical to orchestrating physiological growth of the heart

Exposure to multiple childhood social risk factors and adult body mass index trajectories from ages 20 to 64 years

Background While childhood social risk factors appear to be associated with adult obesity, it is unclear whether exposure to multiple childhood social risk factors is associated with accelerated weight gain during adulthood. Methods We used the Medical Research Council National Survey of Health and Development, a British population-based birth cohort study of participants born in 1946, height and weight were measured by nurses at ages 36, 43, 53 and 60–64 and self-reported at 20 and 26 years. The 9 childhood socioeconomic risk factors and 8 binary childhood psychosocial risk factors were measured, with 13 prospectively measured at age 4 years (or at 7 or 11 years if missing) and 3 were recalled when participants were age 43. Multilevel modelling was used to examine the association between the number of childhood social risk factors and changes in body mass index (BMI) with age. Results Increasing exposure to a higher number of childhood socioeconomic risk factors was associated with higher mean BMI across adulthood for both sexes and with a faster increase in BMI from 20 to 64 years, among women but not men. Associations remained after adjustment for adult social class. There was no evidence of an association between exposure to childhood psychosocial risk factors and mean BMI in either sex at any age. Conclusions Strategies for the prevention and management of weight gain across adulthood may need to tailor interventions in consideration of past exposure to multiple socioeconomic disadvantages experienced during childhood

PNPLA3 148M Carriers with Inflammatory Bowel Diseases Have Higher Susceptibility to Hepatic Steatosis and Higher Liver Enzymes

BACKGROUND: Inflammatory bowel diseases (IBD) are characterized by chronic relapsing inflammation of the gastrointestinal tract and encompass Crohn's disease and ulcerative colitis. IBD are often associated with extraintestinal manifestations affecting multiple organs including the liver. Increased levels of serum aminotransferases, possibly related to nonalcoholic fatty liver disease, constitute one of the most frequently described IBD-related liver diseases. The PNPLA3 I148M substitution is a major common genetic determinant of hepatic fat content and progression to chronic liver disease. The aim of this study was to investigate whether carriers of PNPLA3 148M allele with IBD have higher risk of liver steatosis and increase in transaminases levels. METHODS: The PNPLA3 I148M (rs738409) genotype was performed by Taqman assays in 158 individuals from Southern Italy (namely, Catanzaro cohort) and in 207 individuals from Northern Italy (namely, Milan cohort) with a definite diagnosis of IBD. Demographic and clinical data and also alanine transaminase levels were collected for both cohorts. The Catanzaro cohort underwent liver evaluation by sonography and liver stiffness and controlled attenuation parameter measurements by transient elastography. RESULTS: Here, we show for the first time that carriers of the PNPLA3 148M allele with IBD have a greater risk of hepatic steatosis (odds ratio, 2.9, and confidence interval, 1.1-7.8), higher controlled attenuation parameter values (P = 0.029), and increased circulating alanine transaminase (P = 0.035) in the Catanzaro cohort. We further confirm the higher alanine transaminase levels in the Milan cohort (P < 0.001). CONCLUSIONS: Our results show that PNPLA3 148M carriers with IBD have higher susceptibility to hepatic steatosis and liver damage