Dextran-curcumin nanoparticles as a methotrexate delivery vehicle: A step forward in breast cancer combination therapy

With the aim to effectively deliver methotrexate (MTX) to breast cancer cells, we designed a nanocarrier system (DC) derived from the self-assembly of a dextran-curcumin conjugate prepared via enzyme chemistry with immobilized laccase acting as a solid biocatalyst. Nanoparticles consisted of homogeneously dispersed nanospheres with a mean diameter of 290 nm, as characterized by combined transmission electron microscopy and dynamic light scattering investigations. DC was able to control the MTX release overtime (t1/2 value of 310 min), with cell internalization studies proving its presence inside MCF-7 cytoplasm. Finally, improved MTX efficacy was obtained in viability assays, and attributed to the synergy of curcumin moieties and loaded MTX as underlined by a combination index (CI) < 1

Chemical and biological investigations of Syzygium aromaticum L. essential oil from Benin

The essential oil obtained by hydrodistillation from seeds of Syzygium aromaticum (Myrtaceae) growing in Benin was analyzed by gas chromatography (GC) and gas chromatography-mass spectrometry (GC/MS). Twenty-one components, which represented 99.4% of the total constituents of the oil were identified. The essential oil is rich in hydrocarbons monoterpenic. The major constituents found were eugenol (60.4%), trans-&#946;-caryophyllene (24.0%). The oil extract revealed an important antiradical activity and a high antimicrobial activity.Keywords: Antimicrobial activity, antiradical activity, essential oil, eugenol, trans-&#946;-caryophyllene, Syzygium aromaticu

An Anti-Glitch in a Magnetar

Magnetars are neutron stars showing dramatic X-ray and soft $\gamma$-ray outbursting behaviour that is thought to be powered by intense internal magnetic fields. Like conventional young neutron stars in the form of radio pulsars, magnetars exhibit "glitches" during which angular momentum is believed to be transferred between the solid outer crust and the superfluid component of the inner crust. Hitherto, the several hundred observed glitches in radio pulsars and magnetars have involved a sudden spin-up of the star, due presumably to the interior superfluid rotating faster than the crust. Here we report on X-ray timing observations of the magnetar 1E 2259+586 which we show exhibited a clear "anti-glitch" -- a sudden spin down. We show that this event, like some previous magnetar spin-up glitches, was accompanied by multiple X-ray radiative changes and a significant spin-down rate change. This event, if of origin internal to the star, is unpredicted in models of neutron star spin-down and is suggestive of differential rotation in the neutron star, further supporting the need for a rethinking of glitch theory for all neutron stars

Onecut-dependent Nkx6.2 transcription factor expression is required for proper formation and activity of spinal locomotor circuits.

In the developing spinal cord, Onecut transcription factors control the diversification of motor neurons into distinct neuronal subsets by ensuring the maintenance of Isl1 expression during differentiation. However, other genes downstream of the Onecut proteins and involved in motor neuron diversification have remained unidentified. In the present study, we generated conditional mutant embryos carrying specific inactivation of Onecut genes in the developing motor neurons, performed RNA-sequencing to identify factors downstream of Onecut proteins in this neuron population, and employed additional transgenic mouse models to assess the role of one specific Onecut-downstream target, the transcription factor Nkx6.2. Nkx6.2 expression was up-regulated in Onecut-deficient motor neurons, but strongly downregulated in Onecut-deficient V2a interneurons, indicating an opposite regulation of Nkx6.2 by Onecut factors in distinct spinal neuron populations. Nkx6.2-null embryos, neonates and adult mice exhibited alterations of locomotor pattern and spinal locomotor network activity, likely resulting from defective survival of a subset of limb-innervating motor neurons and abnormal migration of V2a interneurons. Taken together, our results indicate that Nkx6.2 regulates the development of spinal neuronal populations and the formation of the spinal locomotor circuits downstream of the Onecut transcription factors

Combined effects of time spent in physical activity, sedentary behaviors and sleep on obesity and cardio-metabolic health markers: a novel compositional data analysis approach

<div><p>The associations between time spent in sleep, sedentary behaviors (SB) and physical activity with health are usually studied without taking into account that time is finite during the day, so time spent in each of these behaviors are codependent. Therefore, little is known about the combined effect of time spent in sleep, SB and physical activity, that together constitute a composite whole, on obesity and cardio-metabolic health markers. Cross-sectional analysis of NHANES 2005–6 cycle on N = 1937 adults, was undertaken using a compositional analysis paradigm, which accounts for this intrinsic codependence. Time spent in SB, light intensity (LIPA) and moderate to vigorous activity (MVPA) was determined from accelerometry and combined with self-reported sleep time to obtain the 24 hour time budget composition. The distribution of time spent in sleep, SB, LIPA and MVPA is significantly associated with BMI, waist circumference, triglycerides, plasma glucose, plasma insulin (all p<0.001), and systolic (p<0.001) and diastolic blood pressure (p<0.003), but not HDL or LDL. Within the composition, the strongest positive effect is found for the proportion of time spent in MVPA. Strikingly, the effects of MVPA replacing another behavior and of MVPA being displaced by another behavior are asymmetric. For example, re-allocating 10 minutes of SB to MVPA was associated with a lower waist circumference by 0.001% but if 10 minutes of MVPA is displaced by SB this was associated with a 0.84% higher waist circumference. The proportion of time spent in LIPA and SB were detrimentally associated with obesity and cardiovascular disease markers, but the association with SB was stronger. For diabetes risk markers, replacing SB with LIPA was associated with more favorable outcomes. Time spent in MVPA is an important target for intervention and preventing transfer of time from LIPA to SB might lessen the negative effects of physical inactivity.</p></div

The IgA nephropathy Biobank. An important starting point for the genetic dissection of a complex trait

BACKGROUND: IgA nephropathy (IgAN) or Berger's disease, is the most common glomerulonephritis in the world diagnosed in renal biopsied patients. The involvement of genetic factors in the pathogenesis of the IgAN is evidenced by ethnic and geographic variations in prevalence, familial clustering in isolated populations, familial aggregation and by the identification of a genetic linkage to locus IGAN1 mapped on 6q22–23. This study seems to imply a single major locus, but the hypothesis of multiple interacting loci or genetic heterogeneity cannot be ruled out. The organization of a multi-centre Biobank for the collection of biological samples and clinical data from IgAN patients and relatives is an important starting point for the identification of the disease susceptibility genes. DESCRIPTION: The IgAN Consortium organized a Biobank, recruiting IgAN patients and relatives following a common protocol. A website was constructed to allow scientific information to be shared between partners and to divulge obtained data (URL: ). The electronic database, the core of the website includes data concerning the subjects enrolled. A search page gives open access to the database and allows groups of patients to be selected according to their clinical characteristics. DNA samples of IgAN patients and relatives belonging to 72 multiplex extended pedigrees were collected. Moreover, 159 trios (sons/daughters affected and healthy parents), 1068 patients with biopsy-proven IgAN and 1040 healthy subjects were included in the IgAN Consortium Biobank. Some valuable and statistically productive genetic studies have been launched within the 5(th )Framework Programme 1998–2002 of the European project No. QLG1-2000-00464 and preliminary data have been published in "Technology Marketplace" website: . CONCLUSION: The first world IgAN Biobank with a readily accessible database has been constituted. The knowledge gained from the study of Mendelian diseases has shown that the genetic dissection of a complex trait is more powerful when combined linkage-based, association-based, and sequence-based approaches are performed. This Biobank continuously expanded contains a sample size of adequately matched IgAN patients and healthy subjects, extended multiplex pedigrees, parent-child trios, thus permitting the combined genetic approaches with collaborative studies

Subclinical liver fibrosis in patients with idiopathic 1 pulmonary fibrosis.

Background - Data on the presence of subclinical fibrosis across multiple organs in patients with idiopathic lung fibrosis (IPF) are lacking. Our study aimed at investigating through hepatic transient elastography (HTE) the prevalence and clinical impact of subclinical liver fibrosis in a cohort of patients with IPF. Methods - Patients referred to the Centre for Rare Lung Disease of the University Hospital of Modena (Italy) from March 2012 to February 2013with established diagnosis of IPF and without a documented history of liver diseases were consecutively enrolled and underwent HTE. Based on hepatic stiffness status as assessed through METAVIR score patients were categorized as \u201c with liver fibrosis \u201d (corresponding to a METAVIR score of F1-F4) and \u201c without liver fibrosis\u201d (METAVIR F0). Potential predictors of liver fibrosis were investigated through logistic regression model among clinical and serological variables. The overall survival (OS) was assessed according to liver fibrosis and multivariate Cox regression analysis was used to identify independent predictors. Results - In 13 out of 37 patients (35%) with IPF a certain degree of liver fibrosis was documented.No correlation was found between liver stiffness and clinical-functional parameters. OS was lower in patients \u2018 with liver fibrosis\u2019 than in patients \u2018 without liver fibrosis\u2019 (median months 33[23-55] vs. 63[26-94], p=0.038). Patients \u2018 with liver fibrosis\u2019 presented a higher risk of death at seven years as compared to patients \u2018without liver fibrosis\u2019 (HR=2.6, 95%CI[1.003\u20136.7],p= 0.049). Higher level of AST to platelet ratio Index (APRI)was an independent predictor of survival (HR=4.52 95%CI[1.3\u201315.6], p=0.02). Conclusions - In our cohort, more than one third of IPF patients had concomitant subclinical liver fibrosis that negatively affected OS. These preliminary claims further investigation aimed at clarifying the mechanisms beyond multiorgan fibrosis and its clinical implication in patients with IPF

Interpreting and acting upon home blood pressure readings: A qualitative study

This article is made available through the Brunel Open Access Publishing Fund. Copyright @ 2013 Vasileiou et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Recent guidelines recognize the importance of home blood pressure monitoring (HBPM) as an adjunct to clinical measurements. We explored how people who have purchased and use a home blood pressure (BP) monitor make sense of, and act upon, readings and how they communicate with their doctor about the practice of home monitoring. Methods: A qualitative study was designed and participants were purposively recruited from several areas in England, UK. Semi-structured in-depth interviews were conducted with 18 users of home BP monitors. The transcribed data were thematically analysed. Results: Interpretation of home BP readings is complex, and is often characterised by uncertainty. People seek to assess value normality using ‘rules of thumb’, and often aim to identify the potential causes of the readings. This is done by drawing on lay models of BP function and by contextualising the readings to personal circumstances. Based on the perceived causes of the problematic readings, actions are initiated, mostly relating to changes in daily routines. Contacting the doctor was more likely when the problematic readings persisted and could not be easily explained, or when participants did not succeed in regulating their BP through their other interventions. Most users had notified their doctor of the practice of home monitoring, but medical involvement varied, with some participants reporting disinterest or reservations by doctors. Conclusions: Involvement from doctors can help people overcome difficulties and resolve uncertainties around the interpretation of home readings, and ensure that the rules of thumb are appropriate. Home monitoring can be used to strengthen the patient-clinician relationship

Diagnostic and prognostic value of Bcl-2 in uterine leiomyosarcoma

Background Uterine leiomyosarcoma (uLMS) may show loss of expression of B-cell lymphoma-2 (Bcl-2) protein. It has been suggested that Bcl-2 loss may both be a diagnostic marker and an unfavorable prognostic marker in uLMS. Objective To define the diagnostic and prognostic value of Bcl-2 loss in uLMS through a systematic review and meta-analysis. Methods Electronic databases were searched from their inception to May 2020 for all studies assessing the diagnostic and prognostic value of Bcl-2 loss of immunohistochemical expression in uLMS. Data were extracted to calculate odds ratio (OR) for the association of Bcl-2 with uLMS vs leiomyoma variants and smooth-muscle tumors of uncertain malignant potential (STUMP), and hazard ratio (HR) for overall survival; a p value &lt; 0.05 was considered significant. Results Eight studies with 388 patients were included. Loss of Bcl-2 expression in uLMS was not significantly associated with a diagnosis of uLMS vs leiomyoma variants and STUMP (OR = 2.981; p = 0.48). Bcl-2 loss was significantly associated with shorter overall survival in uLMS (HR = 3.722; p = 0.006). High statistical heterogeneity was observed in both analyses. Conclusion Loss of Bcl-2 expression appears as a significant prognostic but not diagnostic marker in uLMS. The high heterogeneity observed highlights the need for further research and larger studies