Effect of dietary omega-3 fatty acids on castrate-resistant prostate cancer and tumor-associated macrophages.

BackgroundM2-like macrophages are associated with the pathogenesis of castrate-resistant prostate cancer (CRPC). We sought to determine if dietary omega-3 fatty acids (ω-3 FAs) delay the development and progression of CRPC and inhibit tumor-associated M2-like macrophages.MethodsMycCap cells were grown subcutaneously in immunocompetent FVB mice. Mice were castrated when tumors reached 300 mm2. To study effects of dietary ω-3 FAs on development of CRPC, ω-3 or ω-6 diets were started 2 days after castration and mice sacrificed after early regrowth of tumors. To study ω-3 FA effects on progression of CRPC, tumors were allowed to regrow after castration before starting the diets. M2 (CD206+) macrophages were isolated from allografts to examine ω-3 FA effects on macrophage function. Omega-3 fatty acid effects on androgen-deprived RAW264.7 M2 macrophages were studied by RT-qPCR and a migration/ invasion assay.ResultsThe ω-3 diet combined with castration lead to greater MycCap tumor regression (tumor volume reduction: 182.2 ± 33.6 mm3) than the ω-6 diet (tumor volume reduction: 148.3 ± 35.2; p = 0.003) and significantly delayed the time to CRPC (p = 0.006). Likewise, the ω-3 diet significantly delayed progression of established castrate-resistant MycCaP tumors (p = 0.003). The ω-3 diet (as compared to the ω-6 diet) significantly reduced tumor-associated M2-like macrophage expression of CSF-1R in the CRPC development model, and matrix metallopeptidase-9 (MMP-9) and vascular endothelial growth factor (VEGF) in the CRPC progression model. Migration of androgen-depleted RAW264.7 M2 macrophages towards MycCaP cells was reversed by addition of docosahexaenoic acid (ω-3).ConclusionsDietary omega-3 FAs (as compared to omega-6 FAs) decreased the development and progression of CRPC in an immunocompetent mouse model, and had inhibitory effects on M2-like macrophage function. Clinical trials are warranted evaluating if a fish oil-based diet can delay the time to castration resistance in men on androgen deprivation therapy, whereas further preclinical studies are warranted evaluating fish oil for more advanced CRPC

An Outbreak of Hepatic Veno-Occlusive Disease in Western Afghanistan Associated with Exposure to Wheat Flour Contaminated with Pyrrolizidine Alkaloids

Pyrrolizidine alakloids (PAs) are known to cause hepatic veno-occlusive disease (VOD). Outbreaks have occurred in Western Afghanistan since 1974, the latest in February 2008. We conducted an outbreak investigation using a case-control design. Sixty-seven cases of VOD were compared with 199 community controls. Consumption of bread was strongly associated with disease (adjusted odds ratio: 35.8 [95%CI: 7.6–168.2]). Toxic doses of PA were found in plant extracts and in samples of wheat flour taken from the study area. Compared to wheat flour there was 1000 times less PA in milk and whey and in water samples the PA content was zero. Although direct analysis was not possible, contaminated wheat flour used to make bread was the likely source of PA causing the outbreak. Eating a more varied diet including meat and fruit may be protective. Prevention and control measures will rely on community awareness and agricultural interventions to ensure safety of the food supply

Comparing Effect of Safranal and Diazepam in Reducing Preoperative Anxiety and Improving Vital Symptoms

Aim: Preoperative anxiety is an unpleasant manner created by fear of surgery. The aim of the present study was to compare the effects of diazepam pill with Safranal in reducing preoperative anxiety and improving vital symptoms. Material and Methods: In this double blind randomized clinical trial, 54 patients who were candidates of urology surgery (varicocele) in 15th Khordad Hospital, Gonabad, Iran, were selected by purposive sampling method, using a randomized numbers table; they were divided into intervention (n=29) and control group (n=25). The patients in intervention group received 15mg Safranal and the patients in control group received 5mg oral diazepam 3 hours before surgery. The State-Trait Anxiety Inventory (STAI) questionnaire was completed by the patients prior to the intervention and just at the entrance to the surgery room, and the vital symptoms of the patient were evaluated. The data were analyzed by SPSS 11.5 software, using of Chi-square and independent sample t-test. Findings: After intervention, the trait anxiety in the Safranal group was significantly lower than diazepam group (p=0.007) and before the intervention (p=0.002). Also, diastolic blood pressure decreased significantly in the Safranal group compared with the diazepam group (p=0.049). Conclusion: Saffranal consumption before surgery is more effective than diazepam consumption in reducing the trait anxiety, but it does not affect state anxiety. Also, compared to diazepam, Saffranal consumption leads to a more reduction in diastolic blood pressure, while it does not affect systolic blood pressure and heart rate

Corneal regeneration using adipose-derived mesenchymal stem cells

Producción CientíficaAdipose-derived stem cells are a subtype of mesenchymal stem cell that offers the important advantage of being easily obtained (in an autologous manner) from low invasive procedures, rendering a high number of multipotent stem cells with the potential to differentiate into several cellular lineages, to show immunomodulatory properties, and to promote tissue regeneration by a paracrine action through the secretion of extracellular vesicles containing trophic factors. This secretome is currently being investigated as a potential source for a cell-free based regenerative therapy for human tissues, which would significantly reduce the involved costs, risks and law regulations, allowing for a broader application in real clinical practice. In the current article, we will review the existing preclinical and human clinical evidence regarding the use of such adipose-derived mesenchymal stem cells for the regeneration of the three main layers of the human cornea: the epithelium (derived from the surface ectoderm), the stroma (derived from the neural crest mesenchyme), and the endothelium (derived from the neural crest cells)

CHIME/FRB Discovery of 25 Repeating Fast Radio Burst Sources

We present the discovery of 25 new repeating fast radio burst (FRB) sources found among CHIME/FRB events detected between 2019 September 30 and 2021 May 1. The sources were found using a new clustering algorithm that looks for multiple events co-located on the sky having similar dispersion measures (DMs). The new repeaters have DMs ranging from $\sim$220 pc cm$^{-3}$ to $\sim$1700 pc cm$^{-3}$, and include sources having exhibited as few as two bursts to as many as twelve. We report a statistically significant difference in both the DM and extragalactic DM (eDM) distributions between repeating and apparently nonrepeating sources, with repeaters having lower mean DM and eDM, and we discuss the implications. We find no clear bimodality between the repetition rates of repeaters and upper limits on repetition from apparently nonrepeating sources after correcting for sensitivity and exposure effects, although some active repeating sources stand out as anomalous. We measure the repeater fraction and find that it tends to an equilibrium of $2.6_{-2.6}^{+2.9}$% over our exposure thus far. We also report on 14 more sources which are promising repeating FRB candidates and which merit follow-up observations for confirmation.Comment: Submitted to ApJ. Comments are welcome and follow-up observations are encouraged

Sub-second periodicity in a fast radio burst

Fast radio bursts (FRBs) are millisecond-duration flashes of radio waves that are visible at distances of billions of light-years. The nature of their progenitors and their emission mechanism remain open astrophysical questions. Here we report the detection of the multi-component FRB 20191221A and the identification of a periodic separation of 216.8(1) ms between its components with a significance of 6.5 sigmas. The long (~3 s) duration and nine or more components forming the pulse profile make this source an outlier in the FRB population. Such short periodicity provides strong evidence for a neutron-star origin of the event. Moreover, our detection favours emission arising from the neutron-star magnetosphere, as opposed to emission regions located further away from the star, as predicted by some models.Comment: Updated to conform to the accepted versio

The multiple faces of self-assembled lipidic systems

Lipids, the building blocks of cells, common to every living organisms, have the propensity to self-assemble into well-defined structures over short and long-range spatial scales. The driving forces have their roots mainly in the hydrophobic effect and electrostatic interactions. Membranes in lamellar phase are ubiquitous in cellular compartments and can phase-separate upon mixing lipids in different liquid-crystalline states. Hexagonal phases and especially cubic phases can be synthesized and observed in vivo as well. Membrane often closes up into a vesicle whose shape is determined by the interplay of curvature, area difference elasticity and line tension energies, and can adopt the form of a sphere, a tube, a prolate, a starfish and many more. Complexes made of lipids and polyelectrolytes or inorganic materials exhibit a rich diversity of structural morphologies due to additional interactions which become increasingly hard to track without the aid of suitable computer models. From the plasma membrane of archaebacteria to gene delivery, self-assembled lipidic systems have left their mark in cell biology and nanobiotechnology; however, the underlying physics is yet to be fully unraveled

The prevalence of obesity and the knowledge, attitude and practice of healthy lifestyle among the adult population in Kampung Banyuk, Kampung Kerto and Kampung Langup

Background Obesity has become a great public health concern and prevent!ive measures need to be done. Objective The objective of this research is to determine the prevalence ofobesity and their knowledge, attitude and practices (KAP) towards a healthy lifestyle among the residents in Kampung Banyok, Kampung Kerto and Kampung Langup. Methods A cross-sectional study was done among 126 randomly selected villagers aged 18 years and above from the three selected villages. They were interviewed based on a questionnaire and their body mass index (BMI) was calculated. Results It was found that more than half of the respondents are obese. Among the respondents, for the healthy lifestyle component, the level of good KAP is 69.2%, 46.8% and 60.3% respectively. As for obesity component, the level of good KAP is 60.3%, 54% and 54.8% respectively. Among the obese respondents, the level of knowledge and attitude on healthy lifestyle and obesity is better. Obese respondents have better obesity preventive practice while the non-obese respondents have better practice on healthy lifestyle. The only significant correlation noted was between knowledge and practice on obesity albeit a negative one. Conclusion The level of knowledge and attitude and practice on healthy lifestyle among the obese respondents are encouraged but more effort in the preventive practice ofobesity shou1d be done to reduce the prevalence.

Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis

Supported by F. Hoffmann–La Roche