Physiology and physical chemistry of bile acids

Bile acids (BAs) are facial amphiphiles synthesized in the body of all vertebrates. They undergo the enterohepatic circulation: they are produced in the liver, stored in the gallbladder, released in the intestine, taken into the bloodstream and lastly re-absorbed in the liver. During this pathway, BAs are modified in their molecular structure by the action of enzymes and bacteria. Such transformations allow them to acquire the chemical–physical properties needed for fulling several activities including metabolic regulation, antimicrobial functions and solubilization of lipids in digestion. The versatility of BAs in the physiological functions has inspired their use in many bioapplications, making them important tools for active molecule delivery, metabolic disease treatments and emulsification processes in food and drug industries. Moreover, moving over the borders of the biological field, BAs have been largely investigated as building blocks for the construction of supramolecular aggregates having peculiar structural, mechanical, chemical and optical properties. The review starts with a biological analysis of the BAs functions before progressively switching to a general overview of BAs in pharmacology and medicine applications. Lastly the focus moves to the BAs use in material science

An ultra-spatially resolved method to quali-quantitative monitor particulate matter in urban environment

Monitoring the amount and composition of airborne particulate matter (PM) in the urban environment is a crucial aspect to guarantee citizen health. To focus the action of stakeholders in limiting air pollution, fast and highly spatially resolved methods for monitoring PM are required. Recently, the trees’ capability in capturing PM inspired the development of several methods intended to use trees as biomonitors; this results in the potential of having an ultra-spatially resolved network of low-cost PM monitoring stations throughout cities, without the needing of on-site stations. Within this context, we propose a fast and reliable method to qualitatively and quantitatively characterize the PM present in urban air based on the analysis of tree leaves by scanning electron microscopy combined with X-ray spectroscopy (SEM/EDX). We have tested our method in the Real Bosco di Capodimonte urban park (Naples, Italy), by collecting leaves from Quercus ilex trees along transects parallel to the main wind directions. The coarse (PM10–2.5) and fine (PM2.5) amounts obtained per unit leaf area have been validated by weighting the PM washed from leaves belonging to the same sample sets. PM size distribution and elemental composition match appropriately with the known pollution sources in the sample sites (i.e., traffic and marine aerosol). The proposed methodology will then allow the use of the urban forest as an ultra-spatially resolved PM monitoring network, also supporting the work of urban green planners and stakeholders.5s

Whole-exome analysis in osteosarcoma to identify a personalized therapy

Osteosarcoma is the most common pediatric primary non-hematopoietic bone tumor. Survival of these young patients is related to the response to chemotherapy and development of metastases. Despite many advances in cancer research, chemotherapy regimens for osteosarcoma are still based on non-selective cytotoxic drugs. It is essential to investigate new specific molecular therapies for osteosarcoma to increase the survival rate of these patients. We performed exomic sequence analyses of 8 diagnostic biopsies of patients with conventional high grade osteosarcoma to advance our understanding of their genetic underpinnings and to correlate the genetic alteration with the clinical and pathological features of each patient to identify a personalized therapy. We identified 18,275 somatic variations in 8,247 genes and we found three mutated genes in 7/8 (87%) samples (KIF1B, NEB and KMT2C). KMT2C showed the highest number of variations; it is an important component of a histone H3 lysine 4 methyltransferase complex and it is one of the histone modifiers previously implicated in carcinogenesis, never studied in osteosarcoma. Moreover, we found a group of 15 genes that showed variations only in patients that did not respond to therapy and developed metastasis and some of these genes are involved in carcinogenesis and tumor progression in other tumors. These data could offer the opportunity to get a key molecular target to identify possible new strategies for early diagnosis and new therapeutic approaches for osteosarcoma and to provide a tailored treatment for each patient based on their genetic profile

Hemp (Cannabis sativa L.) flour: an active ingredient for the formulation of nutritious, flavorful and affordable foods.

Hemp (Cannabis sativa L.) flour is obtained as a byproduct of hemp oil processing. Considered so far a food waste, it represents a significant source of nutritionally relevant compounds. Actually, besides being high in fibres and micronutrients, hemp flour is characterized by a peculiar protein content, devoid of prolamins, which allows it to be tolerated by people who suffer from celiac disease or by those who are sensitive to gluten. Moreover, the lipid profile includes high and well-balanced omega-6 and omega-3 fatty acids and the calorie content is lower if compared to the more refined wheat flour. Significantly, hemp flour is high in polyphenolic compounds, which provide the product with a relevant anti-oxidant efficacy. Altogether, the chemical composition makes this flour a well balance ingredient having the potential to be used as an active component for the formulation of foods

Splenic Doppler Resistive Index Variation Mirrors Cardiac Responsiveness and Systemic Hemodynamics upon Fluid Challenge Resuscitation in Postoperative Mechanically Ventilated Patients

Objective. To test if splenic Doppler resistive index (SDRI) allows noninvasive monitoring of changes in stroke volume and regional splanchnic perfusion in response to fluid challenge. Design and Setting. Prospective observational study in cardiac intensive care unit. Patients. Fifty-three patients requiring mechanical ventilation and fluid challenge for hemodynamic optimization after cardiac surgery. Interventions. SDRI values were obtained before and after volume loading with 500 mL of normal saline over 20 min and compared with changes in systemic hemodynamics, determined invasively by pulmonary artery catheter, and arterial lactate concentration as expression of splanchnic perfusion. Changes in stroke volume >10% were considered representative of fluid responsiveness. Results. A <4% SDRI reduction excluded fluid responsiveness, with 100% sensitivity and 100% negative predictive value. A >9% SDRI reduction was a marker of fluid responsiveness with 100% specificity and 100% positive predictive value. A >4% SDRI reduction was always associated with an improvement of splanchnic perfusion mirrored by an increase in lactate clearance and a reduction in systemic vascular resistance, regardless of fluid responsiveness. Conclusions. This study shows that SDRI variations after fluid administration is an effective noninvasive tool to monitor systemic hemodynamics and splanchnic perfusion upon volume administration, irrespective of fluid responsiveness in mechanically ventilated patients after cardiac surgery

RGD_PLGA Nanoparticles with Docetaxel: A Route for Improving Drug Efficiency and Reducing Toxicity in Breast Cancer Treatment

Breast cancer is the leading cause of cancer-related death in women. Although many therapeutic approaches are available, systemic chemotherapy remains the primary choice, especially for triple-negative and advanced breast cancers. Unfortunately, systemic chemotherapy causes serious side effects and requires high doses to achieve an effective concentration in the tumor. Thus, the use of nanosystems for drug delivery may overcome these limitations. Herein, we formulated Poly (lactic-co-glycolic acid) nanoparticles (PLGA-NPs) containing Docetaxel, a fluorescent probe, and a magnetic resonance imaging (MRI) probe. The cyclic RGD tripeptide was linked to the PLGA surface to actively target αvβ3 integrins, which are overexpressed in breast cancer. PLGA-NPs were characterized using dynamic light scattering, fast field-cycling 1H-relaxometry, and 1H-nuclear magnetic resonance. Their therapeutic effects were assessed both in vitro in triple-negative and HER2+ breast cancer cells, and in vivo in murine models. In vivo MRI and inductively coupled plasma mass spectrometry of excised tumors revealed a stronger accumulation of PLGA-NPs in the RGD_PLGA group. Targeted PLGAs have improved therapeutic efficacy and strongly reduced cardiac side effects compared to free Docetaxel. In conclusion, RGD-PLGA is a promising system for breast cancer treatment, with positive outcome in terms of therapeutic efficiency and reduction in side effects