Repetition of FDG PET study in the same day after appropriate patient preparation revealed two new cancer localizations: a case report

A positron emission tomography scan with fluorodeoxyglucosecan be affected by several factors. Skeletal muscle activation andphysiological presence of radioactivity in urine frequently causedifficulties in images interpretation. We report a case of a patientwith a non-operable left lung cancer, who was scheduled forFDG PET examination for radiotherapy planning purposes. In thefirst scan performed in the morning both elevated muscular andurinary uptake were present. For this reason another examinationwas performed on the same day. A new dose of radiopharmaceutical was given five hours after the first FDG injection and the patient was instructed to drink a large quantity of water in themeantime. The second PET scan clearly revealed two new lesions not visible at the time of the first examination: a synchronous bladder cancer, previously not known, and a mediastinal metastasis of the primary lung cancer. This case emphasizes the importance of correct patient preparation and shows the possibility to repeat PET examination on the same day

Two bullets in the gun: combining immunotherapy with chemotherapy to defeat neuroblastoma by targeting adrenergic-mesenchymal plasticity

Neuroblastoma (NB) is a childhood tumor that originates in the peripheral sympathetic nervous system and is responsible for 15% of cancer-related deaths in the pediatric population. Despite intensive multimodal treatment, many patients with high-risk NB relapse and develop a therapy-resistant tumor. One of the phenomena related to therapeutic resistance is intratumor heterogeneity resulting from the adaptation of tumor cells in response to different selective environmental pressures. The transcriptional and epigenetic profiling of NB tissue has recently revealed the existence of two distinct cellular identities in the NB, termed adrenergic (ADRN) and mesenchymal (MES), which can spontaneously interconvert through epigenetic regulation. This phenomenon, known as tumor plasticity, has a major impact on cancer pathogenesis. The aim of this review is to describe the peculiarities of these two cell states, and how their plasticity affects the response to current therapeutic treatments, with special focus on the immunogenic potential of MES cells. Furthermore, we will discuss the opportunity to combine immunotherapy with chemotherapy to counteract NB phenotypic interconversion

Reprogramming of human keratinocytes into functional cardiomyocytes

Purpose. Induced pluripotent stem cells (iPS) can be generated by patients intro- ducing transcription factors that are highly expressed in embryonic stem (ES) cells into somatic cells. However, the various iPS cell lines are characterized by different properties such as differentiation efficiency and potential safety hazards. Among several readily available primary human somatic cell types, keratinocytes can be isolated easily from human skin or hair follicle, and therefore represent an attractive cell source for reprogramming. The aims of the present study were: 1. To assess the cardiomyogenic potential of human keratynocytes-derived iPS. 2. To increase the differentiation efficiency in order to obtain a homogeneous population of beating cardiomyocytes, also overcoming the limitation of embryonic body formation.Methods. Established iPS cell line obtained from human keratinocytes was cultured in monolayer and exposed sequentially to Ascorbic Acid, 5-Azacytidine, BMP4, ActivinA, VEGF up to 20 days. Differentiation was evaluated monitoring the expression of Nkx2.5, Gata4, sarcomeric α-actinin, α cardiac myosin heavy chain, cardiac T-troponin and Connexin43 and β-adrenoceptors as cardiac markers, by Western Blot, immunofluorescent and cytometric analyses. An ImageStream analysis for a simulta- neous quantitative and morphological evaluation was also performed.Results. During the differentiation induction, iPS became positive to all the analyzed cardiac markers. In particular, we observed a rapid and significant increase of Nkx2.5 and Gata4 expression (14.7±0.7% vs 43.2±2.1% Nkx2.5+ and 21.7±1.2 vs 65.9±3.6% Gata4+ in iPS and 15 days after the induction respectively, p<.005, analy- sis by ImageStream), with a significant nuclear translocation (nuclear+ cells:7.2±0.8% vs 18.8±2.1% of the Nkx2.5+ cells in iPS and 15 days after the induction respectively, p<.005, analysis by ImageStream). The differentiation process was accompanied by a modulation of β1- and β2-adrenoceptors expression. Foci of spontaneous contraction were observed after only 5 days from the induction and after 15 days the beating cells represented about the 60-90% of the entire population. Moreover, differentiated cardio- myocytes responded to adrenergic stimulation by increasing the contraction rate. Conclusion. iPS obtained from hKeratinocytes efficiently differentiate into cardi- omyocytes giving rise to a homogenous population with cardiac-specific molecular and functional properties

Role of nicotine during diabetic macular edema development

Diabetic macular edema (DME) represents the major cause of visual loss in diabetes patients. It is characterized by retinal thickening in the macular area due to breakdown of the blood-retinal barrier (BRB) [1]. By altering blood vessels supplying retina, hyperglycemia triggers tissue hypoxia. The primary response to latter is mediated by hypoxia-inducible factors (HIFs) which in turn promote vascular endothelial growth factor (VEGF) expression. The most important psychoactive compound in cigarette smoke, nicotine (NT), binds nicotinic cholinergic receptors (nAchRs) which are widely distributed in several human tissues, including retinal pigmented epithelium (RPE) [2]. Until now, little is known about risk factors linked to cigarette smoke inducing DME development. In the present study, we have evaluated NT effect in an in vitro model of outer BRB following exposure to hyperglycemic/hypoxic insult mimicking DME microenvironment. Our results have suggested that NT deeply impacts on outer BRB integrity by increasing its permeability. To investigate the molecular mechanisms involved in negative effect of this compound, we have analyzed HIF/VEGF system in cells exposed to hyperglycemic/hypoxic damage. NT treatment induced upregulation of HIF-1α/HIF-2α, VEGF mediated through activation of MAPK/ERK1/2 pathway. In conclusion, all this data have suggested a unfavorable role of this psychoactive agent in smokers DME affected

Air Pollution: Role of Extracellular Vesicles-Derived Non-Coding RNAs in Environmental Stress Response

Air pollution has increased over the years, causing a negative impact on society due to the many health-related problems it can contribute to. Although the type and extent of air pollutants are known, the molecular mechanisms underlying the induction of negative effects on the human body remain unclear. Emerging evidence suggests the crucial involvement of different molecular mediators in inflammation and oxidative stress in air pollution-induced disorders. Among these, non-coding RNAs (ncRNAs) carried by extracellular vesicles (EVs) may play an essential role in gene regulation of the cell stress response in pollutant-induced multiorgan disorders. This review highlights EV-transported ncRNAs’ roles in physiological and pathological conditions, such as the development of cancer and respiratory, neurodegenerative, and cardiovascular diseases following exposure to various environmental stressors

Resolvin D1 Modulates the Intracellular VEGF-Related miRNAs of Retinal Photoreceptors Challenged With High Glucose

Stimulation of retinal photoreceptors with elevated glucose concentration (30 mM) for 96 h, served as diabetic retinopathy in vitro model to study Resolvin D1 (50 nM) effects on neovascularization. VEGF and anti-angiogenic miR-20a-3p, miR-20a-5p, miR-106a- 5p, and miR-20b expression was assessed either in photoreceptors exposed to HG or in exosomes released by those cells. High glucose increased VEGF levels and concurrently decreased anti-angiogenic miRNAs content in photoreceptors and exosomes. RvD1 reverted the effects of glucose damage in photoreceptors and exosomal pro-angiogenic potential, tested with the HUVEC angiogenesis assay. By activating FPR2 receptor, RvD1 modulated both the expression of anti-angiogenic miRNA, which decrease VEGF, and the pro-angiogenic potential of exosomes released by primary retinal cells. HUVEC transfection with miR-20a-3p, miR-20a-5p, miR-106a-5p, and miR-20b antagomirs, followed by exposure to exosomes from photoreceptors, confirmed the VEGF-related miRNAs mechanism and the anti-angiogenic effects of RvD1

Extra virgin olive oil reduces gut permeability and metabolic endotoxemia in diabetic patients

Background: Extra virgin olive oil (EVOO) improves post-prandial glycemia, but the underlying mechanism has not been fully elucidated. We tested the hypothesis that EVOO improves post-prandial glycemia by reducing gut permeability-derived low-grade endotoxemia. Methods: Serum levels of lipopolysaccharides (LPS), zonulin, a marker of gut permeability, glucose, insulin and glucagon-like peptide 1 (GLP1) were measured in 20 patients with impaired fasting glucose (IFG) and 20 healthy subjects (HS) matched for sex and age. The same variables were measured in IFG patients (n = 20) and HS (n = 20) before and after a Mediterranean diet with 10 g EVOO added or not (n = 20) or in IFG patients (n = 20) before and after intake of 40 g chocolate with EVOO added or not. Results: Compared to HS, IFG had higher levels of LPS and zonulin. In HS, meal intake was associated with a significant increase of blood glucose, insulin, and GLP1 with no changes of blood LPS and zonulin. Two hours after a meal intake containing EVOO, IFG patients showed a less significant increase of blood glucose, a more marked increase of blood insulin and GLP1 and a significant reduction of LPS and zonulin compared to IFG patients not given EVOO. Correlation analysis showed that LPS directly correlated with blood glucose and zonulin and inversely with blood insulin. Similar findings were detected in IFG patients given a chocolate added or without EVOO. Conclusion: Addition of EVOO to a Mediterranean diet or chocolate improves gut permeability and low-grade endotoxemia

Why Use Adipose-Derived Mesenchymal Stem Cells in Tendinopathic Patients: A Systematic Review

The aim of the present systematic review was to provide a clear overview of the clinical current research progress in the use of adipose-derived mesenchymal stem cells (ASCs) as an effective therapeutic option for the management of tendinopathies, pathologies clinically characterized by persistent mechanical pain and structural alteration of the tendons. The review was carried out using three databases (Scopus, ISI Web of Science and PubMed) and analyzed records from 2013 to 2021. Only English-language papers describing the isolation and manipulation of adipose tissue as source of ASCs and presenting ASCs as treatment for clinical tendinopathies were included. Overall, seven clinical studies met the inclusion criteria and met the minimum quality inclusion threshold. Data extraction and quality assessment were performed by groups of three reviewers. The available evidence showed the efficacy and safety of ASCs treatment for tendinopathies, although it lacked a clear description of the biomolecular mechanisms underlying the beneficial properties of ASCs

Angiogenetic effects of physical exercise in menopausal women

Introduction: With menopause women face many changes that may lead to the loss of health related fitness, especially if sedentary. In particular, the estrogens deficiency affects the endothelial function thus increasing the incidence of the cardiovascular diseases. The cardio-protective effects of physical exercise is at least partially due to its ability to improve the health of arterial walls by influencing the endothelial function. Nonetheless, a direct angiogenetic of the physical exercise cannot be ruled out. VEGF is an important modulator of vascular growth but there are contrasting results about its response to physical exercise. Aim of our study was to compare the effects of two aerobic training on the VEGF levels and on the angiogenesis in postmenopausal women. Material and Methods. 34 Postmenopausal women underwent a 13 weeks training. In order to analyse the angiogentic effects, plasmatic VEGF levels were analysed before (T0) and after the training (T1). Moreover, the ability of the T0 and T1 serum to chemoattract endothelial cells and to induce them to form tubes was analyzed. Results: All post-menopausal women increase VEGF (P=0,014) after training. In vitro tests evidenced that when cultured in presence of T1 serum, HUVEC cells improved their ability to form tube (P<0,001) as well as their calibre (P<0,001). Moreover, migration assays evidenced that after training the serum chemoattractive capacity increased significantly (P<0,001) capacity. Conclusion: Our data evidence that aerobic training influence the arterial wall physiology also inducing a angiogenetic affect

Looking into CALIPSO climatological products: Evaluation and suggestions from EARLINET

CALIPSO (Cloud-Aerosol Lidar and Pathfinder Satellite Observations) Level 3 (CL3) data were compared against EARLINET (European Aerosol Research Lidar Network) monthly averages obtained by profiles during satellite overpasses. Data from EARLINET stations of Évora, Granada, Leipzig, Naples and Potenza, equipped with advanced multi-wavelength Raman lidars were used for this study. Owing to spatial and temporal differences, we reproduced the CL3 filtering rubric onto the CALIPSO Level 2 data. The CALIPSO monthly mean profiles following this approach are called CALIPSO Level 3*, CL3*. This offers the possibility to achieve direct comparable datasets. In respect to CL3 data, the agreement typically improved, in particular above the areas directly affected by the anthropogenic activities within the planetary boundary layer. However in most of the cases a subtle CALIPSO underestimation was observed with an average bias of 0.03 km-1. We investigated the backscatter coefficient applying the same screening criteria, where the mean relative difference in respect to the extinction comparison improved from 15.2% to 11.4%. Lastly, the typing capabilities of CALIPSO were assessed outlining the importance of the correct aerosol type (and associated lidar ratio value) assessment to the CALIPSO aerosol properties retrieval