Search

A relevant percentage of IgAN patients experience a progressive decline in kidney function. According to the KDIGO guidelines, proteinuria and eGFR are the only validated prognostic markers. The role of interstitial macrophages in kidney biopsies of IgAN patients and the outcome of patients treated with renin–angiotensin system inhibitors (RASBs) alone or combined with glucocorticoids were evaluated. Clinical and laboratory records (age, gender, hypertension, hematuria, proteinuria, eGFR, serum creatinine, and therapy), MEST-C parameters of the Oxford classification, C4d deposition, peritubular capillaries, and glomerular and interstitial macrophages in 47 IgAN patients undergoing kidney biopsy consecutively between 2003 and 2016 were examined. A high number of interstitial macrophages significantly correlated with peritubular capillary rarefaction and impairment of kidney function. Cox’s multivariable regression analysis revealed that a value > 19.5 macrophages/HPF behaved as an independent marker of an unfavorable outcome. Patients exhibiting > 19.5 macrophages/HPF treated at the time of diagnosis with RASBs combined with methylprednisolone had an estimated probability of a favorable outcome higher than patients treated with RASBs alone. Thus, a value > 19.5 macrophages/HPF in IgAN biopsies can predict an unfavorable outcome and endorse a well-timed administration of glucocorticoids. Studies evaluating urine biomarkers associated with peritubular capillary rarefaction in patients with marked macrophage infiltration may help personalized treatment decisions.

GDF11 is a member of the TGF-β superfamily that was recently implicated as potential "rejuvenating" factor, which can ameliorate metabolic disorders. The main objective of the presented study was to closely characterize the role of GDF11 signaling in the glucose homeostasis and in the differentiation of white adipose tissue.We performed microscopy imaging, biochemical and transcriptomic analyses of adipose tissues of 9 weeks old ob/ob mice and murine and human pre-adipocyte cell lines.Our in vivo experiments employing GDF11 treatment in ob/ob mice showed improved glucose/insulin homeostasis, decreased weight gain and white adipocyte size. Furthermore, GDF11 treatment inhibited adipogenesis in pre-adipocytes by ALK5-SMAD2/3 activation in cooperation with the WNT/β-catenin pathway, whose inhibition resulted in adipogenic differentiation. Lastly, we observed significantly elevated levels of the adipokine hormone adiponectin and increased glucose uptake by mature adipocytes upon GDF11 exposure.We show evidence that link GDF11 to adipogenic differentiation, glucose, and insulin homeostasis, which are pointing towards potential beneficial effects of GDF11-based "anti-obesity" therapy.

Several studies demonstrated that melatonin treatment prevents tissue damage in various models of oxidative stress (1). Experiments have shown that chronic nicotine administration caused oxidant damage in various organs by increasing lipid peroxidation products and decreasing the activity of endogenous antioxidants (2). The aim of this study was to investigate the effects of melatonin treatment on nicotine-induced oxidative changes in rat kidney and to explore the possible mechanisms of action. Three groups of rats were used as controls (the first without treatment, the second with melatonin alone and the third with nicotine alone). The last group of rats was orally treated with nicotine and melatonin for 28 days. Morphological changes in kidney were evaluated by histological procedures and immunohistochemical analysis using inflammation (NFkB and IL-6) and oxidative stress (SOD, CAT and iNOS) markers. Experiments performed demonstrated that nicotine administration increases inflammation and oxidative stress. Melatonin has a protective effect against nicotine kidney toxicity through an inhibition of inflammation and consequent oxidative damage. These data suggest that melatonin supplementation effectively counteracts the deleterious effect of chronic nicotine administration on kidney and attenuates oxidative damage possibly by its anti-inflammatory and antioxidant effects.This work was supported by grants from University of Brescia (EX 60%)., Italian Journal of Anatomy and Embryology, Vol. 121, No. 1 (Supplement) 2016

Chronic inflammatory fibro-proliferative changes leading to atherosclerotic plaques are considered hallmark of cardiovascular diseases [1]. Atherosclerosis pathogenesis is a complex entity, which has not been fully understood; however, many studies have demonstrated the role of oxidative stress and inflammation in its development. Melatonin effects on inflammation and oxidative stress process have been demonstrated in the last ten-year literature [2]. However, its role(s) and mechanism(s) of action as a therapeutic tool against atherosclerosis remain largely unexplored. Our aims were to assess the role of melatonin in the onset and developing of atherosclerotic plaques through radiologic and morphometrical tools in 20 apolipoprotein-E knockout (ApoE) mice fed with Western diet (42% calories from fat). 10/20 mice were treated with melatonin (10 mg/kg per os). 18F-FDG PET-CT is a widely used tool to assess inflammatory changes, even before macroscopic changes have taken place. Glucose metabolism is known to be higher in areas of inflammation due to an increased expression of GLUT transporters on the cell membranes both in animals and humans. Using this feature PET/CT is able to determinate metabolic cellular changes and therefore it can be used as biomarker of atherosclerosis. All mice were scanned both before starting melatonin treatment and at the end of the study. After the last scan mice were sacrificed and vascular remodeling, oxidative stress and inflammation at aortic arch level were evaluated. CT-corrected PET datasets were used for computation of SUVmax. Atherosclerotic vascular remodeling, oxidative stress and inflammation levels were significantly more conspicuous in the control cohort, compared to the treated mice (p≤0.05). 18F-FDG PET/CT did not show significant difference in SUVmax. In summary, also in vivo, melatonin may have a protective effect in the atherosclerotic pathogenesis. Flamma S.p.A.-Italy (www.flammagroup.com) provided with melatonin. Financial supports: Fondazione Cariplo e Regione Lombardia “New opportunities and ways towards ERC” (Project 2014-2256) and University of California - Radiology and Biomedical Imaging Nuclear Medicine Section., Italian Journal of Anatomy and Embryology, Vol. 122, No. 1 (Supplement) 2017

Sirtuin 1 (SIRT1), a member of the silencing information regulator 2 enzymes called sirtuins, is emerging as a master-regulator of metabolic functions like energy balance, mitochondrial health, browning of white adipose tissue, lipolysis. To best characterize its role in obesity, we analysed metabolic and morphological changes induced in SIRT1 heterozygous mice (HET) [1] by a high fat diet (5.4 Kcal/g from fat-lard TD03584-Envigo) in comparison with C57BL6/J mice. Male C57BL6/J (WT) and HET mice received a standard maintenance diet (SD) (2.9 Kcal/g) or a high fat (HF) diet for 16 weeks from 12 to 28 weeks of age. Hepatic and epididymal white adipose depot (eWAT) reactions to the obesogenic diet were focused on hypoxia, inflammation, and endoplasmic reticulum stress. At euthanasia, blood was collected and the liver and eWAT removed for morphological analysis. WT HF and HET HF groups positively correlated with glucose intolerance, hepatomegaly and adipogenesis when compared with SD groups. Remarkably hepatosteatosis, fibrosis and inflammation were exacerbated in HET HF. Oxidative damage and abnormal lipogenesis were confirmed by elevated 4HNE and SREBP1 expressions. Hepatic mitochondria revealed myelinic figures and abnormal ER-mitochondria juxtapositions in HET HF [2]. eWAT adipocytes showed reduced perilipin but strong TNF-alpha and GRP78 signals in crown-like structures. In conclusion, HET HF mice might represent an intriguing animal model to best understand the complex pathogenesis of obesity and related disorders., Italian Journal of Anatomy and Embryology, Vol. 122, No. 1 (Supplement) 2017