CXCL16/CXCR6 axis drives microglia/macrophages phenotype in physiological conditions and plays a crucial role in glioma

Microglia are patrolling cells that sense changes in the brain microenvironment and respond acquiring distinct phenotypes that can be either beneficial or detrimental for brain homeostasis. Anti-inflammatory microglia release soluble factors that might promote brain repair; however, in glioma, anti-inflammatory microglia dampen immune response and promote a brain microenvironment that foster tumor growth and invasion. The chemokine CXCL16 is expressed in the brain, where it is neuroprotective against brain ischemia, and it has been found to be over-expressed in glioblastoma (GBM). Considering that CXCL16 specific receptor CXCR6 is diffusely expressed in the brain including in microglia cells, we wanted to investigate the role of CXCL16 in the modulation of microglia cell activity and phenotype, and in the progression of glioma. Here we report that CXCL16 drives microglia polarization toward an anti-inflammatory phenotype, also restraining microglia polarization toward an inflammatory phenotype upon LPS and IFN? stimulation. In the context of glioma, we demonstrate that CXCL16 released by tumor cells is determinant in promoting glioma associated microglia/macrophages (GAMs) modulation toward an anti-inflammatory/pro-tumor phenotype, and that cxcr6ko mice, orthotopically implanted into the brain with GL261 glioma cells,survive longer compared to wild-type mice. We also describe that CXCL16/CXCR6 signaling acts directly on mouse glioma cells, as well as human primary GBM cells, promoting tumor cell growth, migration and invasion. All together these data suggest that CXCL16 signaling could represent a good target to modulate microglia phenotype in order to restrain inflammation or to limit glioma progression

Effective electrothermal analysis of electronic devices and systems with parameterized macromodeling

We propose a parameterized macromodeling methodology to effectively and accurately carry out dynamic electrothermal (ET) simulations of electronic components and systems, while taking into account the influence of key design parameters on the system behavior. In order to improve the accuracy and to reduce the number of computationally expensive thermal simulations needed for the macromodel generation, a decomposition of the frequency-domain data samples of the thermal impedance matrix is proposed. The approach is applied to study the impact of layout variations on the dynamic ET behavior of a state-of-the-art 8-finger AlGaN/GaN high-electron mobility transistor grown on a SiC substrate. The simulation results confirm the high accuracy and computational gain obtained using parameterized macromodels instead of a standard method based on iterative complete numerical analysis

Nonlinear vibrations of laminated and sandwich rectangular plates with free edges. Part 2: Experiments & comparisons

Large-amplitude (geometrically nonlinear) forced vibrations of completely free sandwich rectangular plates are investigated experimentally. Harmonic excitation is applied by using an electro-dynamic exciter and the plate vibration is measured by using laser Doppler vibrometers. A scanning laser Doppler vibrometer is used for experimental modal analysis since it provides non-contact vibration measurements with very high spatial resolution. The large-amplitude vibration experiments are carried out by using a single point laser Doppler vibrometer and a stepped-sine testing procedure. The nonlinear frequency response curves are obtained by increasing and decreasing the excitation frequency in very small steps at specific force amplitudes controlled in a closed-loop. The experimental results are compared to numerical simulations obtained by reduced-order models and show very good agreement. The nonlinear damping is experimentally obtained as a function of the vibration amplitude

Accurate Maximum Power Tracking in Photovoltaic Systems Affected by Partial Shading

A maximum power tracking algorithm exploiting operating point information gained on individual solar panels is presented. The proposed algorithm recognizes the presence of multiple local maxima in the power voltage curve of a shaded solar field and evaluates the coordinated of the absolute maximum. The effectiveness of the proposed approach is evidenced by means of circuit level simulation and experimental results. Experiments evidenced that, in comparison with a standard perturb and observe algorithm, we achieve faster convergence in normal operating conditions (when the solar field is uniformly illuminated) and we accurately locate the absolute maximum power point in partial shading conditions, thus avoiding the convergence on local maxima

Effects of lack of microRNA-34 on the neural circuitry underlying the stress response and anxiety

Stress-related psychiatric disorders, including anxiety, are complex diseases that have genetic, and environmental causes. Stressful experiences increase the release of prefrontal amygdala neurotransmitters, a response that is relevant to cognitive, emotional, and behavioral coping. Moreover, exposure to stress elicits anxiety-like behavior and dendritic remodeling in the amygdala. Members of the miR-34 family have been suggested to regulate synaptic plasticity and neurotransmission processes, which mediate stress-related disorders. Using mice that harbored targeted deletions of all 3 members of the miR-34-family (miR-34-TKO), we evaluated acute stress-induced basolateral amygdala (BLA)-GABAergic and medial prefrontal cortex (mpFC) aminergic outflow by intracerebral in vivo microdialysis. Moreover, we also examined fear conditioning/extinction, stress-induced anxiety, and dendritic remodeling in the BLA of stress-exposed TKO mice. We found that TKO mice showed resilience to stress-induced anxiety and facilitation in fear extinction. Accordingly, no significant increase was evident in aminergic prefrontal or amygdala GABA release, and no significant acute stress-induced amygdalar dendritic remodeling was observed in TKO mice. Differential GRM7, 5-HT2C, and CRFR1 mRNA expressionwas noted in the mpFC and BLA between TKO andWT mice. Our data demonstrate that the miR-34 has a critical function in regulating the behavioral and neurochemical response to acute stress and in inducing stress-related amygdala neuroplasticity

KCa3.1 channel inhibition sensitizes malignant gliomas to temozolomide treatment

Malignant gliomas are among the most frequent and aggressive cerebral tumors, characterized by high proliferative and invasive indexes. Standard therapy for patients, after surgery and radiotherapy, consists of temozolomide (TMZ), a methylating agent that blocks tumor cell proliferation. Currently, there are no therapies aimed at reducing tumor cell invasion. Ion channels are candidate molecular targets involved in glioma cell migration and infiltration into the brain parenchyma. In this paper we demonstrate that: i) blockade of the calcium-activated potassium channel KCa3.1 with TRAM-34 has co-adjuvant effects with TMZ, reducing GL261 glioma cell migration, invasion and colony forming activity, increasing apoptosis, and forcing cells to pass the G2/M cell cycle phase, likely through cdc2 de-phosphorylation; ii) KCa3.1 silencing potentiates the inhibitory effect of TMZ on glioma cell viability; iii) the combination of TMZ/TRAM-34 attenuates the toxic effects of glioma conditioned medium on neuronal cultures, through a microglia dependent mechanism since the effect is abolished by clodronate-induced microglia killing; iv) TMZ/TRAM-34 co-treatment increases the number of apoptotic tumor cells, and the mean survival time in a syngeneic mouse glioma model (C57BL6 mice implanted with GL261 cells); v) TMZ/TRAM-34 co-treatment reduces cell viability of GBM cells and cancer stem cells (CSC) freshly isolated from patients.Taken together, these data suggest a new therapeutic approach for malignant glioma, targeting both glioma cell proliferating and migration, and demonstrate that TMZ/TRAM-34 co-treatment affects both glioma cells and infiltrating microglia, resulting in an overall reduction of tumor cell progression

RAASi Therapy Attenuates the Association between 24-h Urinary Potassium Excretion and Dietary Potassium Intake in CKD Patients

The aim of this study was to evaluate urinary potassium (K) excretion as a reliable marker of dietary K intake, in a cohort of CKD patients with or without Renin-Angiotensin-Aldosterone System (RAAS) inhibitor therapy. One hundred and thirty-eight consecutive out-patients (51 f and 87 m) aged 60 +/- 13 years and affected by CKD stage 3-4, who were metabolically and nutritionally stable, entered the study between November 2021 and October 2022. No difference was observed between patients with (n = 85) or without (n = 53) RAAS inhibitor therapy, regarding dietary intakes, blood biochemistry, and 24-h urine excretion parameters. Considering all patients, urinary K showed a weak relationship with eGFR (r = 0.243, p < 0.01), and with dietary K intake (r = 0.184, p < 0.05). Serum K was not associated with dietary K intake, but an inverse relationship was observed with eGFR (r = -0.269, p < 0.01). When patients were examined depending on whether they were receiving RAAS inhibitor therapy, the weak inverse relationship between serum K and eGFR was maintained in both groups. Conversely, urinary K excretion remained positively associated with dietary K intake only in the no RAAS inhibitor group. In conclusion, 24-h urine K excretion may be used as a surrogate of K intake, but RAAS inhibitor therapy reduces the association between 24-h urine K excretion and dietary K intake in CKD patients

Supplementation of Rosemary extract in the diet of Nero Siciliano pigs: evaluation of the antioxidant properties on meat quality.

In the present study, the effect of Rosmarinus officinalis L. dietary supplementation on meat quality and oxidative stability of Nero Siciliano pigs was examined. During the growing–fattening period, 32 Nero Siciliano pigs were allotted into two treatment groups consisting of 8 replicates with 2 pigs per pen. For 90 days, the animals received a basal diet: one group (CTR) was not dietary supplemented, whereas the other group received (1 g/kg) rosemary extract (ROX). Supplementation with rosemary extract significantly improved the polyunsaturated fatty acid content of the meat, which showed higher values in the meat of the ROX group compared with the CTR group (P0.05). Color measurement performed in the present study on meat samples from the two dietary treatments showed that redness decreased (P=0.046) and hue values increased (P=0.036), indicating that a deterioration of the initial color occurred and that the rosemary extract was ineffective in preventing color deterioration. Nevertheless, the lightness, yellowness and chroma color descriptors showed similar values in relation to dietary treatment (P>0.05). Considering the nutritional value of meat as an important contributor to the overall quality, the results obtained in this study support the possibility of the dietary supplementation with R. officinalis L. extract in pigs as a functional additive in livestock feeding

Slaughtering traits and meat quality of Cinisara cattle native Italian breed

The aim of our study was to make an initial contribution to carcass traits and meat quality for typing and product certification, using sixteen male (M) and twelve female (F) Cinisara cattle, a native Italian breed. The animals were sampled in the most representative farms of the Consortium of Cinisara breed. Carcass traits of the Cinisara males showed significantly higher carcass weight and SEUROP scores in comparison to the females, while similar values were observed for fatness scores. As regards meat quality, lightness (M 44.90 vs F 43.25), redness index (M 18.03 vs F 17.86), hue angle (M 21.71 vs F 23.76), cooking losses (M 24.44% vs F 24.98%), tenderness (M 3.36 kg/cm2 vs F 3.41 kgf/cm2), protein (M 22.58% vs F 21.84%) and fat (M 1.88% vs F 2.63%) showed no significant differences between males and females. No data are available in the literature for Cinisara cattle; therefore, our results may be considered as an original set of knowledge useful for the salvage of this endangered, local, native breed