Guthriespivey9376

Fetească neagră and Pinot noir grape pomace extracts have a rich content of polyphenols and in vitro antioxidant effect. Fermented samples had higher polyphenol content, but fresh samples had better antioxidant activity. Pretreatment with grape pomace extracts reduced inflammation-induced oxidative stress in a concentration-dependent way, fresh samples being more efficient. The malignant cells' proliferation was inhibited by all grape pomace extracts, fermented Fetească neagră extracts having the strongest effect. Conclusion fresh and fermented pomace extracts of Vitis vinifera L. varieties Fetească neagră and Pinot noir cultivated in a Romanian wine region have antioxidant, anti-inflammatory and antiproliferative effects.Cisplatin-induced acute kidney injury (CIAKI) is a common complication in patients receiving cisplatin-based chemotherapy. But the effective therapies for CIAKI are not available. Retinoic acid (RA), the main derivative of vitamin A, has the potential to reduce inflammation and fibrosis in renal injury. However, the effect and mechanism of RA on CIAKI are still unclear. The aim of this study is to investigate whether RA can alleviate CIAKI through activation of autophagy. In this study, we evaluated the effect of RA, RA's effect on autophagy and apoptosis after cisplatin-induced injury on renal tubular epithelial cells (RTECs) by LDH assay, immunoblotting and TUNEL staining. Then we established Atg5flox/floxCagg-Cre mice in which Cagg-Cre is tamoxifen inducible, and Atg5 is conditional deleted after tamoxifen injection. The effect of RA and RA's effect on autophagy on CIAKI model were evaluated by biochemical assessment, hematoxylin and eosin (HE) staining, and immunoblotting in the control and autophagy deficient mice. In vitro, RA protected RTECs against cisplatin-induced injury, activated autophagy, and inhibited cisplatin-induced apoptosis. In vivo, RA attenuated cisplatin-induced tubular damage, shown by improved renal function, decreased renal cast formation, decreased NGAL expression, and activated autophagy in the control mice. Furthermore, the nephrotoxicity of cisplatin was aggravated, and the protective effect of RA was attenuated in autophagy deficient mice, indicating that RA works in an autophagy-dependent manner on CIAKI. RA activates autophagy and alleviates CIAKI in vivo and in vitro.Thus RA may be a renoprotective adjuvant for cisplatin-based chemotherapy.Human α1-antitrypsin (AAT) is an abundant acute phase glycoprotein expressing anti-protease and immunomodulatory activities, and is used as a biopharmaceutical to treat patients with inherited AAT deficiency. The pleiotropic properties of AAT provide a rationale for using this therapy outside of inherited AAT deficiency. Therapy with AAT is administrated intravenously, yet the alternative routes are being considered. To examine the putative transepidermal application of AAT we used epiCS®, the 3D human epidermis equivalents reconstructed from human primary epidermal keratinocytes. We topically applied various concentrations of AAT protein with a constant volume of 50 µl, prepared in Hank's balance solution, HBSS, to epiCS cultured under bas\al condition or when culture medium supplemented with 100 µg/ml of a combined bacterial lipopolysaccharide (LPS) and peptidoglycan (PGN) mixture. AAT freely diffused across epidermis layers in a concentration and time-dependent manner. Within 18 h topically provided 0.2 mg AAT penetrated well the stratum corneum and localizes within the keratinocytes. The treatments with AAT did not induce obvious morphological changes and damages in keratinocyte layers. As expected, LPS/PGN triggered a strong pro-inflammatory activation of epiCS. AAT exhibited a limited capacity to neutralize the effect of LPS/PGN, but more importantly, it lowered expression of IL-18 and IL-8, and preserved levels of filaggrin, a key protein for maintaining the epidermal barrier integrity. Our findings suggest that the transepidermal route for delivering AAT is worthwhile to explore further. PIKIII If successful, this approach may offer an easy-to-use therapy with AAT for skin inflammatory diseases.Lipids play a major role for several brain functions, including cognition and memory. There is a series of work on individual lipids showing involvement in memory mechanisms, a concise lipidome was not reported so far. Moreover, there is no evidence for age-related memory decline and there is only work on brain of young vs. aging animals. Aging animals, however, are not a homogeneous group with respect to memory impairments, thus animals with impaired and unimpaired memory can be discriminated. Following recent studies of hippocampal lipid profiles and hypothalamus controlled hormone profiles, the aim of this study was to compare hypothalamic, lipidomic changes in male Sprague-Dawley rats between young (YM), old impaired (OMI) and old unimpaired (OMU) males. Grouping criterions for aged rats were evaluated by testing them in a spatial memory task, the hole-board. YMs were also tested. Subsequently brains were removed, dissected and hypothalami were kept at -80°C until sample preparation and analysis on liquidcessity of evaluating the cognitive status of aged subjects by behavioral tests results in more specific detection of critical lipids in memory decline, on which now can be focused in subsequent memory studies in animals and humans.Cognitive impairment is a key clinical feature of ischemic leukoaraiosis (ILA); however, the underlying neurobiological mechanism is still unclear. ILA has been associated with widespread gray and white matter (WM) damage mainly located in cortical-cortical and cortico-subcortical pathways. A total of 36 patients with ILA (Fazekas rating score ≥2) and 31 healthy controls (HCs) underwent comprehensive neuropsychological assessments (covering four cognitive domains, i.e., information processing speed, episodic memory, executive and visuospatial function) and resting-state functional MRI scans. Graph theory-based analyses were employed to explore the topological organization of the brain connectome in ILA patients, and we further sought to explore the associations of connectome-based metrics and neuropsychological performances. An efficient small-world architecture in the functional brain connectome was observed in the ILA and control groups. Moreover, compared with the HCs, the ILA patients showed increased path length and decreased network efficiency (i.