Free radical grafting kinetics of acrylamide onto a blend of starch/chitosan/alginate

Grafting of monomer onto polymer backbone is one of the effective and accessible methods for the chemical modification of polysaccharides. Grafting of acrylamide (AAm) onto polysaccharides blend (PsB) composed of starch, chitosan and alginate has been carried out using potassium persulfate (KPS) as an initiator. The kinetics of the grafting polymerization also has been studied. The grafting parameters have been evaluated by changing the initial concentrations of AAm from 8 to 16 g, PsB from 6 to 14 g and KPS from 0.2 to 1 g. Evidence of grafting has been obtained from FTIR, XRD and TGA. The kinetics of the grafting polymerization also has been studied. The grafting rate equation of the produced hydrogel (PsB-g-AAm) hydrogel has been expressed by: Rg = k[AAm] [PsB]^0.5 [KPS]^0.5. The grafting rate is a first order dependence to [AAm] initial concentration and square root to [PsB] and [KPS] initial concentrations in the used concentrations range.     

Modulation of vigabatrin induced cerebellar injury: the role of caspase-3 and RIPK1/RIPK3-regulated cell death pathways

Journal of Molecular Histology - Vigabatrin is the drug of choice in resistant epilepsy and infantile spasms. Ataxia, tremors, and abnormal gait have been frequently reported following its use...     

Proteomics characterization of cell model with renal fibrosis phenotype: osmotic stress as fibrosis triggering factor

Renal fibroblasts are thought to play a major role in the development of renal fibrosis (RF). The mechanisms leading to this renal alteration remain poorly understood. We performed differential proteomic analyses with two established fibroblast cell lines with RF phenotype to identify new molecular pathways associated with RF. Differential 2-DE combined with mass spectrometry analysis revealed the alteration of more than 30 proteins in fibrotic kidney fibroblasts (TK188) compared to normal kidney fibroblast (TK173). Among these proteins, markers of the endoplasmic reticulum (ER) stress- and the unfolded protein response (UPR) pathway (GRP78, GRP94, ERP57, ERP72, and CALR) and the oxidative stress pathway proteins (PRDX1, PRDX2, PRDX6, HSP70, HYOU1) were highly up-regulated in fibrotic cells. Activation of these stress pathways through long time exposition of TK173, to high NaCl or glucose concentrations resulted in TK188 like phenotype. Parallel to an increase in reactive oxygen species, the stressed cells showed significant alteration of fibrosis markers, ER-stress and oxidative stress proteins. Similar effects of osmotic stress could be also observed on renal proximal tubule cells. Our data suggest an important role of the ER-stress proteins in fibrosis and highlights the pro-fibrotic effect of osmotic stress through activation of oxidative stress and ER-stress pathways.     

Identification of Biomarkers of Human Skin Ageing in Both Genders. Wnt Signalling - A Label of Skin Ageing?

The goal of our work has been to investigate the mechanisms of gender-independent human skin ageing and examine the hypothesis of skin being an adequate model of global ageing. For this purpose, whole genome gene profiling was employed in sun-protected skin obtained from European Caucasian young and elderly females (mean age 26.7±4 years [n1 = 7] and 70.75±3.3 years [n2 = 4], respectively) and males (mean age 25.8±5.2 years [n3 = 6] and 76±3.8 years [n4 = 7], respectively) using the Illumina array platform. Confirmation of gene regulation was performed by real-time RT-PCR and immunohistochemistry. 523 genes were significantly regulated in female skin and 401 genes in male skin for the chosen criteria. Of these, 183 genes exhibited increased and 340 decreased expression in females whereas 210 genes showed increased and 191 decreased expression in males with age. In total, 39 genes were common in the target lists of significant regulated genes in males and females. 35 of these genes showed increased (16) or decreased (19) expression independent of gender. Only 4 overlapping genes (OR52N2, F6FR1OP2, TUBAL3 and STK40) showed differential regulation with age. Interestingly, Wnt signalling pathway showed to be significantly downregulated in aged skin with decreased gene and protein expression for males and females, accordingly. In addition, several genes involved in central nervous system (CNS) ageing (f.i. APP, TAU) showed to be expressed in human skin and were significanlty regulated with age. In conclusion, our study provides biomarkers of endogenous human skin ageing in both genders and highlight the role of Wnt signalling in this process. Furthermore, our data give evidence that skin could be used as a good alternative to understand ageing of different tissues such as CNS.     

Synaptic and Extrasynaptic NMDA Receptors Are Gated by Different Endogenous Coagonists

N-methyl-d-aspartate receptors (NMDARs) are located in neuronal cell membranes at synaptic and extrasynaptic locations, where they are believed to mediate distinct physiological and pathological processes. Activation of NMDARs requires glutamate and a coagonist whose nature and impact on NMDAR physiology remain elusive. We report that synaptic and extrasynaptic NMDARs are gated by different endogenous coagonists, d-serine and glycine, respectively. The regionalized availability of the coagonists matches the preferential affinity of synaptic NMDARs for d-serine and extrasynaptic NMDARs for glycine. Furthermore, glycine and d-serine inhibit NMDAR surface trafficking in?a subunit-dependent manner, which is likely to influence NMDARs subcellular location. Taking advantage of this coagonist segregation, we demonstrate that long-term potentiation and NMDA-induced neurotoxicity rely on synaptic NMDARs only. Conversely, long-term depression requires both synaptic and extrasynaptic receptors. Our observations provide key insights into the operating mode of NMDARs, emphasizing functional distinctions between synaptic and extrasynaptic NMDARs in brain physiology.     

A Potential Inhibitory Profile of Liver CD68+ Cells during HCV Infection as Observed by an Increased CD80 and PD-L1 but Not CD86 Expression

AimThe lack of potent innate immune responses during HCV infection might lead to a delay in initiating adaptive immune responses. Kupffer cells (KCs) and liver-infiltrating monocytes/macrophages (CD68⁺ cells) are essential to establish effective anti-HCV responses. They express co-stimulatory molecules, CD80 and CD86. CD86 upregulation induces activator responses that are then potentially regulated by CD80. The relative levels of expression of CD80, CD86 and the inhibitory molecule, PD-L1, on CD68⁺ cells modulate T cell activation. A few studies have explored CD80 and PD-L1 expression on KCs and infiltrating monocytes/macrophages in HCV-infected livers, and none investigated CD86 expression in these cells. These studies have identified these cells based on morphology only. We investigated the stimulatory/inhibitory profile of CD68⁺ cells in HCV-infected livers based on the balance of CD80, CD86 and PD-L1 expression.MethodsCD80, CD86 and PD-L1 expression by CD68⁺ cells in the lobular and portal areas of the liver of chronic HCV-infected (n = 16) and control (n = 14) individuals was investigated using double staining immunohistochemistry.ResultsThe count of CD68⁺ KCs in the lobular areas of the HCV-infected livers was lower than that in the control (p = 0.041). The frequencies of CD68⁺CD80⁺ cells and CD68⁺PD-L1⁺ cells in both lobular and total areas of the liver were higher in HCV-infected patients compared with those in the control group (p = 0.001, 0.031 and 0.007 respectively). Moreover, in the lobular areas of the HCV-infected livers, the frequency of CD68⁺CD80⁺ cells was higher than that of CD68⁺CD86⁺ and CD68⁺PD-L1⁺ cells. In addition, the frequencies of CD68⁺CD80⁺ and CD68⁺CD86⁺ cells were higher in the lobular areas than the portal areas.ConclusionsOur results show that CD68⁺ cells have an inhibitory profile in the HCV-infected livers. This might help explain the delayed T cell response and viral persistence during HCV infection.     

Hesperidin suppressed hepatic precancerous lesions via modulation of exophagy in rats

The enormous cost of modern medicines warrants alternative strategies for the better management of hepatocellular carcinoma. Recently, exosomes have been shown to relay the oncogenic information through the horizontal transfer of RNAs between the cells. In this study, we modulated exosomal production and autophagy (exophagy) by the administration of hesperidin and evaluated its effect on the development of hepatic precancerous lesion (HPC) in rats. Diethylnitrosamine and 2-acetylaminofluorene were used in vivo to induce HPC in rats. Rats were allocated into five groups: naïve, HPC, and three hesperidin treated (50, 100, and 200 mg/kg/d; orally) for 4 consecutive days per week for 16 weeks. Liver tissues and blood samples were collected for histopathological, immunohistochemical, and transmission electron microscope examinations, liver function, alfa-fetoprotein level, and isolation of exosomal and autophagy RNAs. Hesperidin administration showed hepato-protective effects and improved the microscopic hepatic features with a decrease in glutathione S-transferase placental precancerous foci and the abundance of exosomes in liver tissues. Hesperidin improved liver function with a significant decrease in alfa-fetoprotein levels. Hesperidin dose-dependently decreased exosomal RAB11A messsenger RNA and long noncoding RNA-RP11-583F2.2 along with the increase in exosomal miR-1298, involved in the exophagy process. In conclusion, hesperidin likely suppresses liver carcinogenesis in rat model via the modulation of exosomal secretion and autophagy.     

Repigmentation in vitiligo: position paper of the Vitiligo Global Issues Consensus Conference

The Vitiligo Global Issues Consensus Conference (VGICC), through an international e‐Delphi consensus, concluded that ‘repigmentation’ and ‘maintenance of gained repigmentation’ are essential core outcome measures in future vitiligo trials. This VGICC position paper addresses these core topics in two sections and includes an atlas depicting vitiligo repigmentation patterns and color match. The first section delineates mechanisms and characteristics of vitiligo repigmentation, and the second section summarizes the outcomes of international meeting discussions and two e‐surveys on vitiligo repigmentation, which had been carried out over 3 yr. Treatment is defined as successful if repigmentation exceeds 80% and at least 80% of the gained repigmentation is maintained for over 6 months. No agreement was found on the best outcome measure for assessing target or global repigmentation, therefore highlighting the limitations of e‐surveys in addressing clinical measurements. Until there is a clear consensus, existing tools should be selected according to the specific needs of each study. A workshop will be conducted to address the remaining issues so as to achieve a consensus.