Pathogenesis of Renal Disease in Systemic Lupus Erythematosus—The Role of Autoantibodies and Lymphocytes Subset Abnormalities

Lupus nephritis (LN) is a common and severe organ manifestation of systemic lupus erythematosus (SLE), and is associated with significant patient morbidity and mortality. Autoantibodies and aberrations in lymphocyte subsets have putative roles in the pathogenesis of SLE and LN, and might reflect disease activity and are amenable to immunosuppressive treatments. Anti-DNA is one of the well-studied autoantibodies, which correlates with disease activity and has direct nephritogenic effects on resident renal cells and various glomerular components. Other important autoantibodies in the pathogenesis of LN include anti-C1q, anti-α-actinin and anti-nucleosome antibodies. Changes in naive and memory B cells and plasma cells have been observed in SLE and LN patients. These B cell subsets exert diverse effects during pathogenesis of LN such as production of autoantibodies, secretion of proinflammatory and anti-inflammatory cytokines and presentation of auto-antigens to effector cells. Aberration of T lymphocytes, especially the T-helper subsets, is also highly pertinent in the development of LN. In this context, important T helper subsets include Th1, Th2, Th9, Th17, T_Reg and follicular T-helper cells. The growing knowledge on these autoantibodies and lymphocyte subset abnormalities will enhance our understanding of SLE and LN, and hence help devise better strategies for disease monitoring and treatment.     

Listeria Meningitis Complicating Alemtuzumab Treatment in Multiple Sclerosis—Report of Two Cases

Alemtuzumab, a humanized monoclonal antibody targeting the surface molecule CD52, leads to a rapid depletion of immune cells in the innate and adaptive immune system. In phase 2 and 3 trials in multiple sclerosis (MS), infections have been reported more frequently in alemtuzumab than in interferon beta treated patients. Here we report two patients treated with alemtuzumab for MS developing Listeria meningitis few days after the first infusion cycle. Both patients recovered completely after prompt diagnosis and adequate treatment. Physicians and patients should be aware of this serious, but treatable complication.     

Brain-Specific Cytoskeletal Damage Markers in Cerebrospinal Fluid: Is There a Common Pattern between Amyotrophic Lateral Sclerosis and Primary Progressive Multiple Sclerosis?

Many neurodegenerative disorders share a common pathophysiological pathway involving axonal degeneration despite different etiological triggers. Analysis of cytoskeletal markers such as neurofilaments, protein tau and tubulin in cerebrospinal fluid (CSF) may be a useful approach to detect the process of axonal damage and its severity during disease course. In this article, we review the published literature regarding brain-specific CSF markers for cytoskeletal damage in primary progressive multiple sclerosis and amyotrophic lateral sclerosis in order to evaluate their utility as a biomarker for disease progression in conjunction with imaging and histological markers which might also be useful in other neurodegenerative diseases associated with affection of the upper motor neurons. A long-term benefit of such an approach could be facilitating early diagnostic and prognostic tools and assessment of treatment efficacy of disease modifying drugs.     

Are Cerebrospinal Fluid Biomarkers Useful in Predicting the Prognosis of Multiple Sclerosis Patients?

Multiple sclerosis (MS) is the prototypical inflammatory demyelinating disorder of the central nervous system (CNS). Although many advances have been made in the comprehension of its pathogenesis, the etiology is still unknown. The complexity of MS reflects in the extreme variability of the clinical manifestations and clinical course both between and within patients, in addition to immunopathological mechanisms and response to treatment. Several prognostic factors have been suggested in large scale studies, but predictions in individual cases are difficult to make. Cerebrospinal fluid (CSF) biomarkers, such as 14-3-3, tau, and cystatin C are promising sources of prognostic information with a good potential of quantitative measure, sensitivity, and reliability. However, none has shown sufficient reproducibility to be applied in clinical practice. Here we review the current literature addressing the above mentioned biomarkers as MS severity predictors at an early stage.     

Modeling Neuronal Pathology in Yeast: Insights into the Molecular Basis of Parkinson’s Disease

The budding yeast Saccharomyces cerevisiae has been extensively studied as a model organism for biochemical and genetic research for almost a century. In recent years, yeast has been successfully used to model many aspects of human diseases. These “humanized” yeast models have had a profound influence on our understanding of the molecular events underlying neurodegenerative disorders. Yeast models can recapitulate important molecular events that occur in neurodegeneration, and provide clues about the underpinnings of toxicity in animal models of disease. Moreover, yeast models have also served as a powerful tool for drug discovery. In this mini-review, we describe yeast models that have been used to study the molecular aspects of Parkinson’s disease pathology and recent advances in the field based on these models.     

Role of microstructure in the grinding and polishing of α-sialon ceramics

The grinding and polishing behaviour of three tailored α-sialon microstructures made of the same chemical composition: fine-grained, bimodal and large elongated-grained, were determined. The fine-grained microstructure was characterised by extensive lateral cracks in the grinding process and widespread grain pullout during the mechanical polishing; in contrast, the large elongated-grained microstructure exhibited high grinding damage resistance, and a defect-free, mirror-like surface after mechanical polishing. The bimodal microstructure showed an intermediate behaviour during both processes. The material removal mechanisms during grinding and polishing were analysed and modelled as a function of grain size and aspect ratio.     

P2X and P2Y Receptors—Role in the Pathophysiology of the Nervous System

Purinergic signalling plays a crucial role in proper functioning of the nervous system. Mechanisms depending on extracellular nucleotides and their P2 receptors also underlie a number of nervous system dysfunctions. This review aims to present the role of purinergic signalling, with particular focus devoted to role of P2 family receptors, in epilepsy, depression, neuropathic pain, nervous system neoplasms, such as glioma and neuroblastoma, neurodegenerative diseases like Parkinson’s disease, Alzheimer’s disease and multiple sclerosis. The above-mentioned conditions are associated with changes in expression of extracellular ectonucleotidases, P2X and P2Y receptors in neurons and glial cells, as well as releasing considerable amounts of nucleotides from activated or damaged nervous tissue cells into the extracellular space, which contributes to disturbance in purinergic signalling. The numerous studies indicate a potential possibility of using synthetic agonists/antagonists of P2 receptors in treatment of selected nervous system diseases. This is of particular significance, since numerous available agents reveal a low effectiveness and often produce side effects.     

New Role of Hispidulin in Lipid Metabolism: PPARα Activator

Hispidulin is a naturally occurring flavonoid isolated from a traditional Chinese medicinal herb, Saussurea involucrata. In this study, the regulating role of hispidulin on the mRNA expression level of enzymes involved in lipid metabolism was examined in vitro and in vivo. Moreover, the in vivo lipid‐modulating effect of hispidulin was compared with that of fenofibrate, a classical PPARα agonist. Our results in present study demonstrated that hispidulin can directly bind to and activate PPARα as an agonist and thus modulate the downstream lipid‐metabolizing genes. Moreover, hispidulin could attenuate dyslipidemia in high fat diet induced dyslipidemia rat model. Although further studies are needed, this study provided evidence for the potential use of hispidulin in dyslipidemia management.     

The Role of α1-Adrenoceptor Antagonists in the Treatment of Prostate and Other Cancers

This review evaluates the role of α-adrenoceptor antagonists as a potential treatment of prostate cancer (PCa). Cochrane, Google Scholar and Pubmed were accessed to retrieve sixty-two articles for analysis. In vitro studies demonstrate that doxazosin, prazosin and terazosin (quinazoline α-antagonists) induce apoptosis, decrease cell growth, and proliferation in PC-3, LNCaP and DU-145 cell lines. Similarly, the piperazine based naftopidil induced cell cycle arrest and death in LNCaP-E9 cell lines. In contrast, sulphonamide based tamsulosin did not exhibit these effects. In vivo data was consistent with in vitro findings as the quinazoline based α-antagonists prevented angiogenesis and decreased tumour mass in mice models of PCa. Mechanistically the cytotoxic and antitumor effects of the α-antagonists appear largely independent of α 1-blockade. The proposed targets include: VEGF, EGFR, HER2/Neu, caspase 8/3, topoisomerase 1 and other mitochondrial apoptotic inducing factors. These cytotoxic effects could not be evaluated in human studies as prospective trial data is lacking. However, retrospective studies show a decreased incidence of PCa in males exposed to α-antagonists. As human data evaluating the use of α-antagonists as treatments are lacking; well designed, prospective clinical trials are needed to conclusively demonstrate the anticancer properties of quinazoline based α-antagonists in PCa and other cancers.     

Sodium-Calcium Exchanger 2: A Pivotal Role in Oxaliplatin Induced Peripheral Neurotoxicity and Axonal Damage?

Oxaliplatin (OHP)-induced peripheral neurotoxicity (OIPN) is a frequent adverse event of colorectal cancer treatment. OIPN encompasses a chronic and an acute syndrome. The latter consists of transient axonal hyperexcitability, due to unbalance in Na⁺ voltage-operated channels (Na⁺VOC). This leads to sustained depolarisation which can activate the reverse mode of the Na⁺/Ca²⁺ exchanger 2 (NCX2), resulting in toxic Ca²⁺ accumulation and axonal damage (ADa). We explored the role of NCX2 in in vitro and in vivo settings. Embryonic rat Dorsal Root Ganglia (DRG) organotypic cultures treated with SEA0400 (SEA), a NCX inhibitor, were used to assess neuroprotection in a proof-of-concept and pilot study to exploit NCX modulation to prevent ADa. In vivo, OHP treated mice (7 mg/Kg, i.v., once a week for 8 weeks) were compared with a vehicle-treated group (n = 12 each). Neurophysiological and behavioural testing were performed to characterise acute and chronic OIPN, and morphological analyses were performed to detect ADa. Immunohistochemistry, immunofluorescence, and western blotting (WB) analyses were also performed to demonstrate changes in NCX2 immunoreactivity and protein expression. In vitro, NCX inhibition was matched by ADa mitigation. In the in vivo part, after verifyingboth acute and chronic OIPN had ensued, we confirmed via immunohistochemistry, immunofluorescence, and WB that a significant NCX2 alteration had ensued in the OHP group. Our data suggest NCX2 involvement in ADa development, paving the way to a new line of research to prevent OIPN.     

The Role of the Liquid‐Solid Interface in the Preparation of Supported Catalysts

The contribution of the Interface Science to the preparation of supported catalysts during the last two decades is presented. It is illustrated how the concepts and the methodologies of the Interface Science could be effectively used for an in‐depth understanding of the phenomena involved in the initial preparation step. This, extremely critical step, concerns the deposition of transition metal species containing the active elements, from an impregnation solution, onto the surface of common catalytic supports. Moreover, the aforementioned concepts and methodologies allow the regulation of the mode of interfacial deposition and the local structure of the deposited species and, thus, the surface characteristics and the catalytic behaviour of the resulted catalysts.     

Molecular Dynamics Simulation of the Crystallizable Fragment of IgG1—Insights for the Design of Fcabs

An interesting format in the development of therapeutic monoclonal antibodies uses the crystallizable fragment of IgG1 as starting scaffold. Engineering of its structural loops allows generation of an antigen binding site. However, this might impair the molecule’s conformational stability, which can be overcome by introducing stabilizing point mutations in the CH3 domains. These point mutations often affect the stability and unfolding behavior of both the CH2 and CH3 domains. In order to understand this cross-talk, molecular dynamics simulations of the domains of the Fc fragment of human IgG1 are reported. The structure of human IgG1-Fc obtained from X-ray crystallography is used as a starting point for simulations of the wild-type protein at two different pH values. The stabilizing effect of a single point mutation in the CH3 domain as well as the impact of the hinge region and the glycan tree structure connected to the CH2 domains is investigated. Regions of high local flexibility were identified as potential sites for engineering antigen binding sites. Obtained data are discussed with respect to the available X-ray structure of IgG1-Fc, directed evolution approaches that screen for stability and use of the scaffold IgG1-Fc in the design of antigen binding Fc proteins.     

Structure and Function of the Catalyst and the Promoter in Co—Mo Hydrodesulfurization Catalysts

Simply stated, a membrane is a barrier which is capable of redistributing components in a fluid stream through a driving force such as the difference in pressure, concentration, or electrical potential. When a concentration or electrical potential gradient provides the necessary driving force, this barrier separation process is called dialysis or electrodialysis. Most of the membrane processes are based on an applied pressure difference across the membranes.     

Role of the Initial Formation of the Iron Nano-Particles in the Multi-Walled Carbon Nanotubes Growth Process

Careful preparation of the iron nano-particle catalyst for carbon nanotubes (CNTs) fabrication has crucial importance for initial growth of multi-wall carbon-nanotubes (MWCNTs). Thin iron layer was thermally deposited in a high vacuum onto the surface of the SiO2/Si wafer at about 300 K. The sample was heated up to 700℃ in a hydrogen atmosphere, and then the sample was heated once again at750℃ in ethylene atmosphere. After hydrogen treatment continuous Fe layer was changed into many well separated Fe nano-peaks. AFM, SEM and HR-TEM studies of deposited MWCNTs allow us to propose a growth mechanism for long, straight MWCNTs.     

Offspring Number Does Not Influence Reaching the Disability’s Milestones in Multiple Sclerosis: A Seven-Year Follow-Up Study

Objectives: data on pregnancy long-term effects on multiple sclerosis (MS) course are still controversial; whether experiencing more than one pregnancy exposes one to risk of the disability‘s accrual is still unknown. We investigated differences existing in terms of disability progression among women with MS (wwMS) who had one or more children after their MS onset. Methods: Monoparous and multiparous wwMS were enrolled from the Catania MS Center, Italy, in a monocenter retrospective study. A Cox proportional hazards model was used to examine the effect of the number of parities on time from MS disease onset to EDSS 4.0 and 6.0. The study protocol was approved by the local Ethical Committee. Results: during the seven years of observation, 32.1% and 23.2% of the monoparous group reached expanded disability disease status (EDSS) 4.0 and 6.0 respectively, compared to 13.3% and 3.3% of the multiparous group (p = 0.057 and p = 0.017; respectively). The Kaplan–Meier curve analysis showed no statistically-significant differences between the two groups in reaching the two milestones. The multiparous group showed a longer time to reach the EDSS 4.0 (3.5 vs. 2.6 years, log-rank 0.57, p = 0.45). The Cox regression analysis showed that the EDSS at the time of first pregnancy (Exp(B) 9.4, CI 4.5–19.7, p < 0.001) and the time from MS onset to first pregnancy (Exp(B) 0.96, CI = 0.93–0.98, p < 0.05) were significant predictors of reaching the EDSS 4.0, whereas a model including only the EDSS one year after the first pregnancy significantly predicted (Exp(B) value of 6.4, CI 2.6–15.4, p < 0.001) the reaching of EDSS 6.0. Conclusions: Our results suggest that experiencing more than one pregnancy could not convey a different clinical outcome in wwMS. Further research is needed to confirm our results.     

New energy and new power – the prospect of increasing use of polymers in fuel cells

Researching on fuel cells is an important direction of developing new energy in the twenty-first century. Fuel cells present broad application in the aerospace, military, power stations, electric vehicles and portable power applications due to their high power conversion efficiency (40–60%), environmental friendliness and reliability, small size, low noise and so on. This review gives an introduction into the fundamental, characteristics and applications of various fuel cells. In addition, the development of increasing use of polymers in fuel cells is also prospected.     

New fields of application of materials and articles from refractory fibers in the Al2O3 — SiO2 system

Basic properties of materials and articles from refractory fibers that save resources, cut heat loss, and reduce the consumption of material for furnaces are presented. A new direction in the development of materials and articles from refractory fibers for converter production is described