Therapeutic Plasma Exchange in Certain Immune-Mediated Neurological Disorders: Focus on a Novel Nanomembrane-Based Technology

Therapeutic plasma exchange (TPE) is an efficient extracorporeal blood purification technique to remove circulating autoantibodies and other pathogenic substances. Its mechanism of action in immune-mediated neurological disorders includes immediate intravascular reduction of autoantibody concentration, pulsed induction of antibody redistribution, and subsequent immunomodulatory changes. Conventional TPE with 1 to 1.5 total plasma volume (TPV) exchange is a well-established treatment in Guillain-Barre Syndrome, Chronic Inflammatory Demyelinating Polyradiculoneuropathy, Neuromyelitis Optica Spectrum Disorder, Myasthenia Gravis and Multiple Sclerosis. There is insufficient evidence for the efficacy of so-called low volume plasma exchange (LVPE) (<1 TPV exchange) implemented either by the conventional or by a novel nanomembrane-based TPE in these neurological conditions, including their impact on conductivity and neuroregenerative recovery. In this narrative review, we focus on the role of nanomembrane-based technology as an alternative LVPE treatment option in these neurological conditions. Nanomembrane-based technology is a promising type of TPE, which seems to share the basic advantages of the conventional one, but probably with fewer adverse effects. It could play a valuable role in patient management by ameliorating neurological symptoms, improving disability, and reducing oxidative stress in a cost-effective way. Further research is needed to identify which patients benefit most from this novel TPE technology

Therapeutic Plasma Exchange in Certain Immune-Mediated Neurological Disorders: Focus on a Novel Nanomembrane-Based Technology

Therapeutic plasma exchange (TPE) is an efficient extracorporeal blood purification technique to remove circulating autoantibodies and other pathogenic substances. Its mechanism of action in immune-mediated neurological disorders includes immediate intravascular reduction of autoantibody concentration, pulsed induction of antibody redistribution, and subsequent immunomodulatory changes. Conventional TPE with 1 to 1.5 total plasma volume (TPV) exchange is a well-established treatment in Guillain-Barre Syndrome, Chronic Inflammatory Demyelinating Polyradiculoneuropathy, Neuromyelitis Optica Spectrum Disorder, Myasthenia Gravis and Multiple Sclerosis. There is insufficient evidence for the efficacy of so-called low volume plasma exchange (LVPE) (<1 TPV exchange) implemented either by the conventional or by a novel nanomembrane-based TPE in these neurological conditions, including their impact on conductivity and neuroregenerative recovery. In this narrative review, we focus on the role of nanomembrane-based technology as an alternative LVPE treatment option in these neurological conditions. Nanomembrane-based technology is a promising type of TPE, which seems to share the basic advantages of the conventional one, but probably with fewer adverse effects. It could play a valuable role in patient management by ameliorating neurological symptoms, improving disability, and reducing oxidative stress in a cost-effective way. Further research is needed to identify which patients benefit most from this novel TPE technology

Aging, partial reprogramming and bioelectric fields: unveiling the path to cellular rejuvenation

The studies of rejuvenation are important for promoting health and longevity, preventing age-related diseases, reducing economic burdens, improving quality of life and addressing the challenges posed by an aging global population. This review explores the intersection of aging, regeneration and bioelectric fields examining the emerging role of membrane potential in processes like cell proliferation, differentiation, limb regeneration and potentially aging. Manipulation of membrane potential opens a novel dimension to the rejuvenation landscape offering an alternative or complementary approach to partial reprograming method presenting exciting possibilities for therapeutic interventions targeting age-related cellular changes

Of mice and men – differential mechanisms of maintaining the undifferentiated state in mESC and hESC

The persistence of the defining characteristics of undifferentiated cells in vivo and in vitro is maintained via a complex interplay of several mechanisms, employing molecular events internal to the cell as well as signals originating outside the cell. The exogenous and the endogenous mechanisms maintaining stemness qualities of the cell are intricately interwoven with one another and susceptible to cross-interference. Mice and rats as animal models are almost universally considered to be close enough to humans so as to be used in research and applications eventually intended for use in human biology and medicine, at the same time being related distantly enough from primates so as not to overstep ethical boundaries. Studying the specific molecular features of both species in the context of maintenance of the undifferentiated state of mESC and hESC can provide researchers with an unique opportunity to unravel the network of interactions which take part in the decision about cell fate under different conditions; to glean interesting insights into the parallel evolution of the two species and to observe how different variants of basic cellular processes have been tried and tested in the evolutionary process. The present paper reviews the basic signalling pathways responsible for the maintenance of the undifferentiated state in mESC and hESC and analyses some specific aspects of the molecular physiology that are unique to the particular species

Of mice and men – differential mechanisms of maintaining the undifferentiated state in mESC and hESC

The persistence of the defining characteristics of undifferentiated cells in vivo and in vitro is maintained via a complex interplay of several mechanisms, employing molecular events internal to the cell as well as signals originating outside the cell. The exogenous and the endogenous mechanisms maintaining stemness qualities of the cell are intricately interwoven with one another and susceptible to cross-interference. Mice and rats as animal models are almost universally considered to be close enough to humans so as to be used in research and applications eventually intended for use in human biology and medicine, at the same time being related distantly enough from primates so as not to overstep ethical boundaries. Studying the specific molecular features of both species in the context of maintenance of the undifferentiated state of mESC and hESC can provide researchers with an unique opportunity to unravel the network of interactions which take part in the decision about cell fate under different conditions; to glean interesting insights into the parallel evolution of the two species and to observe how different variants of basic cellular processes have been tried and tested in the evolutionary process. The present paper reviews the basic signalling pathways responsible for the maintenance of the undifferentiated state in mESC and hESC and analyses some specific aspects of the molecular physiology that are unique to the particular species

Metabolic Profiling of Xylooligosaccharides by Lactobacilli

Three lactic acid bacteria (LAB) strains identified as Lactobacillus plantarum, Lactobacillus brevis, and Lactobacillus sakei isolated from meat products were tested for their ability to utilize and grow on xylooligosaccharides (XOSs). The extent of carbohydrate utilization by the studied strains was analyzed by HPLC. All three strains showed preferences for the degree of polymerization (DP). The added oligosaccharides induced the LAB to form end-products of typical mixed-acid fermentation. The utilization of XOSs by the microorganisms requires the action of three important enzymes: &beta;-xylosidase (EC 3.2.1.37) exo-oligoxylanase (EC 3.2.1.156) and &alpha;-L-arabinofuranosidase (EC 3.2.1.55). The presence of intracellular &beta;-D-xylosidase in Lb. brevis, Lb. plantarum, and Lb. sakei suggest that XOSs might be the first imported into the cell by oligosaccharide transporters, followed by their degradation to xylose. The studies on the influence of XOS intake on the lipids of rat liver plasma membranes showed that oligosaccharides display various beneficial effects for the host organism, which are probably specific for each type of prebiotic used. The utilization of different types of oligosaccharides may help to explain the ability of Lactobacillus strains to compete with other bacteria in the ecosystem of the human gastrointestinal tract

Ceramides increase the activity of the secretory phospholipase A2 and alter its fatty acid specificity.

Modulation of human recombinant secretory type II phospholipase A(2) activity by ceramide and cholesterol was investigated using model glycerophospholipid substrates composed of phosphatidylethanolamine and phosphatidylserine dispersed in aqueous medium. Enzyme activity was monitored by measurement of released fatty acids using capillary GC-MS. Fatty acids from the sn-2 position of the phospholipids were hydrolysed by the enzyme in proportion to the relative abundance of the phospholipid in the substrate. Addition of increasing amounts of ceramide to the substrate progressively enhanced phospholipase activity. The increased activity was accomplished largely by preferential hydrolysis of polyunsaturated fatty acids, particularly arachidonic acid, derived from phosphatidylethanolamine. The addition of sphingomyelin to the substrate glycerophospholipids inhibited phospholipase activity but its progressive substitution by ceramide, so as to mimic sphingomyelinase activity, counteracted the inhibition. The presence of cholesterol in dispersions of glycerophospholipid-substrate-containing ceramides suppressed activation of the enzyme resulting from the presence of ceramide. The molecular basis of enzyme modulation was investigated by analysis of the phase structure of the dispersed lipid substrate during temperature scans from 46 to 20 degrees C using small-angle synchrotron X-ray diffraction. These studies indicated that intermediate structures created after ceramide-dependent phase separation of hexagonal and lamellar phases represent the most susceptible form of the substrate for enzyme hydrolysis

Hyperglycemia attenuates fibroblast contractility via suppression of TβRII receptor modulated α-smooth muscle actin expression

AbstractNonhealing wounds are a common complication in patients suffering from diabetes with hyperglycemia being the most deteriorating factor for this serious pathological condition. Despite the great body of data, the molecular mechanisms by which high glucose affects cellular physiology are still poorly defined. Here we used primary human foreskin fibroblasts cultured in normo- and hyperglycemic conditions to study the mechanisms leading to altered cell contractility. Our results demonstrated that 25 mmol/L glucose effectively reduced fibroblasts ability to contract fibrin gels, and this physiological change was accompanied by a decrease in alpha-smooth muscle actin expression and the percentage of spontaneously differentiated myofibroblasts in the population of high glucose-treated fibroblasts. These changes were a result of hyperglycemia-induced attenuation of TGF-β1 signaling, involving specific suppression of TGF-β receptor type II but not type I expression. Decreased production of the receptor abolished the ability of exogenously added TGF-β1 to induce Smad2/3 phosphorylation in the presence of high glucose concentrations. Our results identify TGF-β receptor type II as hyperglycemia expression-sensitive receptor and add further aspect to the complex way in which high glucose can affect the wound healing process