Nephrocytes Remove Microbiota-Derived Peptidoglycan from Systemic Circulation to Maintain Immune Homeostasis.

Preventing aberrant immune responses against the microbiota is essential for the health of the host. Microbiota-shed pathogen-associated molecular patterns translocate from the gut lumen into systemic circulation. Here, we examined the role of hemolymph (insect blood) filtration in regulating systemic responses to microbiota-derived peptidoglycan. Drosophila deficient for the transcription factor Klf15 (Klf15NN) are viable but lack nephrocytes-cells structurally and functionally homologous to the glomerular podocytes of the kidney. We found that Klf15NN flies were more resistant to infection than wild-type (WT) counterparts but exhibited a shortened lifespan. This was associated with constitutive Toll pathway activation triggered by excess peptidoglycan circulating in Klf15NN flies. In WT flies, peptidoglycan was removed from systemic circulation by nephrocytes through endocytosis and subsequent lysosomal degradation. Thus, renal filtration of microbiota-derived peptidoglycan maintains immune homeostasis in Drosophila, a function likely conserved in mammals and potentially relevant to the chronic immune activation seen in settings of impaired blood filtration.

Cytokine Blood Filtration Responses in COVID-19.

The real issue with the COVID-19 pandemic is that a rapidly increasing number of patients with life-threatening complications are admitted in hospitals and are not well-administered. Although a limited number of patients use the intensive care unit (ICU), they consume medical resources, safety equipment, and enormous equipment with little possibility of rapid recovery and ICU discharge. This work reviews effective methods of using filtration devices in treatment to reduce the level of various inflammatory mediators and discharge patients from the ICU faster. Extracorporeal technologies have been reviewed as a medical approach to absorb cytokines. Although these devices do not kill or remove the virus, they are a promising solution for treating patients and their faster removal from the ICU, thus relieving the bottleneck.

Impact of blood manufacturing and donor characteristics on membrane water permeability and in vitro quality parameters during hypothermic storage of red blood cells.

Several factors have been proposed to influence the red blood cell storage lesion including storage duration, blood component manufacturing methodology, and donor characteristics [1,18]. The objectives of this study were to determine the impact of manufacturing method and donor characteristics on water permeability and membrane quality parameters. Red blood cell units were obtained from volunteer blood donors and grouped according to the manufacturing method and donor characteristics of sex and age. Membrane water permeability and membrane quality parameters, including deformability, hemolysis, osmotic fragility, hematologic indices, supernatant potassium, and supernatant sodium, were determined on day 5 ±â€¯2, day 21, and day 42. Regression analysis was applied to evaluate the contribution of storage duration, manufacturing method, and donor characteristics on storage lesion. This study found that units processed using a whole blood filtration manufacturing method exhibited significantly higher membrane water permeability throughout storage compared to units manufactured using red cell filtration. Additionally, significant differences in hemolysis, supernatant potassium, and supernatant sodium were seen between manufacturing methods, however there were no significance differences between donor age and sex groups. Findings of this study suggest that the membrane-related storage lesion is initiated prior to the first day of storage with contributions by both blood manufacturing process and donor variability. The findings of this work highlight the importance of characterizing membrane water permeability during storage as it can be a predictor of the biophysical and chemical changes that affect the quality of stored red blood cells during hypothermic storage.

Assessing the influence of component processing and donor characteristics on quality of red cell concentrates using quality control data.

BACKGROUND AND OBJECTIVES: Quality control (QC) data collected by blood services are used to monitor production and to ensure compliance with regulatory standards. We demonstrate how analysis of quality control data can be used to highlight the sources of variability within red cell concentrates (RCCs). MATERIALS AND METHODS: We merged Canadian Blood Services QC data with manufacturing and donor records for 28 227 RCC between June 2011 and October 2014. Units were categorized based on processing method, bag manufacturer, donor age and donor sex, then assessed based on product characteristics: haemolysis and haemoglobin levels, unit volume, leucocyte count and haematocrit. RESULTS: Buffy-coat method (top/bottom)-processed units exhibited lower haemolysis than units processed using the whole-blood filtration method (top/top). Units from female donors exhibited lower haemolysis than male donations. Processing method influenced unit volume and the ratio of additive solution to residual plasma. CONCLUSIONS: Stored red blood cell characteristics are influenced by prestorage processing and donor factors. Understanding the relationship between processing, donors and RCC quality will help blood services to ensure the safety of transfused products.

Determining the Volume of Additive Solution and Residual Plasma in Whole Blood Filtered and Buffy Coat Processed Red Cell Concentrates.

BACKGROUND: Residual plasma in transfused red cell concentrates (RCCs) has been associated with adverse transfusion outcomes. Despite this, there is no consensus on the standard procedure for measuring residual plasma volume. METHODS: The volumes of residual plasma and additive solution were measured in RCCs processed using two separation methods: whole blood filtration (WBF) and buffy coat (BC)/RCC filtration. The concentration of mannitol and albumin in RCC components was measured using colorimetric assays. Mannitol concentration was used to calculate additive solution volume. Residual plasma volume was calculated using two methods. RESULTS: Calculated RCC supernatant volumes were much lower in BC-processed components compared to WBF-processed components (BC = 97 ± 6 ml, WBF = 109 ± 4 ml; p < 0.05). Calculated additive solution volumes were greater in WBF- than in BC-processed components (BC = 81 ± 4 ml, WBF = 105 ± 2 ml; p < 0.05). Absolute residual plasma volume varied significantly based on the calculation method used. CONCLUSION: Disparity between plasma volume calculation methods was observed. Efforts should be made to standardize residual plasma volume measurement methods in order to accurately assess the impact of residual plasma on transfusion outcomes.

Contribution of peripheral blood mononuclear cells isolated by advanced filtration system to myogenesis of human bone marrow mesenchymal stem cells co-cultured with myoblasts.

Background: Contribution of peripheral blood mononuclear cells (PBMCs) in myogenesis is still under debate, even though blood filtration systems are commonly used in clinical practice for successfully management of critic limb ischemia. Objectives: A commercial blood filter used for autologous human PBMC transplantation procedures is characterized and used to collect PBMCs, that are then added to well-established 2D in vitro myogenic models assembled with a co-culture of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) and skeletal myoblasts (hSkMs) whit the aim of investigating their potential contribution to stem cell myogenic commitment. Methods: A commercial blood filter was physically and chemically studied to understand its morphological characteristics and composition. PBMCs were concentrated using this system, further isolated by Ficoll-Paque density gradient centrifugation, and then added in an upper transwell chamber to a 2D co-culture of hBM-MSCs and hSkMs. Myogenic commitment was investigated by RT-PCR, immunofluorescence, and flow cytometry immunophenotyping. Cytokine levels were monitored by ELISA assay in culture media. Results: The blood filtration system was disassembled and appeared to be formed by twelve membranes of poly-butylene terephthalate fibers (diameters, 0.9-4.0 µm) with pore size distribution of 1-20 µm. Filter functional characterization was achieved by characterizing collected cells by flow cytometry. Subsequently, collected PBMCs fraction was added to an in-vitro model of hBM-MSC myogenic commitment. In the presence of PBMCs, stem cells significantly upregulated myogenic genes, such as Desmin and MYH2, as confirmed by qRT-PCR and expressed related proteins by immunofluorescence (IF) assay, while downregulated pro-inflammatory cytokines (IL12A at day 14) along the 21 days of culture. Novelty: Our work highlights chemical-physical properties of commercial blood filter and suggests that blood filtrated fraction of PBMC might modulate cytokine expression in response to muscle injury and promote myogenic events, supporting their clinical use in autologous transplantation.

Roll-to-Roll Manufacturing of Integrated Immunodetection Sensors.

Lack of functional integration and high manufacturing costs have been identified as major challenges in commercialization of point-of-care devices. In this study, roll-to-roll (R2R) fabrication process was developed for large-scale manufacturing of disposable microfluidic devices. The integrated, user-friendly device included a plasma separation membrane for simple blood filtration, immobilized antibodies for specific immunodetection, microfluidics for plasma transport and reagent mixing, and a blister for actuation and waste storage. These functionalities were designed to be compatible with R2R processing, which was demonstrated using pilot-scale printing lines producing 60 devices in an hour. The produced sensors enabled rapid (10 min) and sensitive (2 µg/mL) fluorescence-based immunodetection of C-reactive protein from 20 µL of whole blood.

A Technology Roadmap for Innovative Approaches to Kidney Replacement Therapies: A Catalyst for Change.

The number of patients dialyzed for ESKD exceeds 500,000 in the United States and more than 2.6 million people worldwide, with the expectation that the worldwide number will double by 2030. The human cost of health and societal financial cost of ESKD is substantial. Dialytic therapy is associated with an unacceptably high morbidity and mortality rate and poor quality of life. Although innovation in many areas of science has been transformative, there has been little innovation in dialysis or alternatives for kidney replacement therapy (KRT) since its introduction approximately 70 years ago. Advances in kidney biology, stem cells and kidney cell differentiation protocols, biomaterials, sensors, nano/microtechnology, sorbents and engineering, and interdisciplinary approaches and collaborations can lead to disruptive innovation. The Kidney Health Initiative, a public-private partnership between the American Society of Nephrology and the US Food and Drug Administration, has convened a multidisciplinary group to create a technology roadmap for innovative approaches to KRT to address patients' needs. The Roadmap is a living document. It identifies the design criteria that must be considered to replace the myriad functions of the kidney, as well as scientific, technical, regulatory, and payor milestones required to commercialize and provide patient access to KRT alternatives. Various embodiments of potential solutions are discussed, but the Roadmap is agnostic to any particular solution set. System enablers are identified, including vascular access, biomaterial development, biologic and immunologic modulation, function, and safety monitoring. Important Roadmap supporting activities include regulatory alignment and innovative financial incentives and payment pathways. The Roadmap provides estimated timelines for replacement of specific kidney functions so that approaches can be conceptualized in ways that are actionable and attract talented innovators from multiple disciplines. The Roadmap has been used to guide the selection of KidneyX prizes for innovation in KRT.

Zwitterionic fibrous polypropylene assembled with amphiphatic carboxybetaine copolymers for hemocompatible blood filtration.

UNLABELLED: The present study serves three main functions. First, it presents a novel random copolymer, made of octadecyl acrylate hydrophobic blocks and 2-(dimethylamino)ethyl methacrylate hydrophilic groups, and it zwitterionic form. Second, random copolymer and zwitterionic random copolymer, OmDn and Z-OmDn, are used to modify polypropylene membranes by evaporation coating. Our investigations unveil that this method leads to sufficiently stable self-assembling provided a minimum number of hydrophobic repeat units of 77, which also corresponds to a hydrophobic degree of 74%. Third, antifouling and hemocompatible properties of membranes are thoroughly investigated using all types of blood cells separately, as well as challenging membranes against whole blood in static and dynamic conditions. Membranes modified with zwitterionic copolymer containing 26% of zwitterionic groups are shown to be highly antifouling and hemocompatible, for a coating density as low as 0.2mg/cm(2). Their application in a specially designed blood filtration module enabled to almost totally inhibit blood cells interactions with membrane material, as well as to importantly reduce platelet activation in the permeate (2.5-fold reduction). STATEMENT OF SIGNIFICANCE: The design of new zwitterionic copolymer material is proposed and demonstrated in this study. It was showed that hydrophobicoctadecyl acrylate segments can be introduced in the zwitterioniccarboxybetaine polymer chain with a well-controlled random sequence. Stable, efficient, and effective surface zwitterionization of hydrophobic polypropylene are obtained via grafting onto approach by evaporation-induced self-assembling coating. In the perspective of potential application, hemocompatible blood filtration was demonstrated with the excellent results of non-activated platelets obtained. DESIGN: New zwitterionicmaterial, amphiphatic carboxybetaine copolymers. DEVELOPMENT: Evaporation-induced self-assembling grafting. APPLICATION: Hemocompatible blood filtration.

Antiaging therapy: a prospective hypothesis.

This hypothesis proposes a new prospective approach to slow the aging process in older humans. The hypothesis could lead to developing new treatments for age-related illnesses and help humans to live longer. This hypothesis has no previous documentation in scientific media and has no protocol. Scientists have presented evidence that systemic aging is influenced by peculiar molecules in the blood. Researchers at Albert Einstein College of Medicine, New York, and Harvard University in Cambridge discovered elevated titer of aging-related molecules (ARMs) in blood, which trigger cascade of aging process in mice; they also indicated that the process can be reduced or even reversed. By inhibiting the production of ARMs, they could reduce age-related cognitive and physical declines. The present hypothesis offers a new approach to translate these findings into medical treatment: extracorporeal adjustment of ARMs would lead to slower rates of aging. A prospective "antiaging blood filtration column" (AABFC) is a nanotechnological device that would fulfill the central role in this approach. An AABFC would set a near-youth homeostatic titer of ARMs in the blood. In this regard, the AABFC immobilizes ARMs from the blood while blood passes through the column. The AABFC harbors antibodies against ARMs. ARM antibodies would be conjugated irreversibly to ARMs on contact surfaces of the reaction platforms inside the AABFC till near-youth homeostasis is attained. The treatment is performed with the aid of a blood-circulating pump. Similar to a renal dialysis machine, blood would circulate from the body to the AABFC and from there back to the body in a closed circuit until ARMs were sufficiently depleted from the blood. The optimal application criteria, such as human age for implementation, frequency of treatments, dosage, ideal homeostasis, and similar concerns, should be revealed by appropriate investigations. If AABFC technology undergoes practical evaluations and gains approval, it would hold future promises such as: 1) prolonged lifespans; 2) slowed age-related illnesses such as low bone mass, weak muscular systems, diabetes, arthritis, Alzheimer's disease, and impaired memory in the elderly; 3) reduced health expenses; 4) reduced cosmetic surgeries performed on the elderly; 5) healthier astronauts in extended outer space journeys; 6) reduced financial burden of advanced care for the elderly imposed upon both government and society; and 7) rejuvenating effects in healthy, non-aged individuals.

Clinical analysis of continuous blood filtration combined with naloxone in treatment of PICU multiple organ dysfunction syndrome / 中国生化药物杂志

Objective To investigate clinical effect of patients with PICU multiple organ dysfunction by continuous blood filtration combined with naloxone.Methods 42 patients with multiple organ function failure were selected and randomly divided into 2 groups.The control group were treated by PICU conventional therapy, the experiment group were treated by continuous blood filtration combined with Naloxone.Vital signs, creatinine, creatine kinase and aspartate aminotransferase levels, length of stay and blood filtration were compared after 1 day and 3 days treatment.ResuIts Compared with control group,heart rate, oxidation index,creatinine and aspartate aminotransferase levels of the experiment group were lower(P<0.05).After 1 day and 3 days, compared with cnontrol group, length of stay and blood filtration of the experiment were lower(P<0.05).ConcIusion Continuous blood filtration combined with naloxone in treatment of multiple organ dysfunction syndrome PICU is effective and reliable.It can significantly improve renal function, shorten the length of hospital stay, and remove inflammatory mediators in plasma of patients.

To evaluate the clearance of cytokines by the technique of continuos filtration of blood in patients suffering from severe intoxicated infected burn

71 patients with severe burns, who had had various organ dysfunction were divided randomly into 2 groups: one underwent continuous veno-venous hemofiltration (CVVH), and the other was control group. Results showed a significant decrease of plasma level of cytokine, including IL2, IL6, IL8 and TNF after CVVH (p<0.01). In addition, mortality rate of CVVH group accounted for 38.71%, considerably lower than those of the control group