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Background: The angiotensin-converting enzyme (ACE) metabolizes a number of important peptides participating in blood pressure regulation and vascular remodeling. Elevated blood ACE is a marker for granulomatous diseases and elevated ACE expression in tissues is associated with increased risk of cardiovascular diseases. Objective and Methodology: We applied a novel approach —ACE phenotyping—to find a reason for conformationally impaired ACE in the blood of one particular donor. Similar conformationally altered ACEs were detected previously in 2–4% of the healthy population and in up to 20% of patients with uremia, and were characterized by significant increase in the rate of angiotensin I hydrolysis. Principal findings: This donor has (1) significantly increased level of endogenous ACE inhibitor in plasma with MW less than 1000; (2) increased activity toward angiotensin I; (3) M71V mutation in ABCG2 (membrane transporter for more than 200 compounds, including bilirubin). We hypothesize that this patient may also have the decreased level of free bilirubin in plasma, which normally binds to the N domain of ACE. Analysis of the local conformation of ACE in plasma of patients with Gilbert and Crigler-Najjar syndromes allowed us to speculate that binding of mAbs 1G12 and 6A12 to plasma ACE could be a natural sensor for estimation of free bilirubin level in plasma. Totally, 235 human plasma/sera samples were screened for conformational changes in soluble ACE. Conclusions/Significance: ACE phenotyping of plasma samples allows us to identify individuals with conformationally altered ACE. This type of screening has clinical significance because this conformationally altered ACE could not only result in the enhancement of the level of angiotensin II but could also serve as an indicator of free bilirubin levels. [ABSTRACT FROM AUTHOR]

Simple Summary: Human papillomavirus (HPV) is connected with virtually all cases of cervical cancer. The viral infection-associated chronic inflammation, oxidative stress, and alterations in apoptosis have been considered as leading risk factors for carcinogenesis in humans. In an observational clinical study, we identified oxidative markers and the cervical/circulating ligands of TNF-alpha-induced apoptosis involved in HPV-associated cervical carcinogenesis. In the following clinical trial, 250 females infected with high-cancer-risk HPV16/18 (healthy and pre-cancerous) were recruited into a placebo-controlled clinical study of supplementation with fermented mangosteen (FM, 28g/day, daily) for three months. Our findings indicate that FM, and not a placebo, in combination with routine anti-viral therapy, could prevent, slow down, or even interrupt HPV-associated cervical carcinogenesis, mainly through the suppression of leukocyte recruitment into infected tissue, through anti-inflammatory effects, and through the restoration of nitric oxide metabolite-initiated TRAIL-dependent apoptosis. In the observational clinical study, we identified the oxidative markers of HPV-associated cervical carcinogenesis and the local/circulating ligands of TNF-alpha-induced apoptosis. Cervical biopsies of 196 females infected with low-cancer-risk HPV10/13 or high-cancer-risk HPV16/18 (healthy, pre-cancerous CIN I and CIN II, and CIN III carcinoma) were analysed for OH radical scavenging, catalase, GSH-peroxidase, myeloperoxidase (MPO), nitrate/nitrite, nitrotyrosine, and isoprostane. Ligands of TNF-alpha-dependent apoptosis (TNF-alpha, TRAIL, IL-2, and sFAS) were determined in cervical fluid, biopsies, and serum. Cervical MPO was highly enhanced, while nitrotyrosine decreased in CIN III. Local/circulating TRAIL was remarkably decreased, and higher-than-control serum TNF-alpha and IL-2 levels were found in the CIN I and CIN III groups. Then, 250 females infected with HPV16/18 (healthy and with CIN I and CIN II) were recruited into a placebo-controlled clinical study of supplementation with fermented mangosteen (FM, 28g/day, daily) for three months. Post-trial colposcopy revealed normal patterns in 100% of the FM group versus 62% of the placebo group. Inflammatory cells in cervical fluid were found in 21% of the FM group versus 40% of the placebo group. Locally, FM drastically diminished MPO and NO2/NO3, while it remarkably increased TRAIL. Additionally, FM supplementation normalised serum TRAIL, TNF-alpha, and IL-2. [ABSTRACT FROM AUTHOR]

Background and Objectives: Implementation of the technique of immunomagnetic selection requires the procurement of a large number of CD34+ cells from haploidentical donors within a single apheresis procedure. The release of stem cells with granulocyte colony‐stimulating factor (G‐CSF) alone is unsatisfactory in a number of donors, and plerixafor, a CXCR4 chemokine receptor antagonist, could be used as an additional mobilization agent. The aim of our study was to examine whether a lower dose of plerixafor (0.12 mg/kg) can provide sufficient increase in CD34+ cells in the peripheral blood of allogeneic healthy donors in comparison with a historical control group. In addition, we assessed the risk of inability to provide the recipient with a transplant containing the optimal dose of 8–10 × 106 CD34+ cells/kg body weight of the recipient. Materials and Methods: In a prospective, single‐arm study, we examined the results of 105 mobilizations in healthy adult haploidentical donors with G‐CSF and plerixafor at a dose of 0.12 mg/kg. The historical control group consisted of 106 mobilizations with G‐CSF and plerixafor at 0.24 mg/kg. Results: The median increase in the number of CD34+ cells from day 4 to day 5 of mobilization was 69 cells/μl (range, 28–240) versus 77 cells/μl (24–217) in the groups of 0.12 and 0.24 mg/kg of plerixafor, respectively (p‐value 0.255). The apheresis products contained a median of 14.4 × 106/kg recipient body weight CD34+ cells versus 12.9 × 106/kg in the groups that received 0.12 and 0.24 mg/kg of plerixafor, respectively (p‐value 0.118). The obtained differences were not significant, which means the application of a decreased dose of plerixafor did not affect the results of mobilization. Conclusion: The obtained differences in collection were not significant, and thus the application of a decreased dose of plerixafor did not affect the results of mobilization. [ABSTRACT FROM AUTHOR]

Food supplements based on fermented Carica papaya and Morinda citrifolia, known for their immune modulating, redox balancing, and anti-inflammatory effects, were added to conventional treatment protocols prescribed to patients recovering after severe and moderate COVID-19 disease in order to alleviate long-lasting post-COVID symptoms. A randomized single-center placebo-controlled clinical laboratory study was designed and performed (total number of participants 188, with delta variant of virus 157, with omicron 31). Clinical statuses were assessed using computer tomography, electrocardiography, a questionnaire, and physical endurance. Plasma cytokines (IL-6, IL-8, IL-17A, and INF-gamma), nitrate/nitrite ratio, antioxidant activity (AOA), and polymorphonuclear leukocyte (PMN) ATP levels were determined before and 20 days following the addition of 28 g of fermented supplements twice per day. The capacity of PMN to phagocyte and the oral-nasal-pharyngeal microbiota were assessed. Clinical symptoms, IL-6, IL-8, and nitric oxide metabolites diminished significantly compared to the placebo group and their background expression. The PMN capacity to phagocyte, AOA, and ATP content remarkably increased. The oral-nasal-pharyngeal microbiota were unchanged. On these grounds, we suggest that fermented tropical fruits could efficiently diminish post-COVID clinical symptoms through several immune-modulating, redox balancing, and pro-energy mechanisms. [ABSTRACT FROM AUTHOR]

Background: Collection of a large number of early hematopoietic progenitors is essential for allogeneic apheresis products intended for TCR‐alpha/beta depletion. Materials and Methods: We added plerixafor 0.24 mg/kg body weight (bw) on day 4 of high‐dose filgrastim mobilization 10 hours prior to apheresis in 16 (30.5%) pediatric allogeneic donors who failed to recover a sufficient number of CD34+ cells. Results: On day 4 of G‐CSF, the median CD34+ cell count in peripheral blood was 6 per μL (range 4‐9 per μL) in 6 poor mobilizers and 16 per μL (range 12‐19 per μL) in insufficient mobilizers. In all donors, the threshold of 50 CD34+ cells/μL was achieved, and the median increase was 14.8‐fold in poor mobilizers and 6.5‐fold in insufficient mobilizers, whereas it was 3.45‐fold increase in those mobilized with G‐CSF alone. Discussion: In all donors, a predefined number of >10 × 106 CD34+ cells/kg of recipient bw before depletion was reached in the apheresis product. The use of plerixafor did not affect the purity of further TCR‐alpha/beta depletion. Side effects were mild to moderate and consisted of nausea and vomiting. Conclusion: Thus, the safety and high efficacy of plerixafor was proven in healthy pediatric allogeneic hematopoietic cell donors. [ABSTRACT FROM AUTHOR]

Background: We used laboratory indicators to evaluate the quality of pathogen‐reduced red blood cell suspension (RBCS) compared with gamma‐irradiated RBCS. Materials and methods: To determine biochemical and metabolic parameters of RBCS, we obtained 50 whole blood units from healthy volunteers and randomized them into 2 groups: 25 were pathogen‐reduced, and then, RBCS prepared from them. RBCS from the other 25 was gamma‐irradiated. Sampling was carried out on day zero before and after treatment and at 7, 14, 21 and 28 days. To determine lymphocyte inactivation, we collected another 35 whole blood units. Each was sampled to form 3 study groups: untreated, gamma‐irradiated and pathogen‐reduced. Daily sampling was carried out during 3 days of storage. Results: The quality of RBCS from both groups was largely the same, except for haemolysis and red blood cell fragility, which were more pronounced in the pathogen‐reduced group. This finding limited the shelf life of pathogen‐reduced RBCS to 14 days. Lymphocyte viability was significantly reduced after both treatments. Proliferation of lymphocytes after pathogen reduction was reduced to the detection limit, while low‐level proliferation was observed in gamma‐irradiated samples. Conclusion: Pathogen‐reduced red blood cells have acceptable quality and can be used for transfusion within 14 days. Results of inactivation of lymphocytes demonstrate that pathogen reduction technology, applied on WB, can serve as an alternative to irradiation. [ABSTRACT FROM AUTHOR]

The article offers information on the Vox Sanguinis International Forum on paediatric indications for blood component transfusion. Topics discussed include information on the hospital and transfusion service demographics; discussions on the transfusion Indications for paediatric and neonatal patients; and the information on the product manipulations for paediatric and neonatal patients.

Background: Transmission of pathogens through blood transfusion is still of great concern to clinicians, patients and blood providers. Pathogen reduction technologies (PRT) have been successfully applied for the treatment of labile blood components, such as plasma, platelets and whole blood (WB), which are now used in routine in many countries. We report the clinical evaluation of suspension of red blood cells (RBC‐S) derived from the WB treated with riboflavin and UV light (RF+UV). Study Design and Methods: Seventy paediatric patients (0·3–17·1 years old) suffering from different malignant disorders were recruited and assigned to two groups: the control group (C) received transfusions of γ‐irradiated RBC‐S. The experimental group (T) received RBC‐S derived from WB, treated with RF+UV. Clinical efficacy was evaluated during follow‐up periods by Hb and Ht increments, and needs for transfusion support. Safety was assessed through active surveillance, recording post‐transfusion reactions, anti‐erythrocyte's antibody formation, haptoglobin and serum potassium levels. Results: The clinical efficacy of RBC‐S in both groups was similar: mean post‐transfusion Hb concentration (101·6 ± 7·57 g/l vs. 100 ± 8·3 g/l; P = 0·43), and Ht level (28·5 ± 2·42% vs. 28·2 ± 2·7%; P = 0·66). Transfusion of pathogen‐reduced RBC‐S did not increase the frequency of transfusion reactions and did not induce an excessive immune response in the follow‐up period. Conclusion: Transfusion of RBC‐S, obtained from pathogen‐reduced WB, is a promising method to increase the safety of blood component therapy for paediatric patients with malignant disorders without affecting clinical efficacy. A randomized clinical trial including more patients should follow this pilot study to confirm its results. [ABSTRACT FROM AUTHOR]

Moreover, the use of pathogen-reduced technologies makes it possible to increase the shelf life of pathogen-reduced platelets up to 7 days, as well as to release pathogen-inactivated plasma immediately without having to quarantine it. We plan to conduct a clinical study of pathogen-reduced blood products transfusion versus standard transfusion practice in children with oncological and malignant haematological diseases to determine the clinical and cost-effectiveness of this approach. Previously, we published the results of our clinical study, which included the determination of quality indicators [1] and clinical utilization of pathogen-reduced red blood cell suspension for transfusions in paediatric patients with various oncological and haematological diseases [2]. [Extracted from the article]