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SIGNIFICANCE: Fluorescent organic dyes provide imaging capabilities at cellular and sub-cellular levels. However, a common problem associated with some of the existing dyes such as the US FDA-approved indocyanine green (ICG) is their weak fluorescence emission. Alternative dyes with greater emission characteristics would be useful in various imaging applications. Complementing optical imaging, magnetic resonance (MR) imaging enables deep tissue imaging. Nano-sized delivery systems containing dyes with greater fluorescence emission as well as MR contrast agents present a promising dual-mode platform with high optical sensitivity and deep tissue imaging for image-guided surgical applications. AIM: We have engineered a nano-sized platform, derived from erythrocyte ghosts (EGs), with dual near-infrared fluorescence and MR characteristics by co-encapsulation of a brominated carbocyanine dye and gadobenate dimeglumine (Gd-BOPTA). APPROACH: We have investigated the use of three brominated carbocyanine dyes (referred to as BrCy106, BrCy111, and BrCy112) with various degrees of bromination, structural symmetry, and acidic modifications for encapsulation by nano-sized EGs (nEGs) and compared their resulting optical characteristics with nEGs containing ICG. RESULTS: We find that asymmetric dyes (BrCy106 and BrCy112) with one dibromobenzene ring offer greater fluorescence emission characteristics. For example, the relative fluorescence quantum yield ( ϕ ) for nEGs fabricated using 100    μ M of BrCy112 is ∼ 41 -fold higher than nEGs fabricated using the same concentrations of ICG. The dual-mode nEGs containing BrCy112 and Gd-BOPTA show a nearly twofold increase in their ϕ as compared with their single optical mode counterpart. Cytotoxicity is not observed upon incubation of SKOV3 cells with nEGs containing BrCy112. CONCLUSIONS: Erythrocyte nano-ghosts with dual optical and MR characteristics may ultimately prove useful in various biomedical imaging applications such as image-guided tumor surgery where MR imaging can be used for tumor staging and mapping, and fluorescence imaging can help visualize small tumor nodules for resection.

It is important to understand the dynamics of red blood cells (RBCs) in blood flow. This requires the formulation of coarse-grained RBC models that reproduce the hydrodynamic properties of blood accurately. One of the models that successfully reproduces the rheology and morphology of blood has been proposed by Fedosov et al. [Comput. Methods Appl. Mech. Eng. 199, 1937–1948 (2010)]. The proposed RBC model contains several parameters whose values are determined by either various experiments or physical requirements. In this study, we developed a new method of determining parameter values precisely from the fluctuations of the RBC membrane. Specifically, we studied the relationship between the spectra of the fluctuations and model parameters. Characteristic peaks were observed in the spectra, whose peak frequencies were dependent on the parameter values. In addition, we investigated the spectra of the radius of gyration. We identified the peaks originating from the spring potential and the volume-conserving potential appearing in the spectra. These results lead to the precise experimental determination of the parameters used in the RBC model. [ABSTRACT FROM AUTHOR]

COVID-19 infection is associated with a variety of vascular occlusive morbidities. However, a comprehensive understanding of how this virus can induce vascular complications remains lacking. Here, we show that a peptide fragment of SARS-CoV-2 spike protein, S192 (sequence 192-211), is capable of forming amyloid-like aggregates that can induce agglutination of red blood cells, which was not observed with low- and non-aggregated S192 peptide. We subsequently screened eight amyloid-binding molecules and identified BAM1-EG6, a benzothiazole amphiphile, as a promising candidate capable of binding to aggregated S192 and partially inhibiting its agglutination activity. These results provide new insight into a potential molecular mechanism for the capability of spike protein metabolites to contribute to COVID-19-related blood complications and suggest a new therapeutic approach for combating microvascular morbidities in COVID-19 patients.

This study aims to investigate the effects of hypoxically stored Red Blood Cells (RBCs) in a rat model of traumatic brain injury followed by severe hemorrhagic shock (HS) and resuscitation. RBCs were made hypoxic using an O2 depletion system (Hemanext Inc. Lexington, MA) and stored for 3 weeks. Experimental animals underwent craniotomy and blunt brain injury followed by severe HS. Rats were resuscitated with either fresh RBCs (FRBCs), 3-week-old hypoxically stored RBCs (HRBCs), or 3-week-old conventionally stored RBCs (CRBCs). Resuscitation was provided via RBCs transfusion equivalent to 70 % of the shed blood and animals were followed for 2 h. The control group was comprised of healthy animals that were not instrumented or injured. Post-resuscitation hemodynamics and lactate levels were improved with FRBCs and HRBCs, and markers of organ injury in the liver (Aspartate aminotransferase [AST]), lung (chemokine ligand 1 [CXCL-1] and Leukocytes count), and heart (cardiac troponin, Interleukin- 6 [IL-6] and Tumor Necrosis Factor Alpha[TNF-α]) were lower with FRBCs and HRBCs resuscitation compared to CRBCs. Following reperfusion, biomarkers for oxidative stress, lipid peroxidation, and RNA/DNA injury were assessed. Superoxide dismutase [SOD] levels in the HRBCs group were similar to the FRBCs group and levels in both groups were significantly higher than CRBCs. Catalase levels were not different than control values in the FRBCs and HRBCs groups but significantly lower with CRBCs. Thiobarbituric acid reactive substances [Tbars] levels were higher for both CRBCs and HRBCs. Hypoxically stored RBCs show few differences from fresh RBCs in resuscitation from TBI + HS and decreased organ injury and oxidative stress compared to conventionally stored RBCs.

Red blood cell (RBC) metabolic reprogramming upon exposure to high altitude contributes to physiological human adaptations to hypoxia, a multifaceted process critical to health and disease. To delve into the molecular underpinnings of this phenomenon, first, we performed a multi-omics analysis of RBCs from six lowlanders after exposure to high-altitude hypoxia, with longitudinal sampling at baseline, upon ascent to 5,100 m and descent to sea level. Results highlighted an association between erythrocyte levels of 2,3-bisphosphoglycerate (BPG), an allosteric regulator of hemoglobin that favors oxygen off-loading in the face of hypoxia, and expression levels of the Rhesus blood group RHCE protein. We then expanded on these findings by measuring BPG in RBCs from 13,091 blood donors from the Recipient Epidemiology and Donor Evaluation Study. These data informed a genome-wide association study using BPG levels as a quantitative trait, which identified genetic polymorphisms in the region coding for the Rhesus blood group RHCE as critical determinants of BPG levels in erythrocytes from healthy human volunteers. Mechanistically, we suggest that the Rh group complex, which participates in the exchange of ammonium with the extracellular compartment, may contribute to intracellular alkalinization, thus favoring BPG mutase activity.

BACKGROUND: Mechanical thrombectomy (MT) has become the gold standard care for treating acute ischemic stroke (AIS) due to large vessel occlusion. Emerging evidence suggests that understanding the composition of clots prior to intervention could be useful for the selection of neuroendovascular techniques, potentially improving the efficacy of treatments. However, current imaging modalities lack the ability to distinguish clot composition accurately and reliably. Since water content can influence signal intensity on CT and MRI scans, its assessment may provide indirect clues about clot composition. This study aimed to elucidate the correlation between water content and clot composition using human clots retrieved from stroke patients and experimentally generated ovine clots. MATERIALS AND METHODS: This study involved an analysis of ten clots retrieved from patients with AIS undergoing MT. Additionally, we created ten red blood cells (RBC)-rich and ten fibrin-rich ovine blood clots, which were placed in a human intracranial vascular model under realistic flow conditions. The water content and compositions of these clots were evaluated, and linear regression analyses were performed to determine the relationship between clot composition and water content. RESULTS: The regression analysis in human stroke clots revealed a significant negative association between RBC concentration and water content. We also observed a positive correlation between water content and both fibrin and platelets in ovine blood clots. Conclusion.

Spleen marginal zone (MZ) B cells are important for antibody responses against blood-borne antigens. The signals they use to detect exposure to blood are not well defined. Here, using intravital two-photon microscopy in mice, we observe transient contacts between MZ B cells and red blood cells that are in flow. We show that MZ B cells use adhesion G-protein-coupled receptor ADGRE5 (CD97) for retention in the spleen. CD97 function in MZ B cells depends on its ability to undergo autoproteolytic cleavage and signaling via Gα13 and ARHGEF1. Red blood cell expression of the CD97 ligand CD55 is required for MZ B cell homeostasis. Applying a pulling force on CD97-transfected cells using an optical C-trap and CD55+ beads leads to accumulation of active RhoA and membrane retraction. Finally, we show that CD97 deficiency leads to a reduced T cell-independent IgM response. Thus, our studies provide evidence that MZ B cells use mechanosensing to position in a manner that enhances antibody responses against blood-borne antigens.

Plasma medicine is a field that utilizes reactive species generated from atmospheric low-temperature plasmas for applications such as sterilization, blood coagulation, and cancer therapy. Commercial plasma devices are available for wound healing, but research on the chemical modifications induced by these plasmas is scarce. This study explores the chemical modifications in hemoglobin when exposed to a helium plasma dielectric barrier discharge, with the aim of explaining the potential mechanisms through which it contributes to blood coagulation and enhances wound healing. Optical microscopy of cold atmospheric plasma (CAP) treated whole capillary blood showed an increase in red blood cell (RBC) size and the formation of rouleaux structures. The treatment of whole blood leads to hemolysis of RBCs and the release of intracellular protein content. We then treated purified hemoglobin protein at physiological concentrations, which led to the formation of aggregates that could be observed using ion mobility mass spectrometry (IM–MS), size exclusion chromatography, and optical microscopy. The aggregates formed fibril-like structures as observed using atomic force microscopy. The formation of hemoglobin aggregates is hypothesized to be the result of new intermolecular interactions formed following the CAP-mediated protein oxidation. We studied the changes to hemoglobin structure after treatment with a CAP using high-resolution MS and found that the hemoglobin subunits are oxidized with the addition of at least 4 oxygen atoms each. The intact tetrameric hemoglobin structure remains unchanged; however, the monomeric and dimeric proteins adopt a more compact structure, as observed by IM–MS. We propose that CAP treatment of fresh blood leads to hemolysis, and that the extracellular protein, primarily hemoglobin, is oxidized leading to the formation of aggregates. [ABSTRACT FROM AUTHOR]

Summary: Background: Alterations in haematological, biochemical parameters and cytokine levels, were reported in patients with COVID-19, however, there is an underrepresentation of the African population, which could provide evidence for understanding SARS-CoV-2 pathogenesis and useful tools for clinical management of cases. In this study, we aimed to determine the haematological, biochemical and cytokine profile in Mozambican individuals with SARS-CoV-2. Methods: A cohort of 85 Mozambican individuals with RT-PCR SARS-CoV-2 results, was stratified into negative, asymptomatic, mild, moderate, and severe categories. Haematological, biochemical and cytokines measurement were performed on samples from the study participants. Principal component analysis (PCA) was performed to identify similar patterns among the study cases. Comparisons between groups were performed using the Kruskal-Wallis test. Receiver operating characteristic (ROC) and area under the curve (AUC) analysis were conducted to evaluate the ability of these parameters to distinguish severe from non-severe cases of SARS-CoV-2 infection. Results: SARS-CoV-2 infection was associated with a significant (p < 0.05) decrease in peripheral blood absolute counts of total lymphocytes and eosinophils, below the reference values along with no abnormal change (p > 0.05) in red blood cell count, haemoglobin, platelets and other red series parameters. At the serum level, SARS-CoV-2 infection was associated with an increase in serum levels of C-reactive protein (C-RP) and glucose above the reference values and to a significant reduction a significant (p < 0.05) reduction in levels of interferon-gamma (INF-γ), Tumour Necrosis Factor alfa (TNF-α) and the interleukin 1 beta (IL-1β) and IL-6 in severe cases, when compared to negative cases. Haematological, biochemical and cytokine profiles segregate severe from non-severe cases of COVID-19 with an excellent performance of C-RP (AUC = 0.95; p < 0.001) and good performance of lymphocytes (AUC = 0.88; p < 0.001) and IL-15 (AUC = 0.86; p < 0.001). Conclusion: The lack of variation in red and platelet series, coupled with a decrease in the levels of classical pro-inflammatory in severe cases, deviates from what has been reported in other contexts suggesting, that there may be peculiarities in COVID-19 manifestation within the context of this study population. Furthermore, these results identify parameters with potential for clinical management of COVID-19 and therefore good resource allocation, particularly for severe cases. [ABSTRACT FROM AUTHOR]

Summary Red blood cell (RBC) antigen matching beyond ABO and RhD is commonly recommended for patients with sickle cell disease (SCD) and thalassaemia. We present an updated systematic literature review to inform evidence‐based guidelines on RBC matching. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool was used to develop recommendations. Six new observational studies (4 prospective, 2 retrospective) were identified. The six studies reported on 583 patients in total, including cross‐over designs, with sample sizes from 10 to 343. Studies were heterogeneous, utilising varying degrees of RBC matching and different definitions for ‘extended’ matching. All reported on alloimmunisation. One study reported on molecular matching. The reported prevalence of alloimmunisation using limited matching was 0%–50% and with extended matching was 0%–24%. Eighty‐two patients were alloimmunised before study entry. The risk of bias across studies was moderate to critical. The guideline panel recommends that ABO, RhDCcEe, and K‐compatible RBCs are selected for individuals with SCD and thalassaemia, even in the absence of alloantibodies, and that RBCs which are antigen‐negative to already existing clinically significant antibodies are chosen. There is a need for comparative research to define the benefit, impact, cost‐effectiveness, and feasibility of extended RBC matching strategies to prevent alloimmunisation. [ABSTRACT FROM AUTHOR]

Babesia bovis, an apicomplexan intraerythrocytic protozoan parasite, causes serious economic loss to cattle industries around the world. Infection with this parasite leads to accumulation of infected red blood cells (iRBCs) in the brain microvasculature that results in severe clinical complications known as cerebral babesiosis. Throughout its growth within iRBCs, the parasite exports various proteins to the iRBCs that lead to the formation of protrusions known as "ridges" on the surface of iRBCs, which serve as sites for cytoadhesion to endothelial cells. Spherical body proteins (SBPs; proteins secreted from spherical bodies, which are organelles specific to Piroplasmida) are exported into iRBCs, and four proteins (SBP1-4) have been reported to date. In this study, we elucidated the function of SBP3 using an inducible gene knockdown (KD) system. Localization of SBP3 was assessed by immunofluorescence assay, and only partial colocalization was detected between SBP3 and SBP4 inside the iRBCs. In contrast, colocalization was observed with VESA-1, which is a major parasite ligand responsible for the cytoadhesion. Immunoelectron microscopy confirmed localization of SBP3 at the ridges. SBP3 KD was performed using the glmS system, and effective KD was confirmed by Western blotting, immunofluorescence assay, and RNA-seq analysis. The SBP3 KD parasites showed severe growth defect suggesting its importance for parasite survival in the iRBCs. VESA-1 on the surface of iRBCs was scarcely detected in SBP3 KD parasites, whereas SBP4 was still detected in the iRBCs. Moreover, abolition of ridges on the iRBCs and reduction of iRBCs cytoadhesion to the bovine brain endothelial cells were observed in SBP3 KD parasites. Immunoprecipitation followed by mass spectrometry analysis detected the host Band 3 multiprotein complex, suggesting an association of SBP3 with iRBC cytoskeleton proteins. Taken together, this study revealed the vital role of SBP3 in ridge formation and its significance in the pathogenesis of cerebral babesiosis. Author summary: Babesia bovis causes a high-mortality complication called cerebral babesiosis in cattle, similar to cerebral malaria in humans. Both complications are caused by the cytoadhesion of infected red blood cells (iRBCs) to the host brain endothelial cells. These parasites export numerous proteins to the host iRBCs and produce protrusions on the iRBCs that are called ridges for B. bovis and knobs for Plasmodium falciparum. Ridges and knobs play an important role in cytoadhesion as they are the sites of adherence; however, the molecules responsible for ridge formation remain unknown. In this study, we showed that SBP3 is a crucial protein for ridge formation. The SBP3 knockdown parasites showed severe growth defects and abolition of ridges on the iRBCs, and cytoadhesion of iRBCs to the bovine brain endothelial cells was significantly reduced. An immunoprecipitation experiment suggested an association of SBP3 with the host Band 3 multiprotein complex. Although there is no similarity in amino acid sequences, we suggest SBP3 to be a functional analog of KAHRP in P. falciparum. In summary, our results shed light on the molecular mechanism of ridge formation and the pathogenesis of B. bovis. [ABSTRACT FROM AUTHOR]

ABSTRACT Photosensitizers and pigments in raw meat such as porphyrins, riboflavin, and myoglobin after incorporation with light beam prompt the generation of singlet oxygen (1O2) from triplet oxygen (3O2) and cause oxidative rancidity of meat products. In this study, the results of photooxidation reactions of sheep erythrocyte (red blood cell) model as a model rich in hemoglobin and phospholipids bilayer, and oleic acid model were obtained by 1H NMR spectroscopy, TBARS assay, and iodometric titration. In both models, the rate of lipid photooxidation in the presence of hydroalcoholic extracts of Turmeric (Curcuma longa L.) and Cumin (Cuminum cyminum L.) as natural antioxidants, Butyl hydroxytoluene (BHT) as a synthetic antioxidant, and sodium azide (NaN3) as a well‐known 1O2 scavenger were decreased in the order of NaN3 > Turmeric > Cumin > BHT. It was proven that during the photooxidation process, there is a direct association between the amount of flavonoid compounds and 1O2 scavenging. [ABSTRACT FROM AUTHOR]

Opsonization of red blood cells that retain mitochondria (Mito+ RBCs), a feature of systemic lupus erythematosus (SLE), triggers type I interferon (IFN) production in macrophages. We report that monocytes (Mos) co-produce IFN and mature interleukin-1β (mIL-1β) upon Mito+ RBC opsonization. IFN expression depended on cyclic GMP-AMP synthase (cGAS) and RIG-I-like receptors' (RLRs) sensing of Mito+ RBC-derived mitochondrial DNA (mtDNA) and mtRNA, respectively. Interleukin-1β (IL-1β) production was initiated by the RLR antiviral signaling adaptor (MAVS) pathway recognition of Mito+ RBC-derived mtRNA. This led to the cytosolic release of Mo mtDNA, which activated the inflammasome. Importantly, mIL-1β secretion was independent of gasdermin D (GSDMD) and pyroptosis but relied on IFN-inducible myxovirus-resistant protein 1 (MxA), which facilitated the incorporation of mIL-1β into a trans -Golgi network (TGN)-mediated secretory pathway. RBC internalization identified a subset of blood Mo expressing IFN-stimulated genes (ISGs) that released mIL-1β and expanded in SLE patients with active disease. [Display omitted] • Mos co-produce type I IFN and IL-1β upon Mito+ RBC opsonization • IFN and IL-1β expression rely on sensing RBC-derived mtDNA and mtRNA • IL-1β secretion is MxA mediated and independent of GSDMD and pyroptosis • GPA+ blood Mos expressing IFN and IL-1β are expanded in active SLE SLE is an interferonopathy, but blocking IFN does not benefit all patients. Caielli et al. found that SLE monocytes co-produce IFN and IL-1β, a phenotype recapitulated upon in vitro Mito+ RBC opsonization. Cytosolic sensing of mitochondrial nucleic acids induces MxA, which enables IL-1β secretion independently of GSDMD and pyroptosis. [ABSTRACT FROM AUTHOR]

Although the pathological significance of myeloid cell heterogeneity is still poorly understood, new evidence indicates that distinct macrophage subsets are characterized by specific metabolic programs that influence disease onset and progression. Within this scenario, distinct subsets of macrophages, endowed with high rates of heme catabolism by the stress-responsive enzyme heme oxygenase-1 (HO-1), play critical roles in physiologic and pathological conditions. Of relevance, the substrates of HO-1 activity are the heme groups that derive from cellular catabolism and are converted into carbon monoxide (CO), biliverdin and Fe2+, which together elicit anti-apoptotic, anti-inflammatory activities and control oxidative damage. While high levels of expression of HO-1 enzyme by specialized macrophage populations (erythrophagocytes) guarantee the physiological disposal of senescent red blood cells (i.e. erythrocateresis), the action of HO-1 takes on pathological significance in various diseases, and abnormal CO metabolism has been observed in cancer, hematological diseases, hypertension, heart failure, inflammation, sepsis, neurodegeneration. Modulation of heme catabolism and CO production is therefore a feasible therapeutic opportunity in various diseases. In this review we discuss the role of HO-1 in different pathological contexts (i.e. cancer, infections, cardiovascular, immune-mediated and neurodegenerative diseases) and highlight new therapeutic perspectives on the modulation of the enzymatic activity of HO-1. [ABSTRACT FROM AUTHOR]

In order to improve the delivery performance of curcumin (CUR) in liver cancer cells, we prepared a targeted and reduction‐sensitive prodrug, folic acid‐polyethylene glycol‐disulfide bond‐curcumin (FA‐PEG‐SS‐CUR). The synthesis involved the conjugation of CUR with NH2‐PEG‐NH2 through a disulfide bond, followed by the connection of CUR‐SS‐PEG‐NH2 to FA‐COOH via acylation. The resultant FA‐PEG‐SS‐CUR prodrug self‐assembled into nano micelles in aqueous solutions, displaying excellent dispersibility with an approximate particle size of 119 nm. In vitro drug release studies demonstrated the sensitivity of FA‐PEG‐SS‐CUR to glutathione (GSH), displaying sustained release performance. After 72 h, FA‐PEG‐SS‐CUR exhibited a drug release rate of 38% at low GSH concentration and 59% at high GSH concentration. Notably, FA‐PEG‐SS‐CUR micelles exhibited favorable biocompatibility. The hemolysis rate resulting from co‐incubation with red blood cells remained below 3%. Furthermore, cytotoxicity experiments unveiled the substantial cytotoxicity of FA‐PEG‐SS‐CUR micelles against HepG2 tumor cells. Cellular uptake studies confirmed the greater internalization of FA‐PEG‐SS‐CUR by HepG2 cells compared to the non‐targeted PEG‐SS‐CUR. The findings highlight the potential of FA‐PEG‐SS‐CUR as an ideal drug delivery system for CUR due to its facile synthesis and strong self‐assembly performance. [ABSTRACT FROM AUTHOR]

Bisphenol F (BPF) is an emerging contaminant extensively used in the pharmaceutical, chemical, and food industries, exerting deleterious effects on human and wildlife health. Therefore, the current study was conducted to assess the toxicity induced by BPF in rohu Labeo rohita using multiple biomarkers such as oxidative stress, activity of antioxidant enzymes, biochemical parameters, histology, and genotoxicity. Fish were separated into four groups (T1–T4). Group T1 served as a control (0 μg/L), while Groups T2, T3, and T4 were exposed to BPF concentrations of 600 μg/L, 1200 μg/L, and 1800 μg/L, respectively, for 21 days. Results showed a significant (p < 0.05) increase in oxidative biomarkers (thiobarbituric acid reactive substance [TBARS] and reactive oxygen species [ROS]), while the concentration of antioxidant biomarkers (peroxidase [POD], superoxide dismutase [SOD], reduced glutathione [GSH], and catalase) was significantly (p < 0.05) decreased with the rising concentration of BPF in the liver, gills, and kidney of fish. Significant reduction (p < 0.05) in biochemical parameters was measured from collected whole blood, including red blood cells (RBCs), hemoglobin (HGB), mean corpuscular HGB (MCH), MC volume (MCV), hematocrit (HCT), MC HGB concentration (MCHC), platelets, low‐density lipoprotein (LDL), cholesterol, high‐density lipoprotein (HDL), total proteins, very LDL (VLDL), albumin and globulin, while white blood cells (WBCs), neutrophils, triglycerides, aspartate aminotransferase (AST), blood glucose, and alanine transaminase (ALT) levels were increased significantly (p < 0.05). Comet assay showed the DNA damage potential of BPF in erythrocytes. Histological examination showed that exposure to BPF causes several degenerative effects in the soft tissues (gills, liver, and kidney) of treated fish. It is concluded that BPF induces deleterious effects via disruptions in histological, genotoxic, and biochemical alterations in several organs of exposed fish. [ABSTRACT FROM AUTHOR]

Hereditary spherocytosis (HS) is the most prevalent form of congenital hemolytic anemia, being caused by genetic mutations in genes encoding red blood cell cytoskeletal proteins. Mutations in the ANK1 and SPTB genes are the most common causes of HS.; however, pathogenicity analyses of these mutations remain limited. This study identified three novel heterozygous mutations in 3 HS patients: c.1994 C > A in ANK1, c.5692 C > T, and c.3823delG in SPTB by whole-exome sequencing (WES) and validated by Sanger sequencing. To investigate the functional consequences of these mutations, we studied their pathogenicity using in vitro culture erythroblast derived from CD34 + stem cells. All three mutations lead to the generation of a premature stop codon. Real-time PCR assay revealed that the two SPTB mutations resulted in reduced SPTB mRNA expression, suggesting a potential role for the nonsense-mediated mRNA degradation pathway. For the ANK1 mutation, gene expression was not reduced but was predicted to produce a truncated version of the ANK1 protein. Flow cytometry analysis of red blood cell-derived microparticles (MPs) revealed that HS patients had higher MP levels compared to normal subjects. This study contributes to the current understanding of the molecular mechanisms underlying mutations in the ANK1 and SPTB genes in HS. [ABSTRACT FROM AUTHOR]

The effect of serum glucose-to-potassium ratio (GPR) on cerebrovascular diseases has been previously validated. However, the value of the GPR in patients with severe intracerebral hemorrhage (ICH) requiring ICU admission remains unclear. This study aimed to investigate the association between the GPR and the clinical prognosis of critically ill patients with ICH. This study identified patients with severe ICH requiring ICU admission from the Medical Information Mart for Intensive Care (MIMIC-IV) database and divided them into quartiles based on GPR levels. Outcomes included 30-day, 90-day, and 1-year mortality rates. The association between the GPR and clinical outcomes in critically ill patients with ICH was elucidated using Cox proportional hazards regression analysis and restricted cubic splines. In total, 2018 patients (53.8% male), with a median age of 70 years, were enrolled in the study. The 30-day, 90-day, and 1-year mortality rates were 23.9%, 30.1%, and 38.4%, respectively. Per multivariate Cox proportional hazards analysis, an elevated GPR was significantly associated with all-cause mortality. After adjusting for age, sex, Charlson Comorbidity Index, white blood cell count, red blood cell count, platelet count, and Glasgow Coma Scale, patients with an elevated GPR had a higher 30-day mortality (hazard ratio [HR]: 1.32; 95% confidence interval [CI]: 1.22–1.42; P < 0.001), 90-day mortality (HR: 1.27; 95% CI: 1.18–1.37; P < 0.001) and 1-year mortality (HR: 1.22; 95% CI: 1.14–1.31; P < 0.001) when analyzed as a continuous variable. Furthermore, analysis using restricted cubic splines demonstrated a consistent and progressive escalation in the risk of all-cause mortality with an elevated GPR. The GPR was significantly associated with short- and long-term all-cause mortality in critically ill patients with ICH. This finding demonstrates that GPR may be useful in identifying patients with ICH at a high risk of all-cause mortality. [ABSTRACT FROM AUTHOR]

The article discusses cases of spurious lymphocyte differential counts caused by the presence of target cells in automated hematology analyzers. The study highlights discrepancies between different analyzers and manual counts, with target cells identified in all cases. The presence of unlysed target cells interfered with the differential analysis, leading to inaccurate results. The study emphasizes the importance of understanding analyzer technology to identify and address spurious results effectively. [Extracted from the article]

Background Methods Results Conclusions The resuscitation of trauma patients with critical bleeding may follow a formulaic approach using high ratios of blood components or a viscoelastic haemostatic assay (VHA) guided approach. The aim of this study was to compare the two strategies for resuscitation of shocked trauma patients.This was a registry‐based cohort study including shocked trauma patients from two trauma centres–one practising a formulaic approach, with VHA unavailable during trauma resuscitation and the other practicing a VHA‐guided resuscitation strategy. The primary outcome was the total units of blood components transfused in 24 h after adjusting for differences in baseline characteristics and time to death.Between 01 Jan 2020 and 31 Dec 2022, 152 eligible patients were categorised to the formulaic group and 40 to the VHA group. Prehospital times were longer in the formulaic group (2.0 vs. 1.4 h), and more patients in the VHA group (38% vs. 17%) were transfused prehospital blood components. Formulaic resuscitation was associated with significantly more blood components transfused (adjusted incidence rate ratio 1.5; 95%CI: 1.4–1.7, p < 0.001). Using a formulaic approach, patients were administered more red blood cells, plasma and platelets, but fewer cryoprecipitate. There was no significant association of the formulaic approach with in‐hospital mortality (adjusted odds ratio 2.4; 95%CI: 0.7–8.0, p = 0.17).Given the cost and potential adverse effects of blood component transfusions, VHA‐guided transfusion strategies present an attractive option, particularly among centres managing high volumes of shocked patients. Further trials, enrolling the population most likely to benefit from precision transfusion strategies, are indicated. [ABSTRACT FROM AUTHOR]

Revealing the spatial distribution and regional differences of red blood cell distribution width (RDW) reference values in the healthy Chinese population is important for the monitoring, diagnosis and prevention of the top chronic diseases in the disease spectrum in China. Medical indicator data were matched with geographical data and environmental pollution data to predict RDW reference values for the whole region of China using ridge regression analysis, support vector machine and BP neural network. Taylor diagrams and assignment methods were used to select the optimal model, and the spatial distribution was mapped according to the prediction results of the optimal model, and the intervals of RDW reference values for different age groups of healthy people in China were redefined. It was suggested that the reference values of RDW in the young and middle-aged groups in China were divided into low-value areas in the north (12.31,12.80) and high-value areas in the south (12.80,13.18); the reference values of RDW in the elderly group were divided into low-value areas in the north (11.28,12.60) and high-value areas in the south (12.60,13.91).In turn, it can provide a more accurate reference basis in the monitoring, diagnosis and prevention of chronic diseases at the top of the disease spectrum. [ABSTRACT FROM AUTHOR]

Schiff bases possess a range of unique physical, chemical and medicinal properties, which contribute to their potency as biological agents. A Schiff base was synthesized, which consisted of 4-chloro aniline and vanillin. The successful formation of the compound was confirmed by their comparable FTIR, UV–Vis, 1HNMR and 13CNMR spectra. The compound was analyzed using X-ray crystallography, which revealed that it crystallizes in the monoclinic system with the space group P21/c. The Hirshfeld surface analysis revealed valuable information about the intermolecular interactions present in the crystal lattice. The most common contacts observed were between hydrogen and hydrogen, as well as carbon and hydrogen. The obtained fluorescence values of 375 nm and 412 nm at excitation wavelength 322 nm strongly indicated the luminescent nature of the compound. The thermal stability of the compound was assessed through thermogravimetric analysis (TGA). DFT was used to optimize the geometry using the B3LYP/cc-pVDZ basis set. The compound exhibited an energy gap of 2.35 electron volts (eV). According to the analysis of molecular electrostatic potential, C and O atoms were found to be electrophilic. According to Mulliken charge analysis, C atoms possess both positive and negative charges, hydrogen atoms exclusively carry positive charges, and Cl, O and N atoms exclusively carry negative charges. Upon analysis of the molecule, the electron localization function discovered that the atoms of carbon, nitrogen and chlorine exhibited delocalized electron density. Also, the localized orbital locator identified the localized orbital positions in the hydrogen atoms. The reduced density gradient (RDG) maps exhibit a wide range of noncovalent interactions. In comparison to the standard amoxicillin, the synthesized compound demonstrated moderate antimicrobial efficacy against the gram-positive bacteria Klebsiella pneumoniae and the fungi Candida albicans. The compound’s concentration-dependent antioxidant and anti-inflammatory properties were demonstrated through in vitro biological evaluation using 2,2-diphenyl-1-picrylhydrazyl and human red blood cell (HRBC) methods. The compound was docked using the proteins 7BYE and 4LEB were chosen from both organisms. The lowest binding attractions obtained were -3.40 kcal/mol for 7BYE and -4.51 kcal/mol for 4LEB. To investigate the stability of the protein–ligand complex, molecular dynamic simulation was employed. The ligands in silico toxicity potentialities were analyzed using seven toxicity models and the results indicated that the ligand is biocompatible. [ABSTRACT FROM AUTHOR]

The article discusses the relevance of the E756del common variant in the PIEZO1 gene for haemolytic anaemia and hepatic iron overload, particularly in patients with dehydrated hereditary stomatocytosis (DHS). The variant is prevalent in the African-descent population and has been associated with increased red blood cell dehydration, mild anaemia, alterations in iron balance, and protection against malaria. The study analyzed a cohort of patients with hereditary erythrocyte and iron metabolism defects, highlighting the impact of the E756del variant on clinical parameters and iron metabolism. The findings suggest that the E756del variant functions as a polymorphism with mild to moderate effects on haemolytic anaemia and hepatic iron overload, emphasizing the importance of monitoring iron balance in affected individuals. [Extracted from the article]

Decompensated cirrhotic patients experience severely increased intestinal permeability and bacterial translocation. Thus, autologous blood salvaged during deceased donor liver transplantation (DDLT) may be contaminated with enteric bacteria. We aimed to evaluate bacterial contamination of autologous blood salvaged during DDLT and its association with post-transplant bacteremia. In 30 patients undergoing DDLT, bacterial culture was performed in salvaged autologous blood samples: one before graft reperfusion (non-leukoreduced) and two after graft reperfusion (non-leukoreduced and leukoreduced). The primary outcome was bacterial contamination of salvaged autologous blood. Seven of 30 patients (23.3%) were positive for bacteria (3 enteric/4 non-enteric) before graft reperfusion while 11 patients (36.7%) were positive (5 enteric/6 non-enteric) after graft reperfusion. Six of 7 patients who were positive for bacteria before graft reperfusion were positive after graft reperfusion with the same bacteria. Only 4 of 11 contaminated blood samples were converted to negative after leukoreduction. Post-transplant bacteremia risk was insignificantly greater in patients who received autologous blood with bacteria than in patients without bacteria (30.0% vs. 5.0%, P = 0.06). We found contamination of salvaged autologous blood with enteric bacteria throughout DDLT and incomplete performance of leukoreduction, indicating high bacterial load. The potential association between contaminated autotransfusion and post-transplant bacteremia warrants further validation in a larger prospective study. Clinical trial notation: This study was registered at the Clinical Research Information Service (CRiS; https://cris.nih.go.kr; No. KCT0007223; principal registration investigator: Sangbin Han, date of registration: April 25, 2022). [ABSTRACT FROM AUTHOR]

Antibiotic resistance has been threatening public health for a long period, while the COVID pandemic aggravated the scenario. To combat antibiotic resistance strains, host defense peptides (HDPs) mimicking molecules have attracted considerable attention. Herein, we reported a series of polycarbonates bearing cationic lysine amino acid residues that could mimic the mechanism of action of HDPs and possess broad‐spectrum antimicrobial activity. Moreover, those polymers had negligible toxicity toward red blood cells and mammalian cells. The membrane‐disruption mechanism endows the lysine‐containing polycarbonates with low possibility of resistance development and the fast killing kinetics, making them promising candidates for antimicrobial development. [ABSTRACT FROM AUTHOR]

Plasmodium falciparum malaria parasites invade and multiply inside red blood cells (RBCs), the most iron-rich compartment in humans. Like all cells, P. falciparum requires nutritional iron to support essential metabolic pathways, but the critical mechanisms of iron acquisition and trafficking during RBC infection have remained obscure. Parasites internalize and liberate massive amounts of heme during large-scale digestion of RBC hemoglobin within an acidic food vacuole (FV) but lack a heme oxygenase to release porphyrin-bound iron. Although most FV heme is sequestered into inert hemozoin crystals, prior studies indicate that trace heme escapes biomineralization and is susceptible to nonenzymatic degradation within the oxidizing FV environment to release labile iron. Parasites retain a homolog of divalent metal transporter 1 (DMT1), a known mammalian iron transporter, but its role in P. falciparum iron acquisition has not been tested. Our phylogenetic studies indicate that P. falciparum DMT1 (PfDMT1) retains conserved molecular features critical for metal transport. We localized this protein to the FV membrane and defined its orientation in an export-competent topology. Conditional knockdown of PfDMT1 expression is lethal to parasites, which display broad cellular defects in iron-dependent functions, including impaired apicoplast biogenesis and mitochondrial polarization. Parasites are selectively rescued from partial PfDMT1 knockdown by supplementation with exogenous iron, but not other metals. These results support a cellular paradigm whereby PfDMT1 is the molecular gatekeeper to essential iron acquisition by blood-stage malaria parasites and suggest that therapeutic targeting of PfDMT1 may be a potent antimalarial strategy. [ABSTRACT FROM AUTHOR]

Background: The prevalence of steatotic liver disease (SLD) in patients with type 2 diabetes (T2DM) exceeds 50%. This study aimed to investigate the clinical characteristics of SLD and liver fibrosis in Chinese patients with T2DM. Methods: Inpatients from 2021 to 2023 were included in the study. Fatty liver index (FLI) and fibrosis-4 (FIB-4) were calculated to assess hepatic steatosis and fibrosis respectively. Statistical analysis was completed by SPSS v25 and GraphPad Prism v8.0.1. Results: Of the 1466 participants, about one-third of the patients in T2DM-SLD group were diagnosed with liver fibrosis (LF), and the percentage of patients over 50 years old was 85.9%. Patients with SLD had higher levels of BMI, blood pressure, liver enzymes, fasting blood glucose (FBG), HbA1c, C-peptide, total cholesterol (TC) and triglyceride (TG) (P<0.05 for all). Patients with liver fibrosis had lower TC, TG, hemoglobin (Hb), erythrocyte count (RBC), leukocyte count (WBC) and platelet (PLT) levels (P<0.05 for all). Compared with simple T2DM and SLD-NLF (non-liver fibrosis) groups, for patients over 50 years old, the prevalence of coronary heart disease, stroke, tumor, and diabetic nephropathy was higher in patients with liver fibrosis. Liver fibrosis might be the risk factor of arterial stiffness, stroke, coronary heart disease and numbness based on multivariable logistic regression analysis. Conclusion: Hepatic steatosis and fibrosis were common in patients with T2DM. Liver fibrosis was relevant to many macrovascular and microvascular diabetic complications. [ABSTRACT FROM AUTHOR]

Subarachnoid hemorrhage (SAH) is the deadliest form of hemorrhagic stroke; however, effective therapies are still lacking. Perfluorocarbons (PFCs) are lipid emulsion particles with great flexibility and their much smaller size as compared to red blood cells (RBCs) allows them to flow more efficiently within the blood circulation. Due to their ability to carry oxygen, a specific PFC-based emulsion, PFC-Oxygent, has been used as a blood substitute; however, its role in cerebral blood flow regulation is unknown. Adult C57BL/6 wildtype male mice were subjected to an endovascular perforation model of SAH followed by an intravenous (i.v.) injection of 9 ml/kg PFC-Oxygent or no treatment at 5 h after SAH. At 48 h after SAH, functional and anatomical outcomes were assessed. We found that SAH resulted in significant neurologic and motor deficits which were prevented by PFC-Oxygent treatment. We found that SAH-induced vasospasm, reduced RBC deformability, and augmented endothelial dysfunction were also restricted by PFC-Oxygent treatment. Moreover, mitochondrial activity and fusion proteins were also markedly decreased as assessed by oxidative phosphorylation (OXPHOS) after SAH. Interestingly, PFC-Oxygent treatment brought the mitochondrial activity close to the basal level. Moreover, SAH attenuated the level of phosphorylated AMP-activated protein kinase (pAMPK), whereas PFC treatment improved pAMPK levels. These data show the beneficial effects of PFC-Oxygent in limiting the severity of SAH. Further studies are needed to fully understand the mechanism through which PFC-Oxygent exerts its beneficial effects in limiting SAH severity. [ABSTRACT FROM AUTHOR]

Background Study Design and Methods Results Discussion Many children with sickle cell disease (SCD) who suffer a stroke receive chronic transfusion therapy (CTT) indefinitely; however, their adulthood neurologic outcomes have not been reported. Understanding these outcomes is critical to inform decisions regarding curative therapy in childhood.In this retrospective study, we described a cohort of adults with SCD and a history of childhood stroke who received care at a single center and compared their outcomes with matched subjects without childhood stroke using chi2 and Mann–Whitney U tests.Of 42 subjects with childhood stroke, all received CTT for secondary stroke prophylaxis. Five (11%) developed recurrent stroke. The rate of stroke was similar in subjects with and without childhood stroke (0.7 vs. 1.1 per 100 person·years, p = .63). Both cohorts exhibited evidence of iron overload (median ferritin 2227 vs. 1409 ng/dL, p = .10) and alloimmunization (45% vs. 45%, p = 1.0), despite receiving care in a comprehensive SCD program.For adults with SCD who had a childhood stroke, our results suggest CTT returns the risk of stroke to that of age‐matched stroke naïve patients with SCD. [ABSTRACT FROM AUTHOR]

Snakebites inflict significant injuries on humans and animals, posing a severe global public health challenge due to high mortality and morbidity rates. This study presents results against the venoms of Bothrops jararaca and Bothrops neuwiedi using sixteen synthetic hybrid molecules containing thiophene and triazoles, designated as 6a–h and 7a–h. The compounds were assessed for their ability to inhibit proteolytic and plasma coagulant activities induced by the snake venoms, and their toxicity was analyzed. Most derivatives demonstrated nontoxicity through in silico analysis with the Osiris Property Explorer tool and in vitro cytotoxic hemocompatibility on red blood cells. Notably, only derivative 6e exhibited toxicity to erythrocytes, while 6b, 6d, 7c, and 7f displayed mutagenic, tumorigenic, or adverse effects on the reproductive system. Derivatives 6a, 6c–h, 7c–e, 7g, or 7h effectively inhibited the coagulating activity of B. jararaca venom, while 6a–b, 6d–e, 6h, or 7a–f inhibited coagulation induced by B. neuwiedi venom. All derivatives demonstrated inhibition of the proteolytic activity caused by B. jararaca venom, and derivatives 6a–d and 7e–f inhibited the activity of B. neuwiedi venom. Consequently, these derivatives exhibited varying degrees of efficacy in countering two crucial toxic effects of B. jararaca or B. neuwiedi venoms, suggesting their potential as antivenoms against both species. [ABSTRACT FROM AUTHOR]

The article "Granuloma Faciale-Like Lesion of the Palate: A Previously Unreported Entity" published in Oral Diseases in 2024 describes a rare case of a granuloma faciale-like lesion in the oral cavity of a 75-year-old woman. The lesion resembled granuloma faciale histologically and showed signs of vasculitis and fibrinoid necrosis. The patient experienced spontaneous healing after biopsy, and treatment with topical dapsone and tacrolimus prevented recurrence. This case represents a unique instance of a mucosal granuloma faciale-like lesion, distinct from eosinophilic angiocentric fibrosis. [Extracted from the article]

AbstractSickle cell disease (SCD) is a prevalent inherited blood disorder arising from a single point mutation that results in substitution of valine with glutamic acid in the Beta hemoglobin chain, making red blood cells assume a banana shape under low oxygen state. It is most prevalent in sub-Saharan Africa, affecting approximately 2% of the population in Mali. This study aimed to evaluate the iron status and associated hematological parameters in SCD patients at steady state in an environment with a high prevalence of iron deficiency. A cross-sectional study was conducted at the Center de Recherche et de Lutte contre la Drépanocytose (CRLD) in Bamako, Mali, involving 757 SCD patients aged 10 to 29 years. Iron deficiency was defined as serum ferritin < 20 ng/mL, while iron overload was associated with serum ferritin > 500 ng/mL. The study population consisted of 171 (22.6%) hemolytic phenotypes (SS and Sβ0) and 586 (77.4%) viscous phenotypes (SC and Sβ+). Iron deficiency was found in 19 SCD patients (2.5%), with a higher prevalence in the SC phenotype (68.4%). All iron-deficient subjects exhibited microcytosis (MCV < 80 fL) and hypochromia (MCH < 26 pg). Hemoglobin levels < 12 g/dL were observed only in homozygous SCD patients. Low reticulocyte counts were noted in iron-deficient subjects with SC and Sβ+ phenotypes, but not in iron-deficient SS subjects. Serum C-reactive protein (CRP) was normal (< 10 mg/L) in all iron-deficient subjects, excluding iron deficiency due to chronic inflammation. Iron deficiency was observed among 2.5% of the study population, with a predominant occurrence among those with SC phenotype. All iron deficient subjects had microcytosis and hypochromia. Hemoglobin levels below 12 g/dL were only found in homozygous SCD patients. Additionally, low reticulocyte counts were noted in iron deficient patients with SC and Sβ+ phenotypes, though not in those with the SS phenotype. These findings contribute to the understanding of iron status in SCD patients in an African context and highlights the importance of monitoring iron levels in these population to prevent complications associated with iron deficiency or overload. [ABSTRACT FROM AUTHOR]

ABSTRACT Caesalpinia digyna (Family: Fabaceae) is traditionally used in Ayurvedic medicine for various medicinal purposes, including as a treatment for wounds, leprosy, skin diseases, fever, diabetes, etc. Although the root and stem of this plant have a significant medicinal value, there was little research on the leaves of this plant. This study aimed to investigate the qualitative phytochemical profile and evaluate the in vitro cytotoxic, anti‐inflammatory, antioxidant, and antiarthritic activities, as well as the in vivo anti‐inflammatory and analgesic activities, of C. digyna leaf extract. The methanolic extract of C. digyna leaves was prepared using an ultrasonic‐assisted extraction process. In vitro and in vivo anti‐inflammatory activities were evaluated using the hypotonicity‐induced hemolysis and carrageenan‐induced paw edema methods, respectively. Additionally, the extract was assessed for in vitro DPPH (1, 1‐diphenyl‐2‐picrylhydrazyl) free radical scavenging, antiarthritic (protein denaturation), and in vivo analgesic (acetic acid‐induced writhing and tail immersion) activities. Brine shrimp lethality bioassay (BSLB) showed moderate cytotoxic activity (LC50 = 2.25 μg/mL) compared with the standard vincristine sulfate (LC50 = 1.61 μg/mL). In vitro, anti‐inflammatory activity exhibited 85.13% (IC50 value = 2.51 μg/mL) inhibition of Human Red Blood Cell (HRBC) membrane lysis at a concentration of 2000 μg/mL whereas in vivo anti‐inflammatory study exerted its maximum effect (p < 0.05) at 400 mg/kg bw dose. This extract also showed significant antioxidant (IC50 = 0.218 μg/mL), antiarthritic (83.61% inhibition) activity, and moderate analgesic effect (p < 0.05) in both methods. These research findings indicated that C. digyna leaves extract has potent antioxidant, analgesic, and anti‐inflammatory effects which can be used as a supplementary medication for inflammatory pain‐relieving factors. In future, finding the mechanism involved in these effects could have significant impact on clinical science. [ABSTRACT FROM AUTHOR]

ABSTRACT Pure red cell aplasia (PRCA) is a rare but significant complication following major ABO‐incompatible allogeneic hematopoietic stem cell transplantation (HSCT). The persistence of recipient B lymphocytes producing anti‐donor isohemagglutinins leads to reticulocytopenia and anemia, often resulting in transfusion dependence. Current treatment options for post‐HSCT PRCA are limited and frequently yield suboptimal responses, complicating patient management. Herein, we report three cases of post‐HSCT PRCA successfully managed with daratumumab, a monoclonal antibody targeting CD38‐expressing plasma cells. All patients demonstrated rapid reticulocyte recovery and transfusion independence after daratumumab treatment, despite prior treatment failures. These findings suggest that daratumumab may provide a more effective therapeutic approach, with a favorable safety profile compared to traditional therapies. Given its demonstrated efficacy and safety, daratumumab warrants consideration as a first‐line treatment for post‐HSCT PRCA, potentially improving patient quality of life and reducing transfusion‐related complications. Further studies should explore optimal dosing and long‐term outcomes. [ABSTRACT FROM AUTHOR]

Background: About half of the world's populations are infected with Helicobacter pylori, which may create atherogenic lipid profiles and contribute to atherosclerosis and related cardiovascular disease. Furthermore, it has been connected to hematological symptoms like anemia. Even though the high prevalence of H.pylori and its associated complications, including cardiovascular disease and anemia, in Ethiopia, there is little data regarding the risk factors associated with H.pylori infection, such as hematologic parameters, electrolyte imbalances, and lipid profiles. Methods: A comparative cross-sectional study design with a consecutive sampling technique was employed at Jimma Medical Center among 108 dyspeptic patients. Five (5) ml of blood samples were collected from each participant, and serum was extracted and analyzed using a COBAS 6000 core for the lipid and electrolyte, and whole blood was used with a SYSMEX XN 550 to determine hematological parameters. Data were entered in to Epi-data version 4.6 and exported to SPSS version 25 for analysis. Simple descriptive statistics and chi-square test were used to present the socio-demographic characteristics of the study subjects. Student t-test was used for data comparison and p-value < 0.05 was considered statistically significant. Results: H.pylori infected patients had significantly decreased levels of red blood cell count (p = 0.002), hemoglobin (p = 0.012), mean corpuscular hemoglobin concentration (p < 0.001), platelet count (p = 0.001), and sodium level (p = 0.006) when compared to the uninfected group. However, total cholesterol (p = 0.001), and low density lipoprotein (p = 0.021) were increased in H.pylori infected patients when compared to the uninfected group. Conclusions: This study revealed that H.pylori infection can cause derangements of hematologic parameters, electrolyte imbalances, and alterations of lipid parameters which considered as risk factors for anemia and cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Purpose: Elite swimmers often schedule altitude training camps ahead of major events in an attempt to maximize performance. However, the relationships between altitude-induced hematological changes, markers of training adaptation, and performance changes in such context are unclear. This study assessed hematological status, markers of daily adaptation, and swimming performance in elite middle-distance and distance swimmers during a 22-day altitude training camp at 2,320 m, 2 weeks prior to World Championship qualification competition. Methods: Venous blood was obtained and total hemoglobin mass (tHbmass) measured (CO rebreathing) in 7 elite swimmers (4 females, 3 males) 8 days before and on day 22 of the altitude camp. Resting heart rate, peripheral oxygen saturation, urinary specific gravity, body mass, fatigue and self-reported sleep duration and quality were monitored daily during the altitude camp. Swimming performance was assessed through a standardized set (6 sets of 4 maximal repetitions of 100 m front crawl) on days 3, 10 and 17 of the camp, and at sea level competitions (200 m–1,500 m) immediately after the camp, and 2 weeks later. Results: tHbmass (+5.6 ± 3.3%; range: 2.1%–11.0%; p < 0.05), red blood cell count, hemoglobin concentration, hematocrit increased at the end of the training camp (p < 0.05). Performance at altitude improved throughout the camp (+1.4 ± 0.4%; range: 0.7%–2.5%; p < 0.05). No significant relationship was noted between hematological changes, the change in altitude performance and any of the monitored daily markers of adaptation during the camp. Compared to the swimmers' previous personal best, competition performances did not improve immediately (2.5% ± 1.9% slower times) and 2 weeks after altitude (1.2% ± 1.4% slower times). Conclusion: The 22-day altitude training camp at 2,320 m was beneficial for elite swimmers' tHbmass, hematological status and performance at altitude, but these benefits did not clearly translate into enhanced sea level performance immediately after or 2 weeks later. The present study confirms the large inter-individual variability in hematological responses to altitude training, and that the improvement in performance at altitude and sea level may depend on factors other than the increase in tHbmass alone. [ABSTRACT FROM AUTHOR]

Silicon dioxide nanoparticles are receiving increasing attention due to their new properties and wide applications. The aim of this study was to investigate the cytotoxic potential of 300 nm SiO2 nanospheres on erythrocytes using thermal diffusivity values. Cytotoxicity was correlated with thermal diffusivity of the hemolysates; thermal values ​​were from 10.00 ± 0.40 × 10− 4 cm2/s to 12.20 ± 0.07 × 10− 4 cm2/s. The concentrations tested were 50, 100, 200, 400 and 800 µg/ml of silica nanoparticles. To evaluate cytotoxicity, human erythrocytes were obtained. Hemolytic damage in red blood cells had an exponential behavior dependent on the concentration of SiO2 nanostructures. The use of concentrations of 800 µg/ml exceeds the limit of compatibility for human red blood cells. Antioxidant enzyme quantification assays were also performed in which a dose-dependent depletion of catalase activity levels and an increase in glutathione S-transferase was observed. Therefore, oxidative stress was suggested as a mechanism of toxicity in erythrocytes. [ABSTRACT FROM AUTHOR]

Objectives This study aimed to establish a comprehensive human erythrocyte antigen (HEA) frequency data set for Koreans. It also sought to develop a mobile app that facilitates the calculation of the frequencies of specific antigen-negative red blood cell units and the average number of units required for antigen typing. Methods Human erythrocyte antigen frequencies were compiled from large-scale blood donor data and 5 previous papers. Based on the collected data, we developed a mobile calculator app for HEA frequency and evaluated its usability. Results Human erythrocyte antigen frequency data for 20 blood group systems, including the ABO, Rh, MNS, Duffy, Kidd, and Diego systems, were established. The app was designed to enable users to select the desired phenotype from a drop-down menu and display the calculated frequency at the bottom. The number of units required for antigen typing to find 1 compatible red blood cell unit was also displayed. Five users participated in app evaluation and rated the functionality and information categories highly. In quizzes prompting users to calculate frequencies using the app, all participants provided correct answers, confirming the app's user-friendly functionality. Conclusions This app, which encompasses comprehensive HEA frequency data, is expected to find multiple uses in transfusion medicine, including optimizing blood bank workflow and defining rare blood groups in Korea. [ABSTRACT FROM AUTHOR]

Objective The aim of this work was to resolve the uncertainty of whether transfusion of fresher red blood cells (RBCs) is better or not with regard to the safety and efficacy. Methods This systematic review was performed in accordance with our protocol registered on PROSPERO (https://www.crd.york.ac.uk/prospero/display%5frecord.php?ID=CRD42022379183). Results After a literature search, 13,247 records were identified, and 26 randomized controlled trials (RCTs) involving 53,859 participants were eligible and included in this review. The results in our review suggested that there was no significant effect of fresher vs older RBCs on mortality (relative risk [RR] = 1.04; 95% CI, 0.99-1.09; P =.39; I 2 = 0%), transfusion reactions (RR = 0.87; 95% CI, 0.57-1.33; P =.64; I 2 = 0%). However, the transfusion of fresher RBCs might increase the risk of nosocomial infection (RR = 1.11; 95% CI, 1.02-1.20; P =.02; I 2 = 0%), whereas there was no significant difference in the fresh vs old subgroup (RR = 0.87; 95% CI, 0.68 to 1.12; P =.28; I 2 = 0%). Conclusion Our study updated and reinforced the evidence of previously published systematic reviews that support the safety and efficiency of current practice of issuing the oldest available RBCs in the blood bank inventory. [ABSTRACT FROM AUTHOR]

Objective We report a rare case of acute hemolytic reactions caused by immunoglobulin (Ig)M anti-M antibody and present a literature review. Case Report A 61-year-old male patient who underwent blood transfusion developed fever, chills, soy sauce–colored urine, and changes in laboratory test results, including persistently decreased hemoglobin levels, neutrophilia, elevated lactate dehydrogenase level, acute kidney injury, mild acute liver injury, and activation of the coagulation system, indicating acute hemolytic transfusion reaction (AHTR). Antibody screening and major crossmatching results indicated weak positive at 37°C for both posttransfusion and pretransfusion sample. Subsequent serological examinations indicated the presence of IgM anti-M antibodies in plasma but the direct antiglobulin and elution tests were negative. Antibody hemolytic activity assay confirmed AHTR caused by anti-M. The transfused red blood cells were MM and the patient is NN. These signs and symptoms disappeared rapidly and required no additional interventions before discharge. Conclusion The accurate diagnosis of anti-M antibody–mediated acute hemolysis is essential for guiding treatment decisions. [ABSTRACT FROM AUTHOR]

Introduction: Children are more vulnerable to anaemia due to their rapid growth, which requires an expanding erythroid mass and a high tissue iron demand. Anaemia can negatively impact psychomotor and cognitive development and can lead to a decline in immunity. Reticulocytes are precursors to erythrocytes and make up about 1% (ranging from 0.5% to 2.5%) of circulating erythrocytes. The reticulocyte content serves as a measurement of haemoglobin within the reticulocyte and correlates directly with the functional availability of iron in the bone marrow. Consequently, it is considered one of the strongest predictors of Iron Deficiency (ID). The Reticulocyte Haemoglobin Content (RET-Hb) level is useful for diagnosing anaemia before it clinically manifests in a patient. Aim: To assess the effectiveness of RET-Hb content as a predictor for early response to oral iron therapy in comparison to haemoglobin levels. Materials and Methods: This prospective interventional study was conducted in the Department of Paediatrics at a tertiary care Hospital in Thrissur, Central Kerala, India, over a period of 18 months, from December 2019 to June 2021. A total of 44 samples were included in the study, and socio-demographic details were collected using a semistructured proforma from patients with haemoglobin levels below the mean reference value. Baseline haemogram parameters {Mean Corpuscular Volume (MCV), Mean Corpuscular Haemoglobin (MCH), Mean Corpuscular Haemoglobin Concentration (MCHC), Red Cell Distribution Width (RDW), Haemtocrit (HCT)}, reticulocyte indices, and ferritin levels were measured before administering oral iron therapy (T0). These parameters were reassessed after seven days (T1) and 30 days (T2) following the initiation of therapy. The Chi-square test was used to assess the association between various factors, and Pearson's correlation coefficient was utilised to find the correlation. Results: The mean age of the participants was 3.46±2.2 years, with 24 males and 20 females included in the study. The mean RET-Hb was 21.15±1.71 pg before the initiation of treatment, which significantly increased to 23.37±1.95 pg and 25.77±1.56 pg at days 7 and 30, respectively. The haemoglobin level increased from 8.37±1.25 g/L to 8.55±1.19 g/L and 9.72±0.98 g/L at T1 and T2, respectively, which was statistically significant. The Absolute Reticulocyte Count (RET#) also showed a significant early increase after initiating treatment. Conclusion: These findings indicate that RET-Hb and RET# are reliable early predictors of response to iron therapy, alongside haemoglobin levels, and can be used as effective alternatives. [ABSTRACT FROM AUTHOR]

Background/Objectives: Chemical and carcinogenic risk in workplace are linked to an increase of the incidence of cancer in exposed workers. The aim of this observational study was to identify an association between exposure to chemical risk and changes in hematochemical parameters of workers exposed. Methods: The study examined blood count parameters performed on 4523 employees of Sapienza University of Rome from September 2019 to February 2020. A total of 1402 workers in research laboratories, exposed to chemical risk and carcinogens, was compared with a cohort of 3121 blood donors, in apparently good health, matched for age, sex, and period of blood collection. Results: Multivariate analysis demonstrated acrylamide is the most frequently associated chemical with significant changes between the groups. It is related to an increase in monocytes and MPV, a reduction of lymphocytes, platelets, and red series values, while MCH remained unchanged. Formaldehyde reveals the same changes as acrylamide, with the exception of the percentage of lymphocytes, red blood cells, and HB, which remain unchanged. Other chemicals and carcinogens show variations for few blood count parameters. Conclusions: The present study found out a significant change in blood count values in workers exposed to acrylamide and formaldehyde. It also showed an increase in the mean monocyte value in employees exposed to carcinogenic risk, compared to non-exposed, with the exception of Trypan Blue. The implementation of efficient health surveillance remains of critical importance. These data should be compared with those from follow-up studies. [ABSTRACT FROM AUTHOR]

Blood is a common biological fluid in forensic investigations, offering significant evidential value. Currently employed presumptive blood tests often lack specificity and are sample destructive, which can compromise downstream analysis. Within this study, the development of an optical biosensor for detecting human red blood cells (RBCs) has been explored to address such limitations. Aptamer-based biosensors, termed aptasensors, offer a promising alternative due to their high specificity and affinity for target analytes. Aptamers are short, single-stranded DNA or RNA sequences that form stable three-dimensional structures, allowing them to bind to specific targets selectively. A nanoflare design has been employed within this work, consisting of a quenching gold nanoparticle (AuNP), DNA aptamer sequences, and complementary fluorophore-labelled flares operating through a fluorescence resonance energy transfer (FRET) mechanism. In the presence of RBCs, the aptamer–flare complex is disrupted, restoring fluorescence and indicating the presence of blood. Two aptamers, N1 and BB1, with a demonstrated binding affinity to RBCs, were selected for inclusion within the nanoflare. This study aimed to optimise three features of the design: aptamer conjugation to AuNPs, aptamer hybridisation to complementary flares, and flare displacement in the presence of RBCs. Fluorescence restoration was achieved with both the N1 and BB1 nanoflares, demonstrating the potential for a functional biosensor to be utilised within the forensic workflow. It is hoped that introducing such an aptasensor could enhance the forensic workflow. This aptasensor could replace current tests with a specific and sensitive reagent that can be used for real-time detection, improving the standard of forensic blood analysis. [ABSTRACT FROM AUTHOR]

Competitive athletes are often exposed to extreme physiological loading, resulting in over excessive mechanotransduction during their acute intensive training sessions and competitions. Individual differences in their genetics often affect how they cope with these challenges, as reflected in their high performances. Olympic Medalists are prohibited from providing atypical values in the Hematological Module of the Athlete Biological Passport. Since there was no aphysiological result and the Athlete maintained his innocence, a whole genome sequence analysis was carried out on him and his parents, with the primary focus on the PIEZO ion channels encoding gene. PIEZO1 is known to participate in homeostatic regulation even on a whole-body level, including the regulation of physical performance, circulatory longevity of red blood cells and cell fate determination of mesenchymal stem cells in relation to hydrostatic pressure. However, PIEZO2 was found to be the principal mechanosensory ion channel for proprioception. These regulatory mechanisms play a pivotal role in mechanotransduction and intensive exercise moments. Interestingly, two variances of uncertain significance of PIEZO1 were found that may explain the atypical values of the Athlete. Furthermore, two additional variances in SDC2, the syndcan-2 encoding gene, were identified in trans position that may influence the crosstalk between PIEZO2 and PIEZO1, with more likely relevance to the detected atypical values. After all, based on the found variances of PIEZO1 and syndecan-2, it cannot be ruled out that these VUS variants may have caused or impacted the exhibited outlier findings of the ABP Hematological Module of the Athlete. [ABSTRACT FROM AUTHOR]

Congenital anemias include a broad range of disorders marked by inherent abnormalities in red blood cells. These abnormalities include enzymatic, membrane, and congenital defects in erythropoiesis, as well as hemoglobinopathies such as sickle cell disease and thalassemia. These conditions range in presentation from asymptomatic cases to those requiring frequent blood transfusions, exhibiting phenotypic heterogeneity and different degrees of severity. Despite understanding their different etiologies, all of them have a common pathophysiological origin with congenital defects of erythropoiesis. We can find different types, from congenital sideroblastic anemia (CSA), which is a bone marrow failure anemia, to hemoglobinopathies as sickle cell disease and thalassemia, with a higher prevalence and clinical impact. Recent efforts have focused on understanding erythropoiesis dysfunction in these anemias but, so far, deep gene sequencing analysis comparing all of them has not been performed. Our study used Quant 3′ mRNA-Sequencing to compare transcriptomic profiles of four sickle cell disease patients, ten thalassemia patients, and one rare case of SLC25A38 CSA. Our results showed clear differentiated gene map expressions in all of them with respect to healthy controls. Our study reveals that genes related to metabolic processes, membrane genes, and erythropoiesis are upregulated with respect to healthy controls in all pathologies studied except in the SLC25A38 CSA patient, who shows a unique gene expression pattern compared to the rest of the congenital anemias studied. Our analysis is the first that compares gene expression patterns across different congenital anemias to provide a broad spectrum of genes that could have clinical relevance in these pathologies. [ABSTRACT FROM AUTHOR]