Alterations In Erythrocytes Research Articles

Correction: Cyto-genotoxic Alterations in Erythrocytes of Fish, Channa Punctatus Exposed to Benzo[a]Pyrene

Correction: Cyto-genotoxic Alterations in Erythrocytes of Fish, Channa Punctatus Exposed to Benzo[a]Pyrene

Probing erythrocytes as sensitive and reliable sensors of metabolic disturbances in the crosstalk between childhood obesity and insulin resistance: findings from an observational study, in vivo challenge tests, and ex vivo incubation assays

BackgroundAlthough insulin resistance (IR) is among the most frequent and pathogenically relevant complications accompanying childhood obesity, its role in modulating and exacerbating obesity pathophysiology has not yet been completely clarified.MethodsTo get deeper insights into the interplay between childhood obesity and IR, we leveraged a comprehensive experimental design based on a combination of observational data, in vivo challenge tests (i.e., oral glucose tolerance test), and ex vivo assays (i.e., incubation of erythrocytes with insulin) using a population comprising children with obesity and IR, children with obesity without IR, and healthy controls, from whom plasma and erythrocyte samples were collected for subsequent metabolomics analysis.ResultsChildren with concomitant IR showed exacerbated metabolic disturbances in the crosstalk between endogenous, microbial, and environmental determinants, including failures in energy homeostasis, amino acid metabolism, oxidative stress, synthesis of steroid hormones and bile acids, membrane lipid composition, as well as differences in exposome-related metabolites associated with diet, exposure to endocrine disruptors, and gut microbiota. Furthermore, challenge tests and ex vivo assays revealed a deleterious impact of IR on individuals’ metabolic flexibility, as reflected in blunted capacity to regulate homeostasis in response to hyperinsulinemia, at both systemic and erythroid levels.ConclusionsThus, we have demonstrated for the first time that metabolite alterations in erythrocytes represent reliable and sensitive biomarkers to disentangle the metabolic complexity of IR and childhood obesity. This study emphasizes the crucial need of addressing inter-individual variability factors, such as the presence of comorbidities, to obtain a more accurate understanding of obesity-related molecular mechanisms.

Coenzyme Q10 supplementation affects cellular ionic balance: relevance to aging.

Aging results into disruptive physiological functioning and cellular processes that affect the composition and structure of the plasma membrane. The plasma membrane is the major regulator of ionic homeostasis thatregulates the functioning of membrane transporters and exchangers. Coenzyme Q10 is a lipid-soluble antioxidant molecule that declines during aging and age-associated diseases. The presentstudy aims to explore the role of Coenzyme Q10 supplementation to rats during aging on membrane transporters and redox biomarkers. The studywas conducted on young and old male Wistar rats supplemented with 20 mg/kg b.w. of Coenzyme Q10 per day. After a period of 28days, rats were sacrificed and erythrocyte membrane was isolated. The result exhibits significant decline in biomarkers of oxidative stress in old control rats when compared with young control. The effect of Coenzyme Q10 supplementation was more pronounced in old rats. Thefunctioning of membrane transporters and Na+/H+ exchanger showed potential return to normal levels in the Coenzyme Q10 treated rats. Overall, the results demonstrate that Coenzyme Q10 plays an important role in maintaining redox balance in cells which interconnects with membrane integrity. Thus, Coenzyme Q10 supplementation may play animportant role in protecting age related alterations inerythrocyte membrane physiology.

Differential Responses of Young and Old Erythrocytes Stored with Vitamin C and Vitamin E in Additive Solution-7.

Oxidative stress (OS) causes biochemical and morphological alterations in erythrocytes. The primary factors contributing to OS are aging and storage. Antioxidants significantly alleviate OS. Therefore, this study aimed to investigate the response of young and old erythrocytes to vitamin C and vitamin E during storage. Erythrocytes were separated into young and old by the Percoll method. Each erythrocyte subpopulation was categorized into the i) Control (additive solution-7 [AS-7]) and ii) vitamin C and vitamin E in AS-7 (VC+VE) groups and stored for 21 days at 4°C. OS, antioxidant, and aging markers were analyzed on days 1, 14, and 21. The activity of antioxidant enzymes was similar throughout storage in young cells. However, superoxide dismutase activity elevated in old cells (Control and VC+VE) on days 1 and 21. Catalase (CAT) activity increased on days 14 and 21, whereas glutathione peroxidase (GPX) increased on days 1 and 14 in old Controls. However, in old VC+VE, CAT increased on day 21 and GPX increased on day 1. Advanced oxidation protein products, superoxides, glutathione, and uric acid increased in old cells throughout storage. Malondialdehyde decreased in old VC+VE compared with old Control on days 14 and 21. Sialic acids and glutamate oxaloacetate transaminase activity were higher in young cells compared to old cells. Young cells exhibited lower oxidative changes throughout storage. Vitamin C and vitamin E were effective in maintaining the redox balance in old cells. These findings emphasize the need for specific approaches for different subpopulations during erythrocyte banking.

Exploring the Impact of Naphthalene (Polycyclic Aromatic Hydrocarbons) on Anabas testudineus (Bloch) through Dose-Specific Bioenzymological Analysis.

This study addresses the increasing concern about naphthalene, a polycyclic aromatic hydrocarbon (PAH), highlighting its growing threats to the environment and aquatic life. The research examines its impact on Anabas testudineus (Bloch) through a detailed dose-specific bioenzymological analysis. Experimental fish groups were exposed to T1 (0.71 mg/L) and T2 (1.42 mg/L) naphthalene concentrations, representing 25 and 50% of the LC50 value, respectively, over a 1-21 day period. Following the experiment, water samples underwent physicochemical analysis, while fish tissues were examined for diverse bioenzymological parameters. Among these parameters, aspirate aminotransferase (AST) and alanine aminotransferase (ALT) serve as crucial indicators for monitoring the physiological status of fish and addressing pollution induced by PAHs, especially naphthalene. Statistical significance was observed in morpho-pathological changes and erythrocyte alterations, particularly the presence of tear-drop appearance (Tr) positively interacting with swelled cells (Sc), vacuolated cells (Va), and sickle cells (Sk) (P < 0.05). These findings highlight tear-drop appearance (Tr) as a significant biomarker in response to naphthalene exposure. The observed changes in A. testudineus tissue bioenzymology, apoptosis, and erythrocytic alterations were exposure and dose-dependent. The research highlights the significance of overseeing and controlling PAH concentrations in aquatic ecosystems to ensure the well-being of A. testudineus (Bloch).

Plasmodium falciparum selectively degrades α-spectrin of infected erythrocytes after invasion.

Plasmodium falciparum is the causative agent of severe malaria that causes millions of deaths globally. The parasite invades human red blood cells and induces a cascade of alterations in erythrocytes for development and proliferation. Remodeling the host erythrocytic cytoskeleton is a necessary process during parasitization, but its regulatory mechanisms remain to be elucidated. In this study, we observed that erythrocytic α-spectrin is selectively degraded after P. falciparum invasion, while β-spectrin remained intact. We found that the α-spectrin chain was profoundly ubiquitinated by E3 ubiquitin ligase and degraded by the 26S proteasome. E3 ubiquitin ligase activity was regulated by P. falciparum phosphatidylinositol 3-kinase (PfPI3K) signaling. Additionally, blocking the PfPI3K-ubiquitin-proteasome pathway in P. falciparum-infected red blood cells reduced parasite proliferation and infectivity. This study deepens our understanding of the regulatory mechanisms of host and malarial parasite interactions and paves the way for the exploration of novel antimalarial drugs.

Red Blood Cell Adenylate Energetics Is Related to Endothelial and Microvascular Function in Long COVID.

Adenine nucleotides play a critical role in maintaining essential functions of red blood cells (RBCs), including energy metabolism, redox status, shape fluctuations and RBC-dependent endothelial and microvascular functions. Recently, it has been shown that infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) might lead to morphological and metabolic alterations in erythrocytes in both mild and severe cases of coronavirus disease (COVID-19). However, little is known about the effects of COVID-19 on the nucleotide energetics of RBCs nor about the potential contribution of nucleotide metabolism to the long COVID syndrome. This study aimed to analyze the levels of adenine nucleotides in RBCs isolated from patients 12 weeks after mild SARS-CoV-2 infection who suffered from long COVID symptoms and to relate them with the endothelial and microvascular function parameters as well as the rate of peripheral tissue oxygen supply. Although the absolute quantities of adenine nucleotides in RBCs were rather slightly changed in long COVID individuals, many parameters related to the endothelial and microcirculatory function showed significant correlations with RBC adenosine triphosphate (ATP) and total adenine nucleotide (TAN) concentration. A particularly strong relationship was observed between ATP in RBCs and the serum ratio of arginine to asymmetric dimethylarginine-an indicator of endothelial function. Consistently, a positive correlation was also observed between the ATP/ADP ratio and diminished reactive hyperemic response in long COVID patients, assessed by the flow-mediated skin fluorescence (FMSF) technique, which reflected decreased vascular nitric oxide bioavailability. In addition, we have shown that patients after COVID-19 have significantly impaired ischemic response parameters (IR max and IR index), examined by FMSF, which revealed diminished residual bioavailability of oxygen in epidermal keratinocytes after brachial artery occlusion. These ischemic response parameters revealed a strong positive correlation with the RBC ATP/ADP ratio, confirming a key role of RBC bioenergetics in peripheral tissue oxygen supply. Taken together, the outcomes of this study indicate that dysregulation of metabolic processes in erythrocytes with the co-occurring endothelial and microvascular dysfunction is associated with diminished intracellular oxygen delivery, which may partly explain long COVID-specific symptoms such as physical impairment and fatigue.

Impact of Chlorella vulgaris Bioremediation and Selenium on Genotoxicity, Nephrotoxicity and Oxidative/Antioxidant Imbalance Induced by Polystyrene Nanoplastics in African Catfish (Clarias gariepinus)

Contamination of the environment with nano- and microplastic particles exerts a threatening impact on the aquatic ecosystems and sustainable catfish aquaculture. The presence of nanoplastics has been found to have a detrimental impact on both aquatic and terrestrial ecosystems. The present study examines the effect of polystyrene nanoplastics (PS NPs) on the DNA, erythrocytes, oxidative status and renal histology of catfish, in addition to the potential protective effects of Chlorella vulgaris bioremediation and selenium to hinder this effect. Six equal groups of fish were used as follows: Group 1 served as a control group and received water free from PS NPs; Group 2 was exposed to PS NPs at a concentration of 5 mg/L; Group 3 was exposed to PS NPs (5 mg/L) + selenium (1 mg/kg diet); Group 4 was exposed to PS NPs (5 mg/L) + C. vulgaris (25 g/kg diet); Group 5 was supplemented with C. vulgaris (25 g/kg diet); and Group 6 was supplemented with selenium (1 mg/kg diet). The exposure period was 30 days. The results indicated that PS NPs induced oxidative stress by significantly elevating malondialdehyde activities and slightly reducing antioxidant biomarkers, resulting in DNA damage, increased frequency of micronuclei, erythrocyte alterations, and numerous histopathological alterations in kidney tissue. Selenium and C. vulgaris significantly ameliorated the oxidative/antioxidant status, reducing DNA damage, micronucleus frequency, erythrocyte alterations, and improving the morphology of kidney tissue. Nevertheless, further research is needed for a profound understanding of the mechanism behind the toxicity of nano-microplatics in aquatic systems.

Erythrocyte alterations in specimens of Danio rerio caused by exposure to metformin

The antidiabetic drug metformin is widely prescribed around the world. However, its permanence in different environmental concentrations has been associated with adverse toxicological effects in organisms that do not target its therapeutic action. In the aquatic environment, fish such as the Zebrafish (Danio rerio) have been considered potential bioindicators of environmental impacts and used as experimental models in toxicological studies due to the sensitivity of these species to different types of contaminants, including pharmaceuticals. Thus, this study aimed to analyze metformin's cytotoxic effects on Danio rerio erythrocytes. The animals were submitted to different concentrations of the drug (50 µg/L, 100 µg/L, 150 µg/L, and 10000 µg/L) for 365 days and subsequently observed employing light microscopy and scanning electron microscopy (SEM) to evaluate the alterations that occurred. Exposure of animals to metformin led to significant erythrocyte cell abnormalities across all tested concentrations, with a particularly pronounced effect at the higher concentration previously defined as the NOEC (No Observed Effect Concentration). Remarkable abnormalities included cytoplasmic vacuoles, echinocytes, and vesicle-like cytoplasmic fragments. These findings suggest that metformin, even at concentrations similar to those found in nature and at the NOEC level, exhibits cytotoxic potential in D. rerio, raising concerns about its potential health impacts.

Visualization of poikilocytosis as an emerging erythrocytic biomarker for fish health assessment

AbstractFish health assessment is essential for maintaining sustainable aquatic ecosystems and ensuring the well‐being of wild and farmed fish populations. Hematological parameters are crucial indicators of fish health, with poikilocytosis emerging as a fundamental marker with significant diagnostic value. Poikilocytosis refers to abnormally shaped erythrocytes in bloodstream, reflecting underlying physiological and pathological conditions. Poikilocytosis can occur in various fish species and can be influenced by environmental stressors, infectious agents, nutritional deficiencies, and exposure to pollutants. Morphological alterations in erythrocytes, such as acanthocytes, echinocytes, dacrocytes, schistocytes, spherocytes, and codocytes are common poikilocytes in fish. Understanding the relationship between poikilocytosis and fish health has important implications for disease diagnosis, monitoring, surveillance, and management. By quantifying poikilocytic changes, researchers and veterinarians can differentiate normal variations from pathological conditions, facilitating targeted interventions and treatment strategies. While most studies have focused on heavy metal toxicity, stressors, nutritional deficiencies, pollutants, and therapeutics, the etiological induction of poikilocytosis in fish health has been overlooked. Nonetheless, poikilocytosis remains a valuable biomarker for assessing fish health and their environment. This review highlights piscine poikilocytosis as a significant fish hematological biomarker and its importance in understanding their health and culture conditions.

Unmasking the morphological alteration of erythrocytes among women suffering from PCOS

Dyslipidemia is frequently observed in polycystic ovarian syndrome (PCOS). Changes in plasma lipid levels potentially alter erythrocyte membrane lipid composition due to lack of inbuilt lipid synthesis machinery. Therefore, development of morphologically altered erythrocytes in PCOS patients with dyslipidemia is expected. However, this has not been established so far. So, we took this opportunity to explore the morphological alterations among dyslipidemic PCO women. We recruited thirty-five dyslipidemic PCOS women (satisfying Rotterdam criteria, without medication) and twenty-five age-matched healthy controls. Scanning electron microscopy revealed a significant increase in the number of stomatocytes, acanthocytes, and echinocytes in the PCO group. PCO group showed a considerable decrease in plasma antioxidant levels. Elevated lipid peroxidation, protein carbonylation, and decreased free thiol group in erythrocyte membrane in PCOS suggest oxidative degradation of the erythrocyte membrane. Elevated intracellular ROS levels, increased methemoglobin formation, and a decrease in NADPH methemoglobin reductase in PCOS also indicate altered physicochemical property of hemoglobin due to oxidative overload. Additionally, these patients exhibit a rise in erythrocyte membrane cholesterol and triglyceride, which promotes the membrane to become less fluidic and less fragile. Thus, these results corroborate a potential role in altering erythrocyte morphology among dyslipidemic PCO women.

Alcohol-induced hormonal and metabolic alterations in plasma and erythrocytes—a gender-based study

Purpose This study aimed to understand the gender-specific alcohol-induced biochemical changes and TBARS association with the endocrine system. Methods Human male and female subjects ranging from 35 ± 10 years old with an 8-10-year drinking history were included in the study. Results The results demonstrated that testosterone levels were lower in male alcoholics and higher in female alcoholics, as well as higher estrogen and cortisol levels in both genders. In addition, we found lower T3, T4, and thyroid-stimulating hormone (TSH) levels in alcoholics of both sexes. Furthermore, plasma TBARS, protein carbonyls, nitrite, and nitrate levels increased significantly with concomitant decrease in reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities in both male and female alcoholics. Furthermore, erythrocyte lysate nitrite and nitrate levels membrane total cholesterol, phospholipid and cholesterol/phospholipid (C/P) ratio with lower total membrane proteins in both genders of alcoholics. SDS-PAGE analysis of erythrocyte membrane proteins revealed increased density of band 3, protein 4.1, 4.2, 4.9 and glycophorins, whereas decreases in spectrin (α and β) were observed in both genders of alcoholics. Besides, alcoholics of both sexes had a lower ability to resist osmotic hemolysis. Plasma TBARS was negatively correlated with testosterone, TSH, T3 and T4 in male alcoholics, moreover, estradiol and cortisol were positively correlated in males and females respectively. Conclusion Female alcoholics may be more susceptible to osmotic hemolysis due to increased erythrocyte membrane lipid peroxidation with decreased antioxidant status, which results in an altered membrane C/P ratio and membrane protein composition.

Cytotoxicity and immunological impact of Trypanosoma sp. infection on blood parameters of wild African catfish, Clarias gariepinus

Fish trypanosomiasis is a common blood parasitic disease transmitted by aquatic invertebrates, such as leeches. This study aims to shed light on the cytotoxicity of Trypanosoma sp. on erythrocytes and its impacts on the innate immune response (serum lysozyme activity, nitric oxide production, phagocytic activity, serum total protein, and globulin) in wild African catfish, Clarias gariepinus. One hundred catfish were examined using blood smears stained with Giemsa and confirmed with PCR. The prevalence of infection was found to be 10% by microscope detection and 15% by PCR. The morphological identification of Trypanosoma as Trypanosoma mukasai was determined. Additionally, this study included previously undescribed features of Trypanosoma, such as the width of the anterior and posterior body, the length of the posterior pale region, and the number of folds. Various alterations in erythrocytes were observed, totaling 54.57%. Nuclear abnormalities, including fragmented nuclei, eccentric nuclei, and micronuclei, were also reported. Infected fish showed a reduction in serum total protein and globulin levels, while nitric oxide production, lysozyme activity, and phagocytic activity exhibited a significant increase compared to non-infected fish. We believe that our findings will contribute valuable data to the morphological and molecular identification of Trypanosoma sp. in African catfish, as well as their cytotoxic impact.

Acute and Subchronic Exposure of the Common Carp (Cyprinus carpio) to Herbicide S-Metolachlor

S-metolachlor is one of the most frequently used herbicides worldwide. However, toxicity studies of this herbicide to aquatic organisms are scarce. In the present study, two experiments were conducted to test the effects of S-metolachlor on common carp, one of the most economically important fish species, with a distribution throughout the world: (1) 96 h acute semi-static toxicity test, aiming to determine LC50; (2) a subchronic semi-static test that lasted 28 days, in which juvenile carp were exposed to 3%, 8%, and 25% of previously determined LC50—0.5 mg·L−1, 1.4 mg·L−1, and 4.1 mg·L−1, respectively. Several biomarkers were employed to assess fish responses to toxicants. Blood biochemistry analysis and nuclear alterations of erythrocytes did not show any difference among experimental groups. Semi-quantitative histopathological analysis revealed mild alterations in the gills and liver, where oedema of secondary epithelium of gills and leukocyte infiltration in liver were significantly higher in fish exposed to 1.4 mg·L−1 and 4.1 mg·L−1. Histopathological indices in liver, as well as the total histopathological index, also showed significantly higher scores in the same groups. Bioconcentration factors of S-metolachlor ranged from 3.2 to 9.4, depending on the experimental group.

Investigating the impact of APOE4 genotype on the association between cerebral blood flow and haematological properties in mid‐life adults

AbstractBackgroundCarriership of the apolipoprotein ε4 (APOE4) allele confers a heightened risk for the development of Alzheimer’s disease (AD). Cerebral blood flow (CBF) is decreased in prodromal and established AD, however findings in the preclinical stage are mixed, with some studies reporting increases. CBF can be impacted by many factors including the haematocrit. We investigated in a cohort at risk of developing AD how haematological variables relate to CBF and if this relationship is differentially moderated by APOE4.Method375 participants from the PREVENT‐Dementia study underwent arterial spin labelling (ASL) and structural 3Tesla MRI. ASL data were analysed using BASIL/FSL and structural scans with SPM12. CBF maps were corrected for partial volume effects. A vascular territory mask with nine territories, the middle, proximal and distal branches of the anterior, middle and posterior cerebral arteries (ACA, MCA, PCA) was used for region‐of‐interest analysis and registered to the native ASL space. Regional gray matter (GM) CBF values were harmonised using COMBAT. Linear regression was used to examine differences between APOE4 carriers and non‐carriers controlling for age, sex and years of education. Associations between haematological properties and CBF were examined with Pearson’s correlations. Differential relationships between CBF, haematocrit, and measures of red blood cell size and shape (distribution width (RDW) and mean corpuscular volume (MCV)) were investigated by including interaction terms of APOE4 and haematological variables in the models.ResultAPOE4 carriers had significantly higher CBF in the proximal MCA (t = 2.54, p = 0.01). Across all subjects, RDW and MCV were not associated with GM CBF, though several significant interactions were observed between APOE4 and RDW in predicting CBF (Figure 1). Haematocrit was associated with GM CBF (ρ = ‐0.19, p &lt; 0.01). No significant interactions were seen between APOE4 and haematocrit or MCV in predicting CBF.ConclusionThe variability of the size and shapes of erythrocytes was differentially associated with CBF between APOE4 carriers and non‐carriers suggesting a different response to morphological erythrocyte alterations. This could further relate to underlying factors such as inflammation, which is associated with a higher RDW. Such associations should be examined in further studies.

Investigating the impact of APOE4 genotype on the association between cerebral blood flow and haematological properties in mid‐life adults

AbstractBackgroundCarriership of the apolipoprotein ε4 (APOE4) allele confers a heightened risk for the development of Alzheimer’s disease (AD). Cerebral blood flow (CBF) is decreased in prodromal and established AD, however findings in the preclinical stage are mixed, with some studies reporting increases. CBF can be impacted by many factors including the haematocrit. We investigated in a cohort at risk of developing AD how haematological variables relate to CBF and if this relationship is differentially moderated by APOE4.Method375 participants from the PREVENT‐Dementia study underwent arterial spin labelling (ASL) and structural 3Tesla MRI. ASL data were analysed using BASIL/FSL and structural scans with SPM12. CBF maps were corrected for partial volume effects. A vascular territory mask with nine territories, the middle, proximal and distal branches of the anterior, middle and posterior cerebral arteries (ACA, MCA, PCA) was used for region‐of‐interest analysis and registered to the native ASL space. Regional gray matter (GM) CBF values were harmonised using COMBAT. Linear regression was used to examine differences between APOE4 carriers and non‐carriers controlling for age, sex and years of education. Associations between haematological properties and CBF were examined with Pearson’s correlations. Differential relationships between CBF, haematocrit, and measures of red blood cell size and shape (distribution width (RDW) and mean corpuscular volume (MCV)) were investigated by including interaction terms of APOE4 and haematological variables in the models.ResultAPOE4 carriers had significantly higher CBF in the proximal MCA (t = 2.54, p = 0.01). Across all subjects, RDW and MCV were not associated with GM CBF, though several significant interactions were observed between APOE4 and RDW in predicting CBF (Figure 1). Haematocrit was associated with GM CBF (ρ = ‐0.19, p &lt; 0.01). No significant interactions were seen between APOE4 and haematocrit or MCV in predicting CBF.ConclusionThe variability of the size and shapes of erythrocytes was differentially associated with CBF between APOE4 carriers and non‐carriers suggesting a different response to morphological erythrocyte alterations. This could further relate to underlying factors such as inflammation, which is associated with a higher RDW. Such associations should be examined in further studies.

Calcium flux alterations in erythrocytes from sickle cell mice: The relevance of mean corpuscular volume

Red blood cells (RBC) from patients with sickle cell disease (SCD) have elevated calcium levels at baseline, which are further elevated upon deoxygenation. Here we examined baseline calcium levels and calcium flux in RBCs from a mouse model of SCD mice. We found that akin to humans with SCD, sickle (HbSS) Townes mice, have higher baseline levels and increased calcium flux in RBCs compared to control (HbAA) animals. As HbSS mice, unlike humans with SCD, have high mean corpuscular volume compared with HbAA, we highlight the importance of adjusting biochemical results to number of RBCs rather than hematocrit during the analysis and interpretation of the results. Our findings add to the face validity of humanized sickle cell mice and support its use for studies of RBC calcium flux in SCD.

A Prospective Study on Haemotological Profile of Sickle Disease

Background: Sickle cell disease (SCD) refers to a category of inherited hemoglobin (Hb) disorders. The pathophysiology of sickle Hb (HbS) variant emerges from the polymerization of the ensuing HbS variant, which triggers a chain of erythrocyte alterations and the disorder is known to be caused by a single-nucleotide substitution at position 6 of the globin gene. Both acute and chronic sequelae cause significant morbidity in people with sickle cell anemia (SCA). Methods: This prospective cross-sectional study was conducted in the Department of Pediatrics and Sickle Cell Anemia Laboratory, Department of Pathology, Prathima institute of medical sciences, Karimnagar India, between June 2019-Feb 2020.Most of patients were from tribal background and lower socioeconomic status. Before conducting the study, permission was obtained from the Ethical Clearance Committee. Results: A total of 37 children’s homozygous (SS) (mean age 11.6±3.4 years) for sickle cell anaemia was studied for their haematological parameters. Out of the total SS subjects, 26 were males and 11 were females. Males to female’s sex ratio: 2.3. 6 years to 14 years of childrens were taken. Mean (SD) age of male was 9.4 (3.29) years whereas SD age of female was 9.59 (3.59) years. Haematological value of study are mentioned below. Conclusion: We conclude that moderate to severe anemia with, lowMCV and high HbF dominate the hematological profile.

Proteome alterations in erythrocytes with PIEZO1 gain-of-function mutations.

Gain-of-function mutations in PIEZO1 cause dehydrated hereditary stomatocytosis (DHS) or hereditary xerocytosis, an autosomal dominant hemolytic anemia characterized by high reticulocyte count, a tendency to macrocytosis, and mild jaundice, as well as by other variably penetrant clinical features, such as perinatal edema, severe thromboembolic complications after splenectomy, and hepatic iron overload. PIEZO1 mutations in DHS lead to slowed inactivation kinetics of the ion channel and/or facilitation of channel opening in response to physiological stimuli. To characterize the alterations of red blood cell proteome in patients with mutated PIEZO1, we used a differential approach to compare the proteome of patients with DHS (16 patients from 13 unrelated ancestries) vs healthy individuals. We identified new components in the regulation of the complex landscape of erythrocytes ion and volume balance mediated by PIEZO1. Specifically, the main impaired processes in patients with DHS were ion homeostasis, transmembrane transport, regulation of vesicle-mediated transport, and the proteasomal catabolic process. Functional assays demonstrated coexpression of PIEZO1 and band 3 when PIEZO1 was activated. Moreover, the alteration of the vesicle-mediated transport was functionally demonstrated by an increased vesiculation rate in patients with DHS compared with healthy controls. This finding also provides an explanation of the pathogenetic mechanism underlying the increased thrombotic rate observed in these patients. Finally, the newly identified proteins, involved in the intracellular signaling pathways altered by PIEZO1 mutations, could be used in the future as potential druggable targets in DHS.

Morphological Alterations of Fish Erythrocytes as Their Response to Environmental Conditions

Fish bodies respond to changes in environmental conditions in various ways and degrees. Seven fish species were collected from three study locations, including two nearshore sites (Ha Tinh province and Nha Trang city, Khanh Hoa province) and one offshore site (Toc Tan island, Khanh Hoa province) to evaluate alterations in erythrocyte morphology under certain environmental conditions. Heavy metal concentrations at all study sites were analyzed and met the acceptable technical criteria for each site. Fish blood samples were taken from the tail veins, anticoagulated with heparin, and stained with Giemsa stain. The blood cell morphological study was performed using an optical microscope. The results revealed two types of morphological abnormalities of fish erythrocytes, including nuclear deformation and nuclear-matter distribution.