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Some risk causes may be associated with the severity of COVID-19. The central host-pathogen factors might affect infection are human receptor angiotensin-converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), and SARS-CoV-2 surface spike (S)-protein. The main purpose of this study was to determine the differences in the expression the metalloproteinases-2 (MMP-2), MMP-9, ACE2, and TMPRSS2 genes and their correlation with lymphopenia in the mild and severe types of the COVID-19 patients. Eighty-eight patients, aged 36 to 60 years old with the mild (n=44) and severe (n=44) types of COVID-19 were enrolled. Total RNA was isolated from the peripheral blood mononuclear cells (PBMCs). The changes of MMP-2, MMP-9, ACE2 and TMPRSS2 gene expression in PBMCs from mild and severe COVID-19 patients were examined by the real time-quantitative polymerase chain reaction (RT-qPCR) assay and, compared between the groups. Data were collected from May 2021 to March 2022. The mean age of the patients in both groups was 48 (interquartile range, 36–60), and there were no appreciable differences in age or gender distribution between the two groups. The present study showed that a significant increase in the expression of ACE2, TMPRSS2, MMP-2, and MMP-9 genes in the severe type of the COVID-19 patients compared, to the mild type of the COVID-19 patients. Overall, it suggests the expression levels of these genes on the PBMC surface in the immune system are susceptible to infection by SARS-COV-2 and therefore could potentially predict the patients’ outcome. [ABSTRACT FROM AUTHOR]

Background: Over the past decades, interest in establishing a National Rare Donor Program has increased significantly worldwide. The experience of developing countries, however, is still limited. Rare blood is defined as a blood group found in a 1000- 5000 population and donor has an absence of a high-prevalence antigen, or the absence of multiple common antigens. Iranian national rare donor program was established in 2009. This paper reports the experiences and challenges of establishing a national rare donor program in Iran. Materials and Methods: This program provides services to all medical centers that need rare units. The main role of rare donor program is to maintain information of rare donors that are identified at the immunohematology reference laboratory located in Tehran. Good manufacturing practices and standard operating procedures are utilized to all activity. The IRL secures frozen blood to make them available when rare blood is required. Results: As many as 1000 different types of rare donors have been identified in Iran, including several individuals whose blood group had developed clinically significant allo-antibodies. In addition to routine donors' personally identifiable information such as addresses and telephone numbers, we also access to the contact information of their close relatives or friends for emergency situation. Contact data are kept up to date at least twice annually. IRL staff are ready to provide services to patients with rare blood types, 24 hours per day, 7 days per week. To date, more than 80 donors with very rare blood group are listed on the IRL rare donor database in 31 centers. Current practice at IRL is to screen the first and second-degree relatives of any patient found to have a rare blood type for a matching blood donor. Iranian blood services need to establish special departments to provide rare blood RBCs and technical assistance for a quicker and more efficient responses to patients and request of their medical staff for blood transfusion. To achieve this aim, there were several challenges, including situation analysis and justification of the program, allocation of financial support by top managers, engineering and technical maintenance, facility and environmental services, employee awareness and communication between blood centers, technologist training in advanced immunohematology. Conclusion: The results of this survey are encouraging and indicate that the information and database for rare donors will provide services to patients with very difficult and complex serology test results requiring rare blood transfusion. The experience of IRL may be helpful for other transfusion centers in developing countries. [ABSTRACT FROM AUTHOR]

Background: Some of the red cell storage lesions (RCSLs) take place during red blood cell (RBC) storage and may reduce the function of these cells dramatically, which mostly caused by residual leucocytes in blood components. This study was planned to observe the biochemical and hematological changes in pre-storage leukoreduced RBC (LR-RBC) compared with unfiltered RBC during in vitro storage. Materials and Methods: Ten unit RBCs were collected, processed and stored according to Iranian standard operating procedure (SOP) of Iranian Blood Transfusion Organization (IBTO). Every unit was split into two equal parts, unfiltered RBC and LR-RBC. Samples were collected and tested on weeks of storage. Biochemical parameters such as lactate dehydrogenase (LDH), lactate concentration and glucose-6-phosphate dehydrogenase (G6PD) enzyme activity were measured by auto-analyzer. In addition, hematology analyzer was used to monitor the change of RBC indices such as (MCV), (MCH) and (MCHC). Results: In this study, both groups showed progressive increase of LDH and lactate levels, and also G6PD activity decreased during storage. Mean of LDH and lactate in unfiltered RBC was significantly increased compared with LR-RBC during all days of storage (p< 0.05). There was statically significant decrease in the G6PD enzyme activity between the two groups and weeks of storage (p< 0.05). However, the RBC indices remained within the expected levels in both groups. Conclusion: LR-RBC and RBC both exhibited RCSL during storage, but LR-RBC is effective in reducing Red cell storage lesion (RCSL) and also improves the quality of stored red blood cells. [ABSTRACT FROM AUTHOR]

Introduction: Alloimmunization is a reaction of the immune system to foreign antigens. For prevention of alloantibody formation, performing of type and screen test is necessary on a patient's blood specimen as part of pre-transfusion testing. Materials and method: In this cross-sectional study, type and screen test done for 1420 patients with elective surgery for detection of alloantibody in Imam Khomeini hospital in Ardabil. Results: Prevalence of alloantibody in this population was 0.92% (13 patients) and 99.2% (1407 patients) showed no alloantibody in their serum. The most prevalent alloantibody was anti-K, anti-E and anti-c. No significant relationship observed between sex and alloimmunization rate. Conclusion: performance of type and screen test play an important role in reducing the rate of alloimmunization, and also, could reduce the demands for blood reservation in hospital blood banks. [ABSTRACT FROM AUTHOR]

Background: Leukemic cell metabolism plays significant roles in their proliferation and survival. These metabolic adaptations are under regulation by different factors. Programmed Death Ligand -1 (CD-274) is one of the immune checkpoint ligands that do not only cause the immune escape of cancer cells, but also have some intracellular effects in these cells. PD-L1 is overexpressed on leukemic stem cells and relates with poor prognosis of AML. In this study, we investigated effects of PD-L1 stimulation on critical metabolic pathways of glucose and fatty acid metabolisms that have important roles in proliferation and survival of leukemic cells. Methods: After confirmation of PD-L1 expression by flow cytometry assay, we used recombinant protein PD-1 for stimulation of the PD-L1 on two AML cell lines, HL-60 and THP-1. Then we examined the effect of PD-L1 stimulation on glucose and fatty acid metabolism in cells at the genomic and metabolomic levels in a time dependent manner. We investigated expression changes of rate limiting enzymes of theses metabolic pathways (G6PD, HK-2, CPT1A, ATGL1 and ACC1) by qRT-PCR and also the relative abundance changes of free fatty acids of medium by GC. Results: We identified a correlation between PD-L1 stimulation and both fatty acid and glucose metabolism. The PD-L1 stimulated cells showed an influence in the pentose phosphate pathway and glycolysis by increasing expression of G6PD and HK-2 (P value = 0.0001). Furthermore, PD-L1 promoted fatty acid β-oxidation by increasing expression of CPT1A (P value = 0.0001), however, their fatty acid synthesis was decreased by reduction of ACC1 expression (P value = 0.0001). Conclusion: We found that PD-L1 can promote proliferation and survival of AML stem cells probably through some metabolic changes in leukemic cells. Pentose phosphate pathway that has a critical role in cell proliferation and fatty acids β-oxidation that promote cell survival, both are increased by PD-L1 stimulation on AML cells. [ABSTRACT FROM AUTHOR]

Programmed death ligand-1 (PD-L1) is a pivotal inhibitory checkpoint ligand known to induce T-cell exhaustion via interaction with the programmed death-1 (PD-1) receptor. Beyond this, PD-L1's intrinsic signaling pathways within cancer cells warrant further exploration. This study aims to elucidate the effect of PD-L1 stimulation on the proliferation, survival, and apoptosis of acute myeloid leukemia (AML) cell lines. Two human AML cell lines, HL-60 and THP-1 were cultured and treated with phorbol 12-myristate 13-acetate (PMA) to induce PD-L1overexpression. Post-treatment PD-L1 expression was confirmed via flow cytometry. Subsequently, cell surface PD-L1 was stimulated using a recombinant PD-1, 24 hours post-PMA treatment. The expression alterations in pivotal genes including BCL2, MKI67, BAX, and CASP3 were monitored using quantitative real-time polymerase chain reaction 24 and 48 hours post-treatment. Additionally, annexin-V through flow cytometry. Findings reveal that PD-L1 stimulation augments AML cell proliferation and survival by enhancing MKI67 and BCL2 expressions while concurrently inhibiting cell apoptosis due to decreased BAX and CASP3 expression following PD-L1 stimulation. Notably, stimulated cells expressed exhibited reduced annexin-V compared to control cells. This study underscores that PD-L1 stimulation fosters AML cell proliferation and survival while impeding cell apoptosis. The results hold potential implications for targeting PD-L1 in AML treatment strategies. [ABSTRACT FROM AUTHOR]

Programmed death 1 (PD-1) has a central role in maintaining T cell tolerance and terminating cellular responses after eliminating antigens. Variation in PD-1 gene products caused by polymorphisms has been linked to several malignancies and autoimmune diseases. However, there is little known about the effects of its single-nucleotide polymorphisms (SNPs) on viral infections, particularly COVID-19. The primary aim of this study was to explore the function of genotypes, alleles, and haplotypes of two SNPs within the programmed cell death protein 1 (PDCD1) gene at PD1.3 G/A and PD1.5 C/T on susceptibility to COVID-19 in an Iranian population. The secondary objective was to evaluate the effects of these SNPs on the outcome of the disease. We got blood samples from COVID-19 patients (n = 195) and healthy subjects (n = 500) for genotypic determination of PD1.3 G/A (rs11568821) and PD1.5 C/T (rs2227981) SNPs, using the polymerase chain reaction-restriction fragment length polymorphism method, and constructed four haplotypes for PDCD1 SNPs. We used Pearson's chi-squared test, Fisher's exact test, and T-test for this study and incorporated effect sizes of odds ratio (OR) and standardized mean difference. The frequency of CT genotype of PD1.5 was meaningfully higher in COVID-19 patients (49.2%) than in healthy subjects (37.4%) (p = 0.005). However, these significant differences were not observed in the frequencies of PD1.3 genotypes between the two groups (p > 0.05). Of all estimated haplotypes for PDCD1, only AT was significantly and largely associated with COVID-19 susceptibility (p = 0.01, OR: 7.79 [95% confidence interval = 1.56–38.79]), however, this finding is inconclusive. In addition, the present study showed that the PD1.3 and PD1.5 SNPs were not associated with the outcome of the disease (p > 0.05). These results may propose that the PD1.5 CT genotype and AT haplotype of PDCD1 indecisively contribute to COVID-19 susceptibility in the Iranian population. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndrome (MDS) holds a unique position among blood cancers, encompassing a spectrum of blood-related disorders marked by impaired maturation of blood cell precursors, bone marrow abnormalities, genetic instability, and a higher likelihood of progressing to acute myeloid leukemia. MicroRNAs (miRNAs), short non-coding RNA molecules typically 18–24 nucleotides in length, are known to regulate gene expression and contribute to various biological processes, including cellular differentiation and programmed cell death. Additionally, miRNAs are involved in many aspects of cancer development, influencing cell growth, transformation, and apoptosis. In this study, we explore the impact of microRNAs on cellular apoptosis in MDS. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a neurodegenerative condition that results in axonal and permanent damage to the central nervous system, necessitating healing owing to autoimmune reactions and persistent neuroinflammation. Antioxidant and anti-inflammatory drugs are essential for the management of oxidative stress and neuroinflammation. Additionally, multivitamin supplementation, particularly vitamin B12 (cobalamin), may be beneficial for neuronal protection. Although there is no documented connection between vitamin B12 deficiency and MS, researchers have explored its potential as a metabolic cause. This review highlights the therapeutic benefits of cobalamin (Cbl) in patients with MS. [ABSTRACT FROM AUTHOR]

Epigenetic alterations could cause leukemia through the activation of normally silent loci or silencing of normally active loci. We herein aimed to compare the expression patterns of a histone modifiers panel consisted of SUV39H1, PRDM16, UHRF2, KDM2B , and KDM3C between acute myeloid leukemia(AML) cells and normal cells and to assess the correlation of these genes with the expression of vital tumor suppressor genes, including p16INK4A and p53. Bone marrow or peripheral blood samples of 50 AML patients at diagnosis and also 18 subjects with a normal hematopoietic system as a control group were obtained after informed consent. Then, qRT-PCR was performed to determine the expression levels of the aforementioned genes. We found a broad alteration in the expression signature of five out of seven studied genes in AML patients as compared with the control group. UHRF2 and p53 were remarkably downregulated in AML patients (P <0.001), while SUV39H1, PRDM16, and KDM3C were significantly overexpressed (P <0.01). Based on the Spearman rank correlation, SUV39H1 and KDM2B negatively regulated both p16INK4A and p53 expression. Taken together, our findings provided preliminary evidence regarding the pervasive mRNA perturbation of histone modifiers and their plausible influences on critical tumor suppressor genes. Future studies in this area would be required to assist in establishing these results in the clinical practice of AML patients. [ABSTRACT FROM AUTHOR]