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Anticipation of Relapse and Acute Graft-Versus-Host Disease after Allogeneic Peripheral Blood Stem Cell Transplantation: The Fundamental Role of Antigen-Presenting (Dendritic) Cells

Research Abstract

Background

Dendritic cells (DCs) are antigen-presenting cells. In humans two distinct lineages of DCs exist: DC1 and DC2. Efforts to explore the role of DCs in acute graft-versus-host disease (aGVHD) after allogeneic peripheral blood stem–cell transplantation (PBSCT) are gaining traction. However, further research is needed to identify particular lineages and their values in terms of developing an evidence-based aGVHD- or relapse-prevention strategy. We monitored DC counts and subsets in PBSC grafts while harvesting stem cells in recipients to elucidate their value in anticipating disease relapse or aGVHD.

Methods

We enrolled 29 participants. Using fluorescence-activated cell sorting, total counts/kg of CD34+, DCs, and DC subsets were analyzed in 29 PBSC-graft components using CMRF44, CD11c, and CD4 monoclonal antibodies (MoAbs).

Results

In the 29 grafts, we detected a significant positive correlation (P<0.01) between DCs and both DC1 and DC2. Significantly higher counts (P<0.01) of DCs and DC1 in those who had developed aGVHD (nine cases) were also observed. Relapsed cases (two) were also associated with higher counts of DCs and DC2. A significant positive correlation (P<0.05), was recorded between DCs and DC1 counts and the day of myeloid engraftment, while this was not detected on the day of platelet engraftment. Myeloid engraftment transpired earlier in patients without aGVHD. Increased DC-graft numbers, particularly DC1 measured by CD11c Moabs, were associated with aGVHD. Recipients of higher numbers of CD4bright DCs had an increased risk of relapse after allogeneic PBSCT.

Conclusion

This study analyzed DCs in PBSC grafts, using novel specific MoAbs and flow cytometry. Our data showed that higher donor DC1 counts were linked to the incidence of aGVHD and DC2 with relapse. We propose a fundamental role for DC-graft monitoring in anticipating aGVHD and disease relapse.

Research Authors
Khalid Ali Nasif, Awad S Al Samghan, Nahla El-Sharkawy, Amr M Abass, Ebtesam Elgezawy, Safaa AA Khaled, Mahmoud I Elbadry, Marwa M Thabet
Research Date
Research Department
Research Journal
Journal of Inflammation research
Research Pages
3733-3747
Research Publisher
Taylor and Francis
Research Vol
23(3)
Research Website
https://www.tandfonline.com/doi/full/10.2147/JIR.S366619
Research Year
2022

Significance of the mathematically calculated red cell indices in patients with qualitative and quantitative hemoglobinopathies

Research Abstract

Background

Hemoglobinopathies represent a set of inherited red blood cell (RBCs) disorders, characterized by abnormal hemoglobin molecule. They include qualitative and quantitative hemoglobinopathies, with a structurally abnormal globin chain in the first and defective production in the later. This study assessed, for the first time, the significance of the mathematically calculated RBC indices to identify patients with hemoglobinopathies from normal subjects or iron deficiency anemia (IDA) and to differentiate various types of hemoglobinopathies from each other.

Subjects and methods

The study was a comparative hospital based and included 167 participants with hemoglobinopathies (group 1) and 49 participants with IDA (group 2) as an active comparator. Another 50 healthy volunteers (group 3) were also included. All participants were subjected to medical history, clinical examination, CBC, and HPLC. Next, 10 RBC indices were mathematically calculated from the CBC for each participant.

Results

Gender analysis shows that females represent 36.8% in thalassemia group, 42% in sickle cell disease (SCD) group, and 71.4% in IDA group. The receiver operating characteristic (ROC) curve shows that Ehsani index (EI) is the most reliable screening tool for thalassemics because of showing the highest Youden index and specificity of 41.88% and 88.89%, respectively, followed by Shine and Lal index (SL), with Youden index (YI) value, specificity, and sensitivity equal to 39.78%, 69.70%, and 70.09%, respectively. Similar results were found for IDA. For SCD, SL index is the most suitable screening tool. In conclusion, the mathematically calculated RBC indices are available, cheap, reliable, and sensitive tools for screening patients with hemoglobinopathies.

Research Authors
Heba A Ahmed, Safaa AA Khaled, Eman M Fahmy, Nesreen A Mohammed, Hamdy FF Mahmoud
Research Date
Research Department
Research Journal
The Egyptian Journal of Internal Medicine
Research Pages
60
Research Publisher
Springer Berlin Heidelberg
Research Vol
34 (!)
Research Website
https://link.springer.com/journal/43162
Research Year
2022

Hematological, Biochemical Properties, and Clinical Correlates of Hemoglobin S Variant Disorder: A New Insight Into Sickle Cell Trait

Research Abstract

Background

The sickle cell trait (SCT) disorder possesses a clinical heterogeneity ranging from a symptomless condition to sudden death. This study aimed to develop a diagnostic approach that helps the characterization and identification of SCT from normal subjects and sickle cell disease (SCD) patients, and to assess its severity.

Methods

Sixty controls, 24 SCD patients and 31 SCT subjects were assessed clinically, radiologically and by laboratory investigations.

Results

Of the SCT subjects, 12.8% were symptomatic (3.2% anemic, 6.4% hemolytic crisis, and 3.2% painful crises). Anemia was normocytic in 66.6%, and normochromic and polychromatic in 33.4%. Significantly lower red blood cells (RBCs), hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), hematocrit (Hct), Shine and Lal index (SL), and hemoglobin A (Hb A), and higher mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), Ricerca index (RI), and Huber-Herklotz index (HH) were found in SCT subjects compared with the controls. Hb A and hemoglobin S (Hb S) were excellent in discriminating SCT from SCD (cut-off for SCT > 50% and < 40%) followed by Hct, MCHC, Hb, Green and King index (GK), and England and Fraser index (EF) (cut-off for SCT > 33%, > 32, > 11, < 71, and < 10, respectively). Radiologically normal findings were detected in 87% of SCT subjects; they had nearly normal liver and renal function tests (except one case each). A schematic diagnostic paradigm for SCT was proposed.

Research Authors
Safaa AA Khaled, Heba A Ahmed, Mahmoud I Elbadry, Eman NasrEldin, Sahar M Hassany, Shimaa A Ahmed
Research Date
Research Department
Research Journal
Journal of hematology
Research Pages
94
Research Publisher
Elmer Press
Research Vol
11(3)
Research Website
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9275442/
Research Year
2022

Drug therapy in patients with severe forms of sickle cell anemia: A nonrandomized clinical trial of combining l-carnitine with hydroxycarbamide therapy

Research Abstract

Abstract: BACKGROUND AND AIM: Combining Hydroxycarbamide (hydroxyurea) therapy and L-Carnitine (HU+LC) was proved effective and tolerable in patients with thalassemia intermedia; however, its role in sickle cell anemia (SCA) was not investigated. This study aimed to assess various aspects of treatment with HU + LC in adult patients with severe forms of SCA. PATIENTS AND METHODS: Ninety‑one adult SCA patients were recruited, then distributed into four treatment groups: Group 1 – 37 patients treated with HU + LC; Group 2 – 16 patients treated with HU; Group 3 – 18 patients treated with LC; and Group 4 – 20 patients received supportive treatment only. Their baseline data were recorded then reassessed 8–12 weeks later. Their compliance was assessed subjectively. RESULTS: Patients were nearly matched as regards gender, age, baseline hematologic, and biochemical data. Compared to baseline, HU + LC treatment significantly increased hemoglobin and reduced reticulocytes, white blood cells, mean corpuscular hemoglobin concentration, and lactate dehydrogenase (LDH). Compared with other lines, HU + LC significantly reduced number of painful episodes, blood transfusions, and in hospital days per year. Adding LC to HU improved patient compliance, with mild side effects. Residence, side effects, baseline hemoglobin (Hb), and Hb F% affected patients’ compliance. Both gender and age did not show any influence on response to treatment while side effects, compliance, baseline Hb, and LDH displayed a significant effect. CONCLUSION: Combining LC with HU for the treatment of adult SCA patients showed superior hematologic and clinical effectiveness. The response was more obvious in severe cases. However, health education about the combination is needed to improve patients’ compliance and therapeutic responses. Trial registration: Clinical Trials.gov, NCT05081349. https://clinicaltrials.gov/ct2/show/NCT05081349. Keywords: Hydroxycarbamide, L‑carnitine, sickle cell anemia, severe forms

Research Authors
Safaa A A Khaled and Esraa M Ashry
Research Date
Research Department
Research Journal
Journal of Applied Hematology
Research Pages
237-248
Research Publisher
Medknow
Research Vol
13(4)
Research Website
https://journals.lww.com/jaht/_layouts/15/oaks.journals/downloadpdf.aspx?an=01797455-202213040-00011
Research Year
2022

Heavy metal levels are positively associated with serum periostin and miRNA-125b levels, but inversely associated with miRNA-26a levels in pediatric asthma cases. A case-control study

Research Abstract

Background

The study investigated heavy metals levels [urinary cadmium (U-Cd), erythrocytic cadmium (E-Cd), urinary arsenic (U-As), and whole blood lead (WB-Pb)] in children with bronchial asthma (BA) and tested their associations with serum periostin, miRNA-125b and miRNA-26a levels, and with asthma severity clinically and laboratory [blood eosinophils count (BEC) and serum total immunoglobin E (IgE)]. Also, we tested cut-off points, for the studied parameters, to distinguish BA cases from healthy children.

Methods

This case-control study included 158 children divided into control group; n = 72 and BA group; n = 86. Heavy metals were measured by an inductively coupled plasma-optical emission spectrophotometer. Serum periostin and IgE levels were measured by their corresponding ELISA kitsmiRNAs relative expressions were estimated by RT-qPCR using the 2-ΔΔCT method.

Results

Heavy metals, serum periostin, and miR-125b levels were significantly high in BA group (p < 0.001). Heavy metals levels correlated positively with serum periostin, miR-125b and IgE levels, BEC, and asthma severity. The reverse was observed regarding serum miR-26a levels. Receiver operating characteristics (ROC) curve analysis showed good to excellent abilities of U-Cd, E-Cd, U-As, WB-Pb, serum periostin, miRNA-125b, and miRNA − 26a, and total IgE levels to distinguish BA cases from healthy children.

Conclusions

Heavy metal toxicity in children is associated with BA severity, increased serum periostin and miRNA-125b levels, and decreased miRNA-26a levels. Specific measures to reduce children's exposure to heavy metals should be taken. Future research should consider blocking miRNA-125b action or enhancing miRNA-26a action to manage BA cases.

Research Authors
Khalid M. Mohany , Yasser Gamal b, Yaser F. Abdel Raheem
Research Date
Research Department
Research Journal
Journal of Trace Elements in Medicine and Biology

Pigment epithelium-derived factor (PEDF) represses the glucose transporter 1 (GLUT1) mRNA expression and may be a potential therapeutic agent in psoriasis: a case–control and experimental study

Research Abstract

We investigated the whole blood GLUT1 mRNA expression and serum pigment epithelium-derived factor (PEDF), interleukin-6 (IL-6), fetuin-A, and pentraxin-3 (PTX3) levels in psoriatic patients and tested their correlations with the severity of psoriasis using the psoriasis area and severity index (PASI) score. Also, we tested the GLUT1 mRNA expression after an in vitro treatment of human skin fibroblast (HSF) cell lines with PEDF. The case–control part of the study recruited 74 participants (44 psoriatic patients and 30 healthy volunteers). Whole blood GLUT1 mRNA fold changes were estimated by RT-PCR, and serum PEDF, IL-6, fetuin-A, and PTX3 levels were measured by ELISA kits. In the experimental part, the HSF cell lines were treated with different concentrations of PEDF for different times to test its effect on the GLUT1 mRNA expression. The whole blood GLUT 1 expression significantly increased in psoriatic patients and correlated positively with serum IL-6, fetuin-A, PTX3 levels and with the severity of psoriasis while negatively with serum PEDF levels. The PEDF-treated HSF cell lines showed a time- and dose-dependent decline in the GLUT 1 mRNA expression. The whole blood GLUT 1 mRNA is a non-invasive biomarker that is associated with the severity of psoriasis. PEDF represses GLUT 1 expression and may be a potential therapeutic agent in psoriasis.

Research Authors
Khalid M. Mohany, Sherouk Elkady, Eman M. Kamal Youssef, Noorhan M. Sayed & Naglaa Kamal Idriss
Research Date
Research Department
Research Journal
Scientific Reports

Nano ciprofloxacin/meropenem exhibit bactericidal activity against Gram-negative bacteria and rescue septic rat model

Research Authors
Safy Hadiya , Reham A Ibrahem , Rehab M Abd El-Baky , Mahmoud Elsabahy , Abeer MR Hussein , Mohammed EM Tolba & Sherine A Aly
Research Date
Research Journal
Nanomedicine
Research Year
2023

Therapeutic Potential of Human Mesenchymal Stem Cells Engineered with Different Concentrations of TNFα and IFNg

Research Abstract

Aims: In this study, the authors aimed to examine the functional activities (adhesion, proliferation, and migration) of hMSCs under the effects of various concentrations of inflammatory mediators, such as TNFα or IFNg. Methods: HMSCs were exposed to various concentrations of the inflammatory mediators TNFα or IFNg, and the effects of TNFα or IFNg on the functional properties of hMSCs were determined using multiple functional assays (adhesion, proliferation, and migration). HMSC expression of genes (cytokine, chemokine, and adhesion molecule genes) was analyzed using real-time polymerase chain reaction (RT–PCR). Results: TNFα promoted their proliferation and migration especially at 100 ng/ml, while IFNg increased proliferation only at concentrations of 10 ng/ml and proliferation at 50 and 100 ng/ml. Conclusion: This study evaluated the suitability of hMSCs in treating inflammatory diseases, which are characterized by high levels of inflammatory mediators such as TNFα or IFNg, and proved that the treatment of hMSCs with TNFα or IFNg at higher concentrations has a protective effect.

Research Authors
logo Therapeutic Potential of Human Mesenchymal Stem Cells Engineered Alsharidah, Mansour 1 ; Elsafadi, Mona 2 ; Al Rugaie, Osamah 3 ; Mahmood, Amer 2 ;
Research Date
Research Department
Research Journal
Journal of Biomaterials and Tissue Engineering

Detection of multiple extensively-drug resistant hypervirulent Klebsiella pneumoniae clones from patients with ventilator-associated pneumonia egypt

Research Abstract

Introduction. Hypervirulent-K. pneumoniae (hvKP) is an evolving pathotype that is more virulent than the classical-K. pneumoniae (cKP) and causes serious fatal illnesses.

Hypothesis/Gap Statement. Although there are few reports on hvKP isolated from Egyptian patients, the molecular characteristics and clonal relatedness of MDR-hvKP have not been adequately investigated.

Aim. To investigate the microbiological and genetic characteristics as well as the epidemiology of hvKP induced ventilator-associated pneumonia (VAP).

Methodology. A retrospective study of 59 Kpneumoniae inducing VAP was conducted at Assiut University Hospitals from November 2017 to January 2019. All K. pneumoniae were tested for resistance phenotype, capsular genotype (K1 and K2), virulence gene profile (c-rmpA, p-rmpA, iucA, kfu, iroB, iroN), and the presence of resistance genes (blaNDM-1, blaCTX-M-3-like, blaCTX-M-14-like …

Research Authors
Hadeel Elzeny1​, Wegdan Mohamed2​, Enas Daef2​, Omnia El-Badawy2​, Lamiaa Shaaban3​, Naglaa S. Osman4​, Safy Hadiya1​ and Sherine Aly2​ORCID icon
Research Date
Research Journal
Journal of Medical Microbiology
Research Pages
001701
Research Publisher
Microbiology Society
Research Vol
Volume 72, Issue 6
Research Website
https://scholar.google.com.eg/scholar?oi=bibs&cluster=13956000809166275176&btnI=1&hl=en
Research Year
2023

Detection of multiple extensively-drug resistant hypervirulent Klebsiella pneumoniae clones from patients with ventilator-associated pneumonia in Egypt No Access

Research Abstract

Introduction. Hypervirulent-K. pneumoniae (hvKP) is an evolving pathotype that is more virulent than the classical- K. pneumoniae (cKP) and causes serious fatal illnesses.

Hypothesis/Gap Statement. Although there are few reports on hvKP isolated from Egyptian patients, the molecular characteristics and clonal relatedness of MDR-hvKP have not been adequately investigated.

Aim. To investigate the microbiological and genetic characteristics as well as the epidemiology of hvKP induced ventilator-associated pneumonia (VAP).

Methodology. A retrospective study of 59 K . pneumoniae inducing VAP was conducted at Assiut University Hospitals from November 2017 to January 2019. All K. pneumoniae were tested for resistance phenotype, capsular genotype (K1 and K2), virulence gene profile (c-rmpA, p-rmpA, iucA, kfu, iroB, iroN), and the presence of resistance genes (blaNDM-1, blaCTX-M-3-like, blaCTX-M-14-like). Clonal relatedness was assessed by Pulsed field gel electrophoresis (PFGE).

Result. HvKP accounted for 89.8 % (53/59) of K. pneumoniae isolates with ~95 % exhibiting extensively-drug resistant (XDR) phenotype. Hypermucoviscous phenotype was detected in 19 (35.8 %) hvKP and K2 capsular gene was identified in 18 (33.9 %) of hvKP. Regarding the virulence genotype of hvKP strains, iucA was the most prevalent virulence gene (98.1%), while p-rmpA and kfu were detected in 75.4 and 52.8 % of hvKP strains, respectively. Resistance genes were highly prevalent in both cKP and hvKP with blaCTX-M-3-like being more prevalent in hvKP (100 % vs 94.3 % for blaNDM-1, 50 % vs 62.2 % for blaCTX-M-3- like and 83.3 % vs 69.8 % for blaCTX-M-14 -like, respectively). PFGE typing of 29 representative K. pneumoniae revealed 15 pulsotypes, with identical hvKP pulsotypes isolated from different ICUs at different times and several hvKP and cKP isolates belonged to the same pulsotype.

Conclusion. This study highlights the dominance and clonal spread of XDR-hvKP strains at Assiut University Hospital in Egypt. Physicians should be aware of the increased risk of hvKP induced-VAP and support further epidemiologic stu

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Research Authors
Hadeel Elzeny1​, Wegdan Mohamed2​, Enas Daef2​, Omnia El-Badawy2​, Lamiaa Shaaban3​, Naglaa S. Osman4​, Safy Hadiya1​ and Sherine Aly2​ORCID icon
Research Date
Research Journal
Journal of medical microbiology
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