International Journal of Hematology-Oncology and Stem Cell Research

Assessment of Torque Teno Virus (TTV) Frequency in Healthy Blood Donors in the Central Region of Iran, Yazd

Sun, 21 Apr 2024 12:11:54 +0000

Background: Torque teno virus (TTV) is a globally prevalent virus in humans, yet comprehensive knowledge about its prevalence, predominant transmission routes, and pathogenesis remains limited. This study aimed to assess the frequency of TTV infection among healthy blood donors in Yazd, Iran.

Materials and Methods: A total of 236 healthy blood donors, devoid of HIV/HBV/HCV infection markers, participated in the study from 2015 to 2016. Nested Polymerase Chain Reaction (PCR) utilizing a set of oligo primers for the 5΄- UTR region was employed to detect TTV DNA in serum samples.

Results: The TTV genome was identified in 161 out of 236 (61.2%) healthy blood donors. The mean age for men and women was 43 and 57 years, respectively. Of the participants, 156 were male, and 107 were female. Donor age exhibited a significant association with virus presence (P=0.007); however, gender did not show a statistically significant association with the frequency of TTV infection in healthy blood donors (P=0.3).

Conclusion: The study revealed a notably high frequency of the Torque teno virus in Yazd province, aligning with similar findings globally. Further investigations are warranted to elucidate the clinical implications of the virus in the healthy population.

Influence of Different Glucose Concentrations on the Expression of miR-29c-3p microRNA in Mesenchymal Stem Cells

Somayeh Mansournejad, Mohammadreza Mehrabi, Reza Yari, Mahshid Saleh — Sun, 21 Apr 2024 12:18:09 +0000

Background: miR-29c-3p manages a set of genes involved in regenerative medicine, and It seems that hyperglycemia in diabetic patients influences the power of stem cells to tissue regeneration the difficulties of diabetes by affecting the expression miR-29c-3p in mesenchymal stem cells. The study aims to analyze the effect of various glucose concentrations on the miR-29c-3p expression in mesenchymal stem cells.

Materials and Methods: After receiving donated mesenchymal stem cells from Tarbiat Modares University, these cells were cultivated in a DMEM culture medium, including three different concentrations of glucose 250, 140, and 100 mg/dl. RNA was extracted from these cells after 72 hours, the Real-Time PCR technique assessed the expression of miR-29c-3p, and the results were analyzed by REST software.

Results: miR-29c-3p expression in cells at concentrations of 140 and 250 mg/dL compared to typical situations (100 mg/dl) was significantly decreased (P˂0.05), which declined at a concentration of 250 mg/dl was more.

Conclusion: Reduced miR-29c-3p expression in mesenchymal stem cells in chronic and mild diabetic situations demonstrated that diabetes might be one of the significant reasons for mesenchymal stem cells' reduced ability to repair tissue damage.

Antileukemia Activity of Human Natural Killer Cell-Derived Nanomagic Bullets against Acute Myeloid Leukemia (AML)

Sun, 21 Apr 2024 12:25:21 +0000

Background: Cancer is among the serious health problems of the medical world, for treatment of which severe treatments are used. However, the prognosis of cancer patients is still poor. The application of NK cell-derived exosomes (NK-Exo) is a new method for cancer immunotherapy. These nanoparticles with a size range of 30-120 nm are a small model of mother cells. In this study, the anti-tumor activity of NK-Exo and LAK-Exo (activated NK cell-derived exosome) against acute myeloid leukemia (AML) is investigated in vitro.

Materials and Methods: The MACS method was performed for the separation of NK cells from the buffy coats of healthy donors, and an EXOCIBE kit was used for the isolation of NK-Exo. After treating the KG-1 cell line with different doses of NK-Exo, MTT assay, and annexin V-PE were done to evaluate cell proliferation and apoptosis, respectively, and for confirmation of involved proteins, Real-Time PCR and western blotting were performed.

Results: Anti-tumor activity of NK-Exo and LAK-Exo was dose- and time-dependent. Their highest activities were observed following 48 hours of incubation with 50 µg/ml exosome (p<0.0001). However, this cytotoxic activity was also seen over a short period of time with low concentrations of NK-Exo (p<0.05) and LAK-Exo (p<0.001).The cytotoxic effect of LAK-Exo on target cells was significantly higher than NK-EXO. The induction of apoptosis by different pathways was time-point dependent. Total apoptosis was 34.56% and 51.6% after 48 hours of tumor cell coculture with 50µg/ml NK-Exo and LAK-Exo, respectively. Significant expression of CASPASE3, P38, and CYTOCHROME C genes was observed in the cells treated with 50 µg/ml NK-Exo and LAK-Exo.

Conclusion: Our study confirmed the antileukemia activity of NK-Exo against AML tumor cells in vitro. Therefore, NK-Exo can be considered as a promising and effective treatment for leukemia therapy.

Serum Interleukin 6 (IL -6) as Prognostic Marker in Egyptian CLL patients

Sun, 21 Apr 2024 12:56:32 +0000

Background: Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. Currently, several biomarkers are being used as CLL prognosticators, including elevated protein levels, elevated RNA levels, gene mutations, and epigenetic changes.

Materials and Methods: This study is a prospective study conducted on 55 patients newly diagnosed with CLL, serum IL-6 level was measured initially and after a 6-month treatment course. Correlation with the course of the disease and the known CLL prognostic parameters was done initially and after 6 months.

Results: The initial serum IL-6 level in the patient group (pre-treatment) ranges from 36-91 pg/mL (median 57), and in the patient group (post-treatment) ranges from 1-32 pg/mL (median 2). Serum IL-6 level was positively correlated with WBC count, β2 microglobulin, LDH, ESR, B symptoms, Uric Acid, BM Aspirate (% of lymphocytes), and Binet and Rai staging systems.

Conclusion: Serum IL-6 is a useful poor prognostic marker in newly diagnosed CLL patients; its prognostic value goes with the other known prognostic markers such as the BM lymphocyte count, ESR, and LDH.

Risk of Sarcopenia Identified by Sarc-Calf, Nutritional Status and Hand Grip Strength in Patients with Hematological Cancer

Sun, 21 Apr 2024 13:13:53 +0000

Background: Hematological cancer patients are prone to the development of sarcopenia and impaired nutritional and functional status. SARC-CalF is a screening tool for the risk of sarcopenia that has shown good results in this population. This study aimed to identify the risk of sarcopenia by SARC-CalF and to verify its association with nutritional status and Hand Grip Strength (HGS) in patients with hematological cancer.

Materials and Methods: Adult patients, of both sexes, with hematological cancer, and in outpatient care participated in the study. We measured the Hand Grip Strength of the Dominant Hand (HGSD) and the Adductor Pollicis Muscle Thickness of the Dominant Hand (APMTD). Moreover, we applied the Patient-Generated Subjective Global Assessment (PG-SGA) and SARC-CalF. Data were analyzed with SPSS® software, 22.0, with a significance level of 5.0%.

Results: Fifty-one patients aged an average of 60.4 ± 15.1 years were evaluated. Of those, 58.8% were elderly, 51% female, and 80.4% declared themselves non-white. The predominant diagnosis was Mature B Lymphoid Cell Neoplasia (37.7%), and 60.8% of the patients had a diagnosis time of ≤ 3 years. PG-SGA revealed that 35.3% of the patients were malnourished; APMTD and HGSD revealed that 60.8% and 25.5% had reduced muscle strength, respectively. SARC-CalF exposed that 39.2% of the patients were at risk for sarcopenia. Significant associations were found between SARC-CalF and diagnosis time ≤ 3 years (p = 0.039), PG-SGA (p = 0.020), APMTD (p = 0.039) and HGSD (p = 0.002). After binary logistic regression adjusted for age and sex, the reduced HGSD remained associated with the risk of sarcopenia.

Conclusion: SARC-CalF identified a risk of sarcopenia in 39.2% of patients. The reduced HGSD was associated with the risk of sarcopenia.

Potential Diagnostic Value of Abnormal Pyroptosis Genes Expression in Myelodysplastic Syndromes (MDS): A Primary Observational Cohort Study

Sun, 21 Apr 2024 13:19:55 +0000

Background: Myelodysplastic syndromes (MDS) are determined by ineffective hematopoiesis and bone marrow cytological dysplasia with somatic gene mutations and chromosomal abnormalities. Accumulating evidence has revealed the pivotal role of NLRP3 inflammasome activation and pyroptotic cell death in the pathogenesis of MDS. Although MDS can be diagnosed with a variety of morphologic and cytogenetic tests, most of these tests have limitations or problems in practice.

Materials and Methods: In the present study, we evaluated the expression of genes that form the inflammasome (NLRP3, ASC, and CASP1) in bone marrow specimens of MDS patients and compared the results with those of other leukemias to evaluate their diagnostic value for MDS.

Primary samples of this observational cohort study were collected from aspiration samples of patients with myelodysplastic syndromes (27 cases) and patients with non-myelodysplastic syndrome hematological cancers (45 cases). After RNA extraction and c.DNA synthesis, candidate transcripts and housekeeping transcripts were measured by real-time PCR method (SYBER Green assay). Using Kruskal-Wallis the relative gene expressions were compared and differences with p value less than 0.05 were considered as significant. Discrimination capability, cut-off, and area under curve (AUC) of all markers were analyzed with recessive operation curve (ROC) analysis.

Results: We found that Caspase-1 and ASC genes expressed at more levels in MDS specimens compared to non-MDS hematological malignancies. A relative average expression of 10.22 with a p-value of 0.001 and 1.86 with p=0.019 was detected for Caspase-1 and ASC, respectively. ROC curve analysis shows an AUC of 0.739 with p=0.0001 for Caspase-1 and an AUC of 0.665 with p=0.0139 for ASC to MDS discrimination.

Conclusion: Our results show that Caspase-1 and ASC gene expression levels can be used as potential biomarkers for MDS diagnosis. Prospective studies with large sample numbers are suggested.

Effect of Melissa officinalis on Chemotherapy-Induced Peripheral Neuropathy in Cancer Patients: A Randomized Trial

Sun, 21 Apr 2024 13:24:42 +0000

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a significant cancer treatment side effect that can influence both quality of life and treatment course. Melissa Officinalis (MO), due to its high content of flavonoids, has antioxidant, anti-inflammatory, and neuroprotective properties.

Materials and Methods: The cancer patients diagnosed with CIPN attended a referral center in Sari (Iran). The hydroalcoholic extract of MO leaves was extracted by the maceration method. The control group received a placebo along with gabapentin as the standard treatment, and the intervention group received 500 mg Melissa officinalis 2 times daily for 3 months plus gabapentin. Patients were evaluated at the baseline and 3 months later, according to Common Terminology Criteria for Adverse Effects (CTCAE) and EORTC QLQ-C30 (Integrated System for Quality of Life Assessment).

Results: A total of 40 patients were considered as group D (intervention group), and 35 patients completed the study. Out of 40 subjects in the placebo group (P), 3 patients could not tolerate the drug due to gastrointestinal disturbances. The final values of CTCAE showed a statistically significant difference (p=0.010). Indicators related to the quality of life in both groups showed a significant improvement. In the intervention group, the pain perception and diarrhea experience were significantly reduced.

Conclusion: Quality of life indicators were improved by prescribing gabapentin with and without Melissa officinalis. The addition of Melissa officinalis to the chemotherapy regimen may improve diarrhea and pain perception.

Silibinin, Synergistically Enhances Vinblastine-Mediated Apoptosis in Triple Negative Breast Cancer Cell Line: Involvement of Bcl2/Bax and Caspase-3 Pathway

Wed, 24 Apr 2024 03:34:57 +0000

Background: Triple-negative breast cancer (TNBC) with a poor prognosis and survival is the most invasive subtype of breast cancer. Usually, TNBC requires a chemotherapy regimen at all stages, but chemotherapy drugs have shown many side effects. We assumed that combination therapy of vinblastine and silibinin might reduce the vinblastine toxicity and dose of vinblastine.

Materials and Methods: The MDA-MB-231 were cells subjected to MTT assay for IC50 determination and combination effects, which were measured based on Chou-Talalay's method. The type of cell death was determined by using a Flow-cytometric assay. Cell death pathway markers, including Bcl-2, Bax, and caspase-3 were analyzed by western blot and Real-Time PCR.

Results: The treatment of MDA-MB-231 cells exhibited IC50 and synergism at the combination of 30 µM of silibinin and 4 µm of vinblastine in cell viability assay (CI=0.69). YO-PRO-1/PI double staining results showed a significant induction of apoptosis when MDA-MB-231 cells were treated with a silibinin and vinblastine combination (p<0.01). Protein levels of Bax and cleaved caspase-3 were significantly upregulated, and Bcl-2 downregulated significantly. Significant upregulation of Bax (2.96-fold) and caspase-3 (3.46-fold) while Bcl-2 was downregulated by 2-fold.

Conclusion: Findings established a preclinical rationale for the combination of silibinin and vinblastine. This combination produces synergistic effects in MDA-MB-231 cells by altering pro- and anti-apoptotic genes, which may reduce the toxicity and side effects of vinblastine.

Hemoglobin C Disorder in Anemic Patients Referred to the National Center for Thalassemia and Genetic Counseling in Damascus

Wed, 24 Apr 2024 03:42:35 +0000

Background: Hemoglobinopathies are common inherited blood disorders in our Mediterranean area. The main structural hemoglobin variants are hemoglobin S and hemoglobin C, due to their prevalence.

We conducted this retrospective study to investigate and characterize hemoglobin C patients referred to the National Center for Thalassemia and Genetic Counseling and the management of hemoglobin C disease in Damascus.

Materials and Methods: The study included patients referred to the National Center for Thalassemia and Genetic Counseling in Damascus between 2000 and 2022 for hemoglobin C detection. Gender, age, geographical origin, hemoglobin electrophoresis profile, and blood transfusion were considered for hemoglobin C patient classification. Blood transfusion in five consecutive years and linear regression with hemoglobin S and C values were determined.

Results: 30 (14 males and 16 females) out of 624 patients between 3 and 46 years old (mean ± SD: 17.3 ± 9.7 years) showed hemoglobin C disease. Only eight patients (one male and seven females) received blood transfusions, and the remaining patients (13 males and 9 females) did not receive any transfusion. Only one patient with 100% hemoglobin C was detected; 19 showed HbSC, and 10 had HbAC. There was a significant correlation between hemoglobin S and geographical origin (P-value=0).

Conclusion: A Homozygote hemoglobin C patient has mild hemolytic anemia, whereas the hemoglobin C 100% patient has only a one-time blood transfusion (he was 17 years old) in our study. The inherited combination of hemoglobin C and S is less severe than hemoglobin S alone. There is a significant relationship between hemoglobin S and geographical origin (p-value=0).

Gut Microbiota Composition Correlates with Disease Severity in Myelodysplastic Syndrome

Wed, 24 Apr 2024 03:52:23 +0000

The myelodysplastic syndrome (MDS) is a heterogeneous group of clonal disorders of hematopoietic progenitor cells related to ineffective hematopoiesis and an increased risk of transformation to acute myelogenous leukemia. MDS is divided into categories, namely lineage dysplasia (MDS-SLD), MDS with ring sideroblasts (MDS-RS), MDS with multilineage dysplasia (MDS-MLD), MDS with excess blasts (MDS-EB). The International Prognostic Classification System (IPSS) ranks the patients as very low, low, intermediate, high, and very high based on disease evolution and survival rates. Evidence points to toll-like receptor (TLR) abnormal signaling as an underlying mechanism of this disease, providing a link between MDS and immune dysfunction. Microbial signals, such as lipopolysaccharides from gram-negative bacteria, can activate or suppress TLRs. Therefore, we hypothesized that MDS patients present gut microbiota alterations associated with disease subtypes and prognosis. To test this hypothesis, we sequenced the 16S rRNA gene from fecal samples of 30 MDS patients and 16 healthy elderly controls. We observed a negative correlation between Prevotella spp. and Akkermansia spp. in MDS patients compared with the control group. High-risk patients presented a significant increase in the genus Prevotella spp. compared to the other risk categories. There was a significant reduction in the abundance of the genus Akkermansia spp. in high-risk patients compared with low- and intermediate-risk. There was a significant decrease in the genus Ruminococcus spp. in MDS-EB patients compared with controls. Our findings show a new association between gut dysbiosis and higher-risk MDS, with a predominance of gram-negative bacteria.

HHV-8 Linked to Kaposi's Sarcoma and Castleman's Disease in HIV-1-infected patient: Case Report and Review of the Literature

Aida Zaghdoudi, Hajer Harrabi, Hanene Tiouiri Benaissa — Wed, 24 Apr 2024 00:00:00 +0000

Kaposi’s sarcoma (KS) and multicentric Castleman's disease (MCD) are both linked to human herpesvirus-8 (HHV-8) infection which most commonly affects people living with human immunodeficiency virus (HIV). Herein, we describe the case of a 57-year-old patient who has been admitted for fever, night sweats, weight loss, and diffuse lymphadenopathy with abdominal pain. HIV status was confirmed by a positive Western blot test. His initial CD4 cell count was equal to 270 cells/µL. A histological study of a peripheral lymph node concluded that KS is associated with MCD. These two conditions found in the same patient highlight the malignant potential of HHV-8, particularly in the case of HIV-induced immunodeficiency.

A Case of Deep Venous Thrombosis in an HIV-Infected Patient despite Therapeutic Anticoagulation

Wed, 24 Apr 2024 04:01:07 +0000

Patients with human immunodeficiency virus (HIV) infection have an increased likelihood of venous thromboembolism (VTE) owing to factors such as acquired protein C and S deficiency, antiphospholipid antibody syndrome, and heightened levels of pro-inflammatory cytokines. This case report highlights an exceptionally uncommon occurrence of deep venous thrombosis in an HIV-infected patient receiving a therapeutic dose of enoxaparin. This underscores the need for cautious consideration of the risk of VTE in HIV-infected individuals, even with preventive or therapeutic anticoagulant treatment. Further research is recommended to investigate HIV as a potential risk factor of prophylactic anticoagulation.