فهرست مطالب hossein asgarian omran

COVID-19 is one of the biggest pathogens that mainly targets the human respiratory system. Among the preventive methods against contracting COVID-19, vaccination has had an important effect in preventing COVID-19 and is an essential component in prevention. Various vaccines were provided to prevent COVID-19, one of these vaccines was Sinopharm, which was used for cancer patients in Iran, so this study aimed to determine the antibody response following the injection of Sinopharm vaccine in cancer patients in Iran in 2021.

This cross-sectional study was conducted in 2021 on 74 patients with various types of cancers in Amol and Sari cities who received two doses of the Sinopharm vaccine. Subjects participated in the study after obtaining informed consent. Cancer patients who were referred to vaccination centers were asked to refer to the reference laboratory 4 to 6 weeks after the second dose if they wished to determine the antibody level. A 5 cc blood sample was taken 4-6 weeks after receiving the second dose of the vaccine, and then the serum was separated from the samples and stored at -20. The level of SARS-CoV-2 Neutralizing antibody, Anti-RBD, and Anti-Spike IgG were provided by Kit Eliza, Pishtaz Tab Company. The sensitivity and specificity of the kits used for neutralizing antibodies are 100% and 99% respectively, for Anti-RBD 98.4% and 97.7%, and Anti-Spike IgG 98.16% and 99.01% respectively. Finally, according to the instructions of the kit, neutralizing antibody values greater than 2.5 Mg/ml and optical absorption greater than 1.1 for RDB antibody and anti-spike antibody values greater than 8 RU/ml were considered positive.

The average age of the subjects was 57.1±11.7 years. In terms of gender distribution, 45 people (60.8%) were women. The neutralizing antibody status was positive in 41 people (55.4%). There was no significant relationship between the presence of neutralizing antibodies and gender (P=0.811) and age (P=0.443). Antibody against RDB antigen was positive in 31 people (41.9%). There was no significant relation between the presence of antibodies against RDB antigen with gender (P=0.091) and age (P=0.336). Antibody against Spike virus antigen was positive in 20 people (27%). A significant relationship was observed between the presence of antibodies against the Spike antigen and gender (P=0.008) and the proportion of women who produced antibodies against the Spike virus antigen was more than men, but there was no significant relationship between the presence of antibodies against the Spike gene and age (P=0.336).

The results of the present study showed that the vaccination of COVID-19 by Sinopharm in immunocompromised patients such as cancer patients can induce an antibody response, although the percentage is not high. Also, no significant relationship was observed between antibody production and age.

Acute lymphoblastic leukemia (ALL) is the most common cancer among children. The prognostic significance of the cluster of differentiation 34 (CD34) markers in children with B-cell acute lymphoblastic leukemia (B-ALL) is not yet fully understood.

This study is a case-control trial based on the clinical data of 40 children with B-ALL who referred to a pediatric oncology center in the city of Sari, Iran. The data were derived from the demographic findings, laboratory test results at diagnosis, immunophenotyping, transfusion of blood products including packed red blood cells and platelet concentrates, and the frequency and duration of hospitalization due to febrile infection.

Of the participants, 42.5% were CD34-negative and 57.5% were CD34-positive. The mean age of the patients at diagnosis was 3.1 ± 3.3 years (Range:0.1-13.3 years). Also, 60.9% of the CD34-positive children and 47.1% of the CD34-negative ones were boys (P = 0.38). According to the calculated Cohen's d, the relationship of CD34 positivity with transfused packed red blood cell and platelet concentrates was mild -0.15 (95% CI -0.78 to 0.47) (P = 0.55) and moderate 0.49 (95% CI -0.15 to 1.12) (P = 0.29), respectively, which was significant in neither case. Moreover, the relationship of CD34 positivity with the hospitalization frequency of -0.51 (95% CI -1.14 to 0.13) (P = 0.22) and the hospitalization duration of -0.52 (95% CI -1.16 to 0.12) (P = 0.27) due to febrile infection was moderate to strong.

The CD34-positive children with B-ALL experienced less blood products transfusion (except packed red blood cells) and febrile infection in terms of both the frequency and duration of hospitalization during chemotherapy. Therefore, CD34 expression in the B-ALL children was associated with better prognosis.

Thymocyte selection-associated high mobility group box protein (TOX) and members of the nuclear receptor 4A (NR4A) are known as transcription factors involved in T cell exhaustion. To evaluate the mRNA expression of TOX and NR4A1-3 in CD8+ T cells in acute leukemia. Blood samples were obtained from 21 ALL and 6 AML patients as well as 20 control subjects. CD8+ T cells were isolated using MACS. Relative gene expression of TOX and NR4A1-3 was then evaluated using qRT-PCR. Comparison of mRNA expression of TOX in CD8+ T cells showed no significant difference among the study groups (p>0.05), while the expression of NR4A1 was significantly lower in AML patients than in the control group (p=0.0006). Also, the expression of NR4A2 and NR4A3 was significantly lower in both ALL (p=0.0049 and p=0.0005, respectively) and AML (p=0.0019 and p=0.0055, respectively) patients. NR4As expressions were found to be lower in CD8+ T cells from patients with AML and ALL compared to controls, whereas the mRNA expression of TOX showed no significant difference. Although TOX and NR4As are associated with CD8+ T cell exhaustion in solid tumors, they might play different roles in acute leukemia, which requires further investigation.

We aimed to design a B and T cell recombinant protein vaccine of Toxoplasma gondii with in silico approach. MIC13 plays an important role in spreading the parasite in the host body. GRA1 causes the persistence of the parasite in the parasitophorous vacuole. SAG1 plays a role in host-cell adhesion and cell invasion.

Amino acid positions 73-272 from MIC13, 71-190 from GRA1, and 101-300 from SAG1 were selected and joined with linker A(EAAAK)A. The structures, antigenicity, allergenicity, physicochemical properties, as well as codon optimization and mRNA structure of this recombinant protein called MGS1, were predicted using bioinformatics servers. The designed structure was synthesized and then cloned in pET28a (+) plasmid and transformed into Escherichia coli BL21.

The number of amino acids in this antigen was 555, and its antigenicity was estimated to be 0.6340. SDS-PAGE and Western blotting confirmed gene expression and successful production of the protein with a molecular weight of 59.56kDa. This protein will be used in our future studies as an anti-Toxoplasma vaccine candidate in animal models

In silico methods are efficient for understanding information about proteins, selecting immunogenic epitopes, and finally producing recombinant proteins, as well as reducing the time and cost of vaccine design.

Placenta-specific 1 (PLAC1) is one of the cancer-testis-placenta antigens that has no expression in normal tissue except placenta trophoblast and testicular germ cells, but is overexpressed in a variety of solid tumors. There is a lack of studies on the expression of PLAC1 in leukemia. We investigated expression of PLAC1 in Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL).

In this study, we investigated expression pattern of PLAC1 gene in peripheral blood and bone marrow mononuclear cells of newly-diagnosed patients with AML (n=31) and ALL (n=31) using quantitative real-time PCR. Normal subjects (n=17) were considered as control. The PLAC1 protein expression in the samples were also detected using western blotting.

Our data demonstrated that PLAC1 transcripts had 2.7 and 2.9 fold-change increase in AML and ALL, respectively, compared to normal samples. PLAC1 transcript expression was totally negative in all studied normal subjects. Level of PLAC1 mRNA expression in ALL statistically increased compared to normal samples (p=0.038). However, relative mRNA expression of PLAC1 in AML was not significant in comparison to normal subjects (p=0.848). Furthermore, relative mRNA expression of PLAC1 in AML subtypes was not statistically significant (p=0.756). PLAC1 gene expression showed no difference in demographical clinical and para-clinical parameters. Western blotting confirmed expression of PLAC1 in the ALL and AML samples.

Considering PLAC1 expression profile in acute leukemia, PLAC1 could be a potential marker in leukemia which needs complementary studies in the future.

 Metabolism reprogramming is a survival mechanism in acute myeloid leukemia (AML) cells in the tumor microenvironment. Therefore, we investigated the effect of signaling pathway inhibitors on the expression of genes rewired in the metabolic pathway of AML cells.

 HL-60 cells were treated with Idelalisib, MK-2206, and Everolimus, which respectively are selective inhibitors of phosphatidylinositol-3-kinase (PI3K), AKT, and the mammalian target of rapamycin (mTOR), either individually or in combination. The relative expressions of glucose transporter 1, hexokinase 2, pyruvate kinase, pyruvate dehydrogenase E1, citrate synthase, isocitrate dehydrogenase 2, and hypoxia inducible factor 1 subunit alpha were determined by real-time PCR.

 The combined treatment of HL-60 cells with Idelalisib, MK-2206, and Everolimus decreased the expression of glucose transporter 1, hexokinase 2, pyruvate kinase M2, pyruvate dehydrogenase E1, citrate synthase, isocitrate dehydrogenase 2, and hypoxia inducible factor 1 subunit alpha.

 A combination of PI3K/AKT/mTOR pathway inhibitors regulates the expression of genes involved in glycolysis, pyruvate dehydrogenase complex (PDH), and the tricarboxylic acid (TCA) cycle and interferes with metabolic reprogramming and immune evasion mechanisms of AML leukemic cells. Combinational therapy approaches to block these pathways might be a promising and novel therapeutic strategy for targeting the metabolic requirements of AML cells.

This study investigated the role of the immune-checkpoint receptor (ICR), CD244, and its adapter molecules, in CD8+ T cells in acute leukemia.

Blood samples were obtained from 21 acute lymphoblastic leukemia (ALL) and 6 acute myeloid leukemia (AML) patients and 20 control subjects. Relative gene expression of CD244, immune receptor tyrosine-based switch motif-associated protein (SA), EWS/FLI1-activated transcript 2 (EAT-2), and LncRNA-GSTT1-AS1 were evaluated using quantitative reverse transcription polymerase chain reaction.

Expression of CD244, SAP, and EAT-2 were significantly lower in CD8+ T cells from ALL patients than those from control subjects. Interestingly, the expression of SAP was much lower than that of CD244, indicating a lower ratio of SAP to CD244. Also, SAP expression was significantly lower in AML patients compared to the control group. Expression of LncRNA-GSTT1-AS1 showed no significant difference in ALL and AML patients compared to control subjects.

The low SAP/CD244 expression ratio in CD8+ T cells in ALL suggests an inhibitory role for CD244 in ALL.

Expression and location of nucleolin are often abnormal in malignancies, which may result in the production of autoantibodies. Despite this, the identification of such autoantibodies may be essential for the early diagnosis and prognosis of cancers. In this investigation, the recombinant nucleolin protein was generated using an Escherichia coli expression system and was used an indirect enzyme-linked immunosorbent assay to detect anti-nucleolin autoantibodies in cancer patients' sera. Lung cancer patients' autoantibodies displayed the highest seroreactivity with the recombinant protein, with area under the curve of 0.948 and sensitivity and specificity of 85% and 96.67%, respectively (accuracy=92%). Anti-nucleolin autoantibodies were linked with lung tumor size (r=0.793), tumor, node, metastasis staging (r=0.643), and proliferation (r=0.744). These autoantibodies distinguished patients with early-stage lung cancer from healthy controls. Since anti-nucleolin autoantibodies are strongly linked to tumor size, clinical staging, and growth, they can be used to measure how well a treatment is working.

Innate Lymphoid Cells (ILCs) promote tissue homeostasis, contribute to the immune defense mechanisms, and play important roles in the initiation of immune responses and chronic inflammation. To understand the roles of innate lymphoid cells in the pathophysiology of colorectal cancer (CRC) in the mouse model. CRC was induced using azoxymethane (AOM) and dextran sulfate sodium (DSS) in Balb/c mice (the chemically induced group=18 mice), or orthotopic injection of CT-26 cell line into the colon of another set of Balb/c mice (the orthotopic group=14mice). Normal saline was injected into 18 mice, as the sham group. After 80 days, the chemically induced group was divided into two subgroups, dysplasia (8 mice) and reparative change (10 mice), based on pathological examinations. The frequencies of ILC1, 2, and 3 were then measured in colon tissues using flow cytometry by four markers including an anti-mouse lineage cocktail (FITC anti-mCD3/FITC anti-mGr-1/FITC anti-mCD11b/ FITC anti-mCD45R (B220)/FITC anti-mTer-119), PE/Cy7 anti-mouse CD45, PE anti-mouse CD117 (c-kit), and APC anti-mouse IL-33 Rα (ST2). The total ILC population was significantly higher in the chemically induced reparative change compared with the sham group. ILC1 percentage in the chemically induced reparative change was significantly higher compared to those in the other three groups (Sham, chemically induced dysplasia and orthotopic dysplasia). The orthotopic dysplasia group showed more ILC3 percentage than the other groups. ILC1 and ILC3 subgroups increased significantly in reparative and dysplastic experimental CRC respectively. Thus ILC1 may have an inhibitory effect on tumor growth whereas ILC3 promotes tumor progression.

Toxoplasma gondii is a neurotropic parasite with lifelong persistence in the host brain. Many researchers suggested toxoplasmosis as a risk factor for the development of Alzheimer's disease (AD); however, the link between them has not been fully elucidated.

The present study was designed to investigate the effects of chronic toxoplasmosis infection with Types I (RH), II (PRU), and III (VEG) strains alone and in combination on cognitive impairments in Alzheimer's rat model.

Seven months after the inoculation of the strains, AD was induced bilaterally in rats by injecting human amyloid beta 1-42 (Aβ1-42) peptide into the brain hippocampus. Behavioral tests, including the elevated plus maze (EPM) and Morris water maze (MWM) were conducted 10 days after the AD induction.

Our findings showed that chronic infection with RH strain increased anxiety-like behavior in the Alzheimer's rats in the EPM. In agreement with EPM findings, rats infected with the RH strain exacerbated spatial learning disorders in the MWM test; however, it did not affect the spatial memory. Conversely, infection with the PRU strain significantly enhanced spatial learning without being able to improve memory impairments in the Alzheimer's rat model. Improvement in spatial learning and memory impairments were also observed in rats infected with PRU and VEG strains in combination.

Taken together, our findings suggest that chronic infection with PRU strain, as well as PRU and VEG strains in combination, can significantly improve cognitive deficits induced by Aβ1-42 in Alzheimer's rats, while RH strain plays a detrimental role in AD pathogenesis.

Coronavirus disease 2019 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, an indirect ELISA method was designed to measure the human IgM and IgG antibodies against SARS-CoV-2.

Protein sequence of nucleocapsid antigen from SARS-CoV-2 was expressed in E. coli BL21 and then was purified by chromatography. The purified protein was confirmed by SDS-PAGE and Western blotting. An indirect ELISA method was designed to measure the specific IgG and IgM antibodies against SARS-CoV-2 using recombinant N protein. The optimized ELISA method was then applied to measure the IgG and IgM antibodies in 61 infected or recovered COVID-19 patients and in 31 healthy controls. Finally, data obtained from the designed ELISA method were compared with those of a commercially approved ELISA kit.

The recombinant nucleocapsid protein was successfully expressed and purified which was confirmed by SDS-PAGE and Western blotting. The amount of optical densities obtained from the designed ELISA method was similar to those of the commercial kit in 61 patients and 31 controls. The sensitivity and specificity of the designed ELISA method for IgG were 100% compared with the commercial ELISA kit, while the sensitivity and specificity for IgM were 96.72 and 96.77, respectively.

Serological tests alone are not suitable for diagnosis; however, their combination with molecular tests increases the accuracy and sensitivity of the COVID-19 diagnosis. These tests are also vauable for epidemiological studies.

Up-regulation of immune checkpoint ligands is considered as one of the most important immune escape mechanisms in acute myeloid leukemia (AML). Herein, we investigate a relationship between the inhibition of PI3K/Akt/mTOR signaling pathways and the regulation of immune checkpoint ligands in AML cells. The HL-60 cell line was treated with idelalisib as PI3K inhibitor, MK-2206 as Akt inhibitor, and everolimus as mTOR inhibitor either in a single or combined format. Cell viability and apoptosis were evaluated using MTT and flow cytometry assays, respectively. The relative expression of PD-L1, galectin-9, and CD155 was determined by real-time PCR. Our findings demonstrated decreased proliferation and increased apoptosis of HL-60 cells after treatment with idelalisib, MK-2206, and everolimus. As expected, the combined treatment showed a more inhibiting effect than the single treatment. Interestingly, our results elucidated that the expression of PD-L1 and Gal-9 but not MK-2206 decreased after treatment with idelalisib and everolimus. Regarding CD155, the expression of this molecule was downregulated after treatment with everolimus, but not idelalisib and MK-2206. However, combined treatment of HL-60 cells with two or three inhibitors decreased the expression levels of PD-L1, Gal-9, and CD155 checkpoint ligands. We showed that PI3K/Akt/mTOR pathway inhibitors not only serve as cytotoxic drugs but also regulate the expression of immune checkpoint ligands and interfere with the immune evasion mechanisms of AML leukemic cells. Combinational treatment approaches to block these pathways might be a promising and novel therapeutic strategy for AML patients via interfering in immune escape mechanisms.

Recurrent implantation failure is one of the problems associated with in vitro fertilization cycles. The aim of this study was to evaluate the results of pregnancy using intralipid infusion in infertile women with history of two implantation failures.

A clinical trial was conducted in 80 infertile women in the infertility center in Sari Imam Khomeini Hospital, Iran 2020. In all samples, the level of peripheral blood natural killer (NK) cells was measured two weeks before the intervention using flow cytometry. The participants were divided into an intervention group (n=40) and a control group (n=40) by SAS statistical software. Two days before embryo transfer, patients in intervention group underwent intra lipid infusion (2 ml of 20% solution in 250 ml sterile saline) for two hours and the control group received normal saline (250 ml) infusion. Clinical pregnancy (detection of fetal heart rate by ultrasound) rate was compared between the two groups. Data were analyzed using Chi-square, Mann-whitney, and t-test.

Clinical pregnancy rate was higher in intervention group after intralipid infusion (30%) compared with the control group (10%) (P=0.025). There were no significant differences between the two groups in the level of NK cells and peripheral blood lymphocytes (P<0.05).

Intralipid infusion improved clinical pregnancy rate in women with history of recurrent implantation failure. However, further studies are required on the possible mechanism of immunological effects of interlaipid in NK cells.

Tumor-targeted therapy with small-molecule inhibitors (SMIs) has been demonstrated to be a highly effective therapeutic strategy for various cancers. However, their possible associations with immune evasion mechanisms remain unknown. This study examined the association of inhibitors of the protein kinase B (AKT), mammalian target of rapamycin (mTOR), and Bruton’s tyrosine kinase (BTK) signaling pathways with the expression of immune checkpoint ligands programmed death-ligand 1 (PD-L1), CD155, and galectin-9 (Gal-9) in a breast cancer cell line. MCF-7 cells were treated with everolimus, MK-2206, and ibrutinib. AnMTT assay was used to determine the optimal dose for all drugs. A real-time polymerase chain reaction was utilized to measure the mRNA expression of PD-L1, CD155, and Gal-9. The western blot technique was also employed to evaluate the protein expression of the phosphorylated signal transducer and activator of transcription 3 (STAT3). The optimal doses of everolimus, MK-2206, and ibrutinib were observed to be 200, 320, and 2000 nM, respectively. The PD-L1 and CD155 mRNA expression was significantly decreased following the treatment with everolimus and ibrutinib, but not with MK-2206. There were no differences in Gal-9 expression between the single-treated and control groups; however, combined treatment with everolimus and ibrutinib increased its mRNA expression. Everolimus and ibrutinib both inhibited constitutive STAT3 phosphorylation in MCF-7, which was more pronounced in combination treatment. The findings regarding the modulation of PD-L1, CD155, and Gal-9 molecules by SMIs emphasize the crosstalk between the expression of these immune checkpoint molecules and AKT/mTOR/BTK signaling pathways through STAT3 as a critical transcription factor.

Tumor-targeted therapy with small-molecule inhibitors (SMIs) has been demonstrated to be a highly effective therapeutic strategy for various cancers. However, their possible associations with immune evasion mechanisms remain unknown. This study examined the association of inhibitors of the protein kinase B (AKT), mammalian target of rapamycin (mTOR), and Bruton’s tyrosine kinase (BTK) signaling pathways with the expression of immune checkpoint ligands programmed death-ligand 1 (PD-L1), CD155, and galectin-9 (Gal-9) in a breast cancer cell line. MCF-7 cells were treated with everolimus, MK-2206, and ibrutinib. AnMTT assay was used to determine the optimal dose for all drugs. A real-time polymerase chain reaction was utilized to measure the mRNA expression of PD-L1, CD155, and Gal-9. The western blot technique was also employed to evaluate the protein expression of the phosphorylated signal transducer and activator of transcription 3 (STAT3). The optimal doses of everolimus, MK-2206, and ibrutinib were observed to be 200, 320, and 2000 nM, respectively. The PD-L1 and CD155 mRNA expression was significantly decreased following the treatment with everolimus and ibrutinib, but not with MK-2206. There were no differences in Gal-9 expression between the single-treated and control groups; however, combined treatment with everolimus and ibrutinib increased its mRNA expression. Everolimus and ibrutinib both inhibited constitutive STAT3 phosphorylation in MCF-7, which was more pronounced in combination treatment. The findings regarding the modulation of PD-L1, CD155, and Gal-9 molecules by SMIs emphasize the crosstalk between the expression of these immune checkpoint molecules and AKT/mTOR/BTK signaling pathways through STAT3 as a critical transcription factor.

Several PI3K/Akt/mTOR pathway inhibitors and TLR agonists induce tumor cell death. However, the mechanisms of these therapeutic approaches in acute myeloid leukemia (AML) cells are still unknown. To investigate the effects of BEZ235, as a dual inhibitor of PI3K and mTOR pathways, and TLR7/8 agonist R848 on the expression and regulation of the immune inhibitory molecules in myeloid leukemia cells. WEHI-3 leukemia cells were incubated with dual PI3K and mTOR inhibitor BEZ235 and TLR7/8 agonist R848 for 48 hrs. Firstly, cell viability was assessed by MTT method. The semi-quantitative relative mRNA expression of Galectin-9 (Gal-9), PD-L1, PVR, and STAT3 was assessed according to HPRT as a housekeeping gene. Finally, the protein expression of phosphorylated STAT3 was evaluated by western blotting analysis. WEHI-3 cells showed growth inhibition following treatment with BEZ235 and R848 whose combination exerted more proliferation arrest. The mRNA expression of Gal-9, PD-L1 and PVR immune checkpoint molecules significantly reduced in treated cells with BEZ235 and R848. Combined treatment indicated more reduction compared with the single treatment. Finally, the expression and phosphorylation of STAT3 were down-regulated after a single or dual treatment with BEZ235 and R848. Our results conclude that treatment with the combination of BEZ235 and R848 interferes with immune evasion mechanisms through STAT3-signaling pathway in WEHI-3 leukemia cells.

Frizzled-7, the most common receptor of the Wnt signaling pathway, was significantly over-expressed in gastric (GC) and colorectal (CRC) cancers and stimulated tumorigenesis. The extracellular domain of Fzd7 (sFzd7) as a decoy receptor, could competitively bound with ligands and antagonize the interaction between Fzd7 receptors and Wnt ligands. 

We expressed and purified the extracellular region of Fzd7 including cysteine-rich domain (33 aa–185 aa) from Escherichia coli by chromatography. The effect of sFzd7 was evaluated on AGS gastric and SW480 colon cancer cell lines expressing high levels of Fzd7 receptor. Accordingly, cell viability and apoptosis were measured using MTT and flow cytometry assays, respectively. Real-Time PCR determined the relative expression of the β-catenin and cyclin-D1 genes. 

After three days of treatment with sFzd7, the viability of AGS and SW480 cell lines was decreased in a dose-dependent manner. In addition, sFzd7 at concentrations of 10 and 20 ug/ml increased the rate of apoptosis. Especially at the concentration of 20 ug/ml, the apoptosis rate was remarkably high in AGS (P-value= 0.003) and SW480 cells (P-value= 0.0007). Finally, the expressions of β-catenin (P-value= 0.01) and cyclin-D1 (P-value= 0.02) were obviously decreased in SW480 cells. The same results were obtained in AGS cells, although not statistically significant. 

sFzd7 decoy receptor inhibits tumor cell progression by attenuating the Wnt pathway through inhibiting Fzd7 receptors and Wnt ligand interaction. Hence, sFzd7 can be proposed as a candidate therapy for GC and CRC cells with high levels of Fzd7 expression.

The role of immune checkpoint receptors in T-cell exhaustion has been demonstrated in several cancers. We investigated the co-expression of TIGIT/PD-1 and LAG-3/PD-1 cells in patients with chronic lymphocytic leukemia (CLL). The frequencies of TIGIT+PD-1+CD8+and LAG-3+PD-1+CD8+cells and relative mRNA expression of LSECtin and CD155 were examined in PBMCs from 33 CLL patients and 20controls. The percentage of TIGIT+PD-1+CD8+cells was significantly higher in CLL patients than in control subjects, with the preference in advanced-stage patients. However, LAG-3+PD-1+CD8+cell percentage was significantly lower in CLL patients than in the control subjects, and no significant differences were found between the early and advanced stages of the disease. An increase in the mRNA expression level of LSECtin, but not that of CD155, was observed in CLL patients compared to the control subjects. Collectively, a higher co-expression of PD-1 and TIGIT on CD8+ T-cells in CLL compared to control subjects suggests an important role of TIGIT in T-cell exhaustion in CLL patients especially those with advanced disease.

Placenta-specific protein 1 (PLAC1) is one of the members of cancer-testis antigens family that has limited expression in normal tissue, but is upregulated in a variety of malignant tissues. Considering the lack of studies on the expression of FCRL1 in CML and CLL, the current study was conducted to examine the expression pattern of PLAC1 gene in these leukemias.

Fresh peripheral blood samples were collected from 6 CML and 10 CLL patients. In addition, peripheral blood samples of 10 healthy individuals were collected in EDTA as control group. All patients and healthy individuals signed a consent letter before sampling. The mononuclear cells were separated using ficoll-hypaque gradient centrifugation. Isolated mononuclear cells were used for RNA extraction and cDNA synthesis using RT-PCR method. Then, PLAC1 transcript expression in comparison to GAPDH were detected via Real-Time PCR. The statistical analyses were performed using chi-square test in SPSS.

All 10 normal samples were negative for PLAC1. The PLAC1 expression was found to be statistically different in CML group (4 out of 6 cases) compared with that in the normal group (P value = 0.000). However, CLL revealed no significant difference compared to normal individuals for PLAC1 expression (P Value = 0.648). In a significant percentage of CML patients, PLAC1 expression was positive but in CLL patients PLAC1, transcript expression was not evident.

It seems that PLAC1 could potentially be proposed as a biomarker in CML to aid in the diagnosis, prognosis, and treatment in the future.

Hashimoto’s thyroiditis (HT) is themost prevalent autoimmune disease, and there is no definitive treatment available for this disease. To find the appropriate therapeutic approach, it is necessary to determine the mechanism of this disease. To achieve this purpose, the frequency of CD4+ T cells was evaluated in patients with HT and compared with healthy individuals.

Twenty-six female patients with HT, aged 20 - 45 years, enrolled in this study. Based on the level of thyroglobulin antibody (anti-TG) and anti-thyroid peroxidase antibody (anti-TPO) in serum of patients with HT, they were divided into two groups. The serum level of anti-TPO was above 100 IU/mL in the group 1 (n = 13), whereas the serum levels of both anti-TPO and anti-TG were above 100 IU/mL in the group 2 (n = 13). Eleven healthy women were considered control group, or group 3. Using flow cytometry, the frequency of T helper (Th)1, Th2, Th17, T regulatory type 1 (Tr1), and LT CD4+ IL-4+ IL-17+ cells and mean fluorescent intensity (MFI) of their related cytokines were evaluated.

The frequency of Th2 cells in the groups 1 (anti-TPO > 100) and 2 (anti-TPO > 100 and anti-TG > 100) were more than control group. Only the difference between groups 3 (healthy control) and 2 was significant (P = 0.022). The frequency of LT CD4+ IL-4+ IL-17+ cells in the group 1 was significantlymore than group 3 (P = 0.027); However, the difference between group 2 and 3 was not significant (P = 0.126). The expression of interferon-gamma (IFN-γ) in the group 2 (P = 0.001) and group 1 (P = 0.001) was significantly higher than group 3. The frequency of Th17, Th1, and Tr1 cells and MFI of IL-17 and IL-10 were not significantly different between the study groups.

In the present study, no significant differences were observed in the frequency of Th17 and Tr1 cells and in MFI of IL-17 and IL-10 in comparison to healthy individuals. Therefore, trying to make a change in the population of these cells probably does not have a significant therapeutic effect. Since Th2 cells and the expression of IFN-γ increased in women with HT, reducing the frequency of Th2 cells or the expression of IFN-γ may be effective in controlling the disease progression. It may be helpful for these patients to prevent the progression of the disease.

SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is recognized for the first time in Wuhan, China. The cytokine storm is a known factor causing major clinical symptoms leading to death in COVID-19 patients.

To investigate and compare the serum levels of different cytokines in COVID-19 patients with different clinical severity.

Concentrations of serum cytokines, including IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, IFN-γ, and GM-CSF, were measured in 61 COVID-19 patients and 31 normal controls with ELISA. We investigated the correlation between the levels of these cytokines and clinical severity, CRP level, neutrophil and lymphocyte count in patients with COVID-19.

Our data indicated that the levels of IL-1β, IL-2, IL-4, IL-6, IL-8, TNF-α, IFN-γ, and GM-CSF, but not IL-10 were significantly increased in COVID-19 patients compared to normal controls. Statistical analysis showed that the level of IL-1β, IL-2, IL-4, IL-6, IL-8, TNF-α, IFN-γ, and GM-CSF were higher in severe COVID-19 than those of mild cases. The concentrations of all mentioned cytokines were negatively associated with the absolute count of lymphocytes, and positively correlated with the CRP level and the absolute count of neutrophils.

The current study suggests that high levels of various cytokines correlate with the disease severity and immunopathogenesis of COVID-19.

Tumour cells may be resistant to radiotherapy that results in unsuccessful cancer treatment in patients. The aim of this study was to evaluate the sensitizing effect of atorvastatin (ATV) on breast cancer (MDA-MB-231) and non-small cell lung cancer (A-549) cells following exposure to ionizing radiation (IR). These cells were treated with ATV and exposed to X-ray at dose 4 Gy. The radiosensitizing effects of ATV were evaluated by flow cytometry and anti-proliferation assays. The production of reactive oxygen species (ROS) was determined in irradiated and treated cells with ATV. The findings of this study showed that ATV increased the percentage of apoptotic cells in irradiated breast and lung cancer cells. ATV exhibited anti-proliferative effect on cancer cells and increased cell death induced by IR. ATV increased ROS production in irradiated cells. The present study demonstrates that ATV has radiosensitizing effect on breast and lung cancer cells through increasing apoptosis, ROS production and cell death induced by IR.

Parkinson disease (PD) is the second most common neurodegenerative disease affecting older individuals with signs of motor disability and cognitive impairment. Epicatechin (EC) and edaravone have neuroprotective effects most probably due to their antioxidant activity; however, a limited number of studies have considered their role in PD. This research aimed at investigating the neuroprotective effect of EC and edaravone in a neurotoxin-induced model of PD.

An in vitro model of PD was made by subjecting SH-SY5Y neuroblastoma cells to neurotoxin: 6-hydroxydopamine (6-OHDA) 100 µM/well. The cytoprotective effect of EC and edaravone in five concentrations on cell viability was tested using the MTT assay. The apoptotic assay was done by annexin V and propidium iodide method using flow cytometry.

According to the MTT assay analysis, EC and edaravone had protective effects against 6-OH DA-induced cytotoxicity in SH-SY5Y neuroblastoma cells that were much more significant for edaravone and also a relative synergistic effect between EC and edaravone was observed. The apoptotic analysis showed that edaravone alone could decrease early and late apoptosis, whereas EC diminished early apoptosis, but enhanced late apoptosis and necrosis. Besides, co-treatment of edaravone and EC had a synergistic effect on decreasing apoptosis and increasing cell viability. 

The protective effect of edaravone on apoptosis and cytotoxicity was demonstrated clearly and EC had a synergistic effect with edaravone.

The Th17, Th1 and dual Th17/Th1 cells are important players in rheumatoid arthritis (RA) disease. To assess their roles, the frequency and impact of these cells were investigated in patients with different disease activity. In 14 new cases and 41 established RA patients in comparison with 22 healthy controls, the percentages of Th17, Th1 and dual Th17/Th1 cells were determined by flow-cytometry and their correlations were investigated with disease activity score (DAS28). Moreover, serum levels of IL-6 and IL-17 as inducer and functional cytokines for Th17 were investigated. Finally, serum levels of anti citrullinated protein antibody (ACPA) and rheumatoid factor (RF) were assessed. Percentage of Th17 cells in RA patients were increased in comparison with healthy controls (p

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the western world. This health problem is caused due to the accumulation of mature B-lymphocytes in the peripheral blood and bone marrow. In the course of cancer, CD4+ T cells become “exhausted” and characterized with poor effector functions and the expression of multiple inhibitory receptors. To investigate the frequency and functional properties of exhausted CD4+ T lymphocytes in patients with CLL. Peripheral blood mononuclear cells were obtained from 25 untreated CLL patients and 15 healthy volunteers. CLL patients were clinically classified according to the Rai staging system. The frequency of CD4+/Tim-3+/PD-1+ cells was obtained by flow cytometry. To evaluate cell proliferation and cytokine production, CD4+ T cells were isolated and stimulated with phytohemagglutinin and PMA/ionomycin. Concentrations of IL-2, IFN-γ, TNF-α, and IL-10 were measured in the culture supernatants of stimulated cells by the ELISA technique. The percentage of CD4+/Tim-3+/PD-1+ cells was significantly higher in CLL patients than that of healthy controls. CD4+ T cells from CLL patients showed lower proliferative responses, a lower production of IL-2, IFN-γ, and TNF-α, and a higher production of IL-10, compared to healthy controls. CD4+ T cells from CLL patients in advanced clinical stages showed more exhaustion features than those of early stages. Given that the exhaustion phase of T cells can be reversible, targeted blocking of immune inhibitory molecules could be a promising tool to restore the host immune responses against leukemic cells in CLL.