Combined Blockade Of PD-1 and TIGIT is not Sufficient to Improve the Function Of CD8+ T-Cells in Chronic Lymphocytic Leukemia.

Background And Objective: Blockade of immune checkpoint receptors in the treatment of cancers has been mentioned in several studies. Here, we investigated the efficacy of combined blockade of two inhibitory receptors, PD-1 and TIGIT, in restoring functional features of CD8+ T-cells in CLL.

Methods: CD8+ T-cells were separated from the peripheral blood of 11 CLL patients and targeted with malignant B-cells isolated from the same patients.

Tim-3 and PD-1 blocking cannot restore the functional properties of natural killer cells in early clinical stages of chronic lymphocytic leukemia: An study.

Background: Programmed death-1 (PD-1) and T-cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) are two major immune checkpoint receptors expressed on immune cells and their expression is related to the exhaustion phenotype. In the present in vitro study, blocking of PD-1 and Tim-3 molecules was performed on isolated natural killer (NK) cells from patients with chronic lymphocytic leukemia (CLL) to restore their functional properties.

Materials And Methods: NK cells fraction was positively isolated from fresh peripheral blood of 18 CLL patients, treated with anti-PD-1 and anti-Tim-3 blocking monoclonal antibodies and co-cultured with K562 target cells to evaluate their apoptosis induction by Annexin V-PI method.

miR-34a mimic or pre-mir-34a, which is the better option for cancer therapy? KatoIII as a model to study miRNA action in human gastric cancer cells.

Background: Aberrantly expressed microRNAs play important roles in gastric tumorigenesis. However, use of miRNAs as a therapeutic option in gastric cancer still remains as a challenging problem.

Methods: We performed transient transfection of miR-34a-5p mimic and stable transfection of pre-mir-34a into KatoIII cells.

Blockade of PD-1 and TIM-3 immune checkpoints fails to restore the function of exhausted CD8 T cells in early clinical stages of chronic lymphocytic leukemia.

Blocking antibodies targeting immune checkpoint molecules achieved invaluable success in tumor therapy and amazing clinical responses in a variety of cancers. Although common treatment protocols have improved overall survival in patients with chronic lymphocytic leukemia (CLL), they continue to relapse and progress. In the present in vitro study, the application of anti-PD-1 and anti-TIM-3 blocking antibodies was studied to restore the function of exhausted CD8 T cells in CLL.

SDF-1α Reduces Human Natural Killer Cell Cytotoxicity against Chronic Myelogenous Leukemia K562 Cells.

Stromal cell-derived factor-1 alpha (SDF-1α) has been shown to be up-regulated in a variety of malignancies. So that, its expression is associated with poor prognosis and invasiveness. Natural killer (NK) cells are important effector cells against virus-infected and transformed cells.

A comparative study on immunophenotypic characterization and osteogenic differentiation of human mesenchymal stromal cells derived from periodontal ligament and gingiva.

Background: Mesenchymal stem cells (MSCs) derived from periodontal ligament (PDL) and gingiva can be used for the development of cell-based regenerative approaches in dentistry and medicine. The purpose of this investigation was to establish a method for isolation of human stem cells from the PDL and gingiva, multilineage differentiation of those cells, and comparison of periodontal ligament mesenchymal stem cells (PDLMSCs) and gingival mesenchymal stem cells (GMSCs).

Methods: PDL and gingival tissues of third molar teeth were digested enzymatically and the proliferative potential of human PDLMSCs and GMSCs was compared by MTT assay.

Cellular apoptosis: An alternative mechanism of action for caspofungin against .

Background And Purpose: Although the mechanism of action for echinocandins is known, the physiological mechanisms by which these antifungal agents cause cell death via the classical apoptotic pathways are not well-defined yet. Regarding this, the present study aimed to evaluate the mechanisms of caspofungin-induced cell death.

Materials And Methods: For the purpose of the study, the minimum inhibitory concentration (MIC) of caspofungin against (ATCC 90030) was determined using the broth microdilution reference method (CLSI M27-A2 and M27-S4).

Cell Density Counts of the Intestinal Intraepithelial Lymphocytes in the Celiac Patients.

Background: Increased number of intestinal intraepithelial lymphocytes (IELs) is a key histological finding in the diagnosis of celiac disease (CD); however, the number of IELs in celiac patients and healthy subjects may vary from one region to another. Additionally, there are some seronegative celiac patients with a borderline histology.

Objective: To determine the number of the CD3+ and CD8+ IELs T-cells in the celiac patients and healthy subjects (controls) in Isfahan.

Expression analysis of PD-1 and Tim-3 immune checkpoint receptors in patients with vitiligo; positive association with disease activity.

The contribution of immune checkpoint receptors in the immunopathogenesis of various autoimmune diseases has been addressed in previous reports. In this study,  the expression profile of T-cell immunoglobulin and mucin-domain containing-3 (Tim-3) and programmed cell death-1 (PD-1) checkpoint molecules was investigated in CD8 T cells of Vitiligo patients. The association of Tim-3 and PD-1 expression with disease activity was also explored.

Elevated Expression of Tim-3 and PD-1 Immune Checkpoint Receptors on T-CD4+ Lymphocytes of Patients with Asthma.

Asthma is a chronic disorder of the airways characterized by reversible airflow obstruction, inflammation and bronchial hyperresponsiveness. Different immune cells and molecules have been attributed to involve in pathogenesis of asthma. In the current case-control study, the expression of T cell Ig and mucin domain-containing molecule-3 (Tim-3) and programmed death-1 (PD-1) was studied on CD4+ T cells of patients with asthma and normal controls.

Analysis of PD-1 and Tim-3 expression on CD4 T cells of patients with rheumatoid arthritis; negative association with DAS28.

Expression of T cell immunoglobulin and mucin-domain containing-3 (Tim-3) and programmed cell death-1 (PD-1) was studied on CD4 T cells of patients with rheumatoid arthritis (RA). Association of Tim-3 and PD-1 expression with disease activity of RA patients was also addressed. A total of 37 RA patients and 31 sex- and age-matched healthy controls were included in this study.

Tim-3 Up-regulation in Patients with Gastric Cancer and Peptic Ulcer Disease.

Background: T-cell immunoglobulin and mucin domain protein-3 (Tim-3), an inhibitory immunoregulatory receptor, has been recently implicated in tumor biology and tumor-associated immune suppression. In the present study, expression of Tim-3 was evaluated in gastric cancer (GC) and peptic ulcer disease (PUD) at both mRNA and protein levels. Methods: A total of 133 gastric tissue biopsies, comprising 43 from GC cases, 48 from PUD and 42 from non-ulcer dyspepsia (NUD) serving as controls were collected.

Frequency and functional characterization of exhausted CD8 T cells in chronic lymphocytic leukemia.

Objectives: The phenotypic and functional properties of Tim-3 /PD-1 /CD8 cells as exhausted T cells were investigated in chronic lymphocytic leukemia (CLL).

Methods: Frequency of CD8 /Tim-3 /PD-1 exhausted cells was determined by flow cytometry. For functional analysis, magnetic beads-isolated CD8 T cells were stimulated with PHA and PMA/ionocymin to assess their proliferative responses and cytokine production by MTT and ELISA, respectively.

Altered microRNA Expression and Immunosuppressive Cytokine Production by Regulatory T Cells of Ulcerative Colitis Patients.

Regulatory T (Treg) cells are essential for maintenance of peripheral tolerance and prevention of autoimmune diseases in part by producing immunosuppressive cytokines. Recently, microRNAs (miRNAs) have also been involved in autoimmune disorders, not least for their crucial role in the regulation of Treg biology and function. We simultaneously investigated the concentration of IL-35, IL-10, TGF-β, and sCD25 in supernatant of cell culture and the expression patterns of several miRNAs in CD4(+)CD25(+) CD127(-/low) FoxP3(+) Tregs of ulcerative colitis (UC) patients.

Uterine Natural Killer Cell and Human Leukocyte Antigen-G1 and Human Leukocyte Antigen-G5 Expression in Vaginal Discharge of Threatened-Abortion Women: A Case-Control Study.

The immunotolerant human leukocyte antigen-G (HLA-G) molecules have a major role in fetal-maternal tolerance during pregnancy. Interaction between these molecules and uterine natural killer (uNK) cells inhibitory receptors prevents NK cell invasion against fetus trophoblast cells. The aim of this study was to evaluate the percentages of uNK cells and HLA-G1 and HLA-G5 isoforms expression in vaginal discharge of threatened-abortion women in comparison with control.