zahra faghih

The role of memory T cells in orchestrating memory responses to previously known tumor antigens is well documented. The aim of this study was to assess the frequency of different memory T cell subsets in tumor-draining lymph nodes of patients with bladder cancer (BC) and their prognostic significance. Mononuclear cells were isolated from 50 tumor-draining lymph nodes of untreated patients with BC and stained with antibodies against the markers CD8, CD95, CD45RO and CCR7. Data were collected using the FACSCalibur flow cytometer and analyzed using FlowJo software. Among the CD8+ cytotoxic lymphocytes, the frequency of different subsets was determined including total memory cells (CD8+CD45RO+CD95+), T central memory (TCM: CD8+CCR7+CD45RO+CD95+), T effector memory (TEM: CD8+CCR7−CD45RO+CD95+), T stem cell memory (TSCM: CD8+CCR7+CD45RO−CD95+) and naïve T cells (CD8+CCR7+CD45RO−CD95−). The analysis revealed that on average 49.32±20.15 (between 1.62% and 87.20%) percent of CD8+ lymphocytes in draining lymph nodes of BC had a memory phenotype. TCM cells showed the highest frequency (34.71±17.04), while TSCM cells (7.51±8.53) demonstrated the lowest. The total frequency of memory cells tended to be higher in patients with tumor invasion to muscle layer (P=0.052) and stage III (P=0.042) than in patients without invasion and stage I. The TCM subset was more frequent in patients with necrotic tumors than in patients without necrosis (P=0.048). TSCM significantly increased in patients with N2 compared to N0 (P=0.042). Conversely, the ratio of TSCM cells to total memory cells was higher in lower tumor stages (P=0.059), tumors without muscle invasion (P=0.026) and low T grouping (P=0.043). Overall the data indicated an increase in the frequency of memory T cells and their TSCM and TCM cells with tumor progression. In contrast, the ratio of TSCM to total memory cells was higher in less advanced tumors. These results suggest that the immune system is frequently exposed to tumor antigens and strives to create a memory T cell reservoir, but this is suppressed by inhibitory factors provided by the tumor. These findings emphasize the importance of understanding the dynamic interplay between memory T cell subsets and BC progression.

Natural killer (NK) cells are crucial innate components in anti-tumor immunity. However, the clinical impacts and their phenotypes in bladder cancer (BC) remain unclear. To assess the clinical significance of NK cell subsets in tumor-draining lymph nodes of patients with BC. In a cross-sectional study, pelvic lymph nodes were obtained from 49 untreated patients with BC. Mononuclear cells were isolated and immunophenotyped using CD3, CD56, CD16, CD27, and CD11b markers. NK cells were then classified based on their expression patterns of CD56/CD16 (conventional) and CD27/CD11b (new). On average, NK cells constituted 2.99±1.44% of the total lymphocytes in the draining lymph node of patients with BC. The CD56dim and regulatory NK subsets (CD27+CD11b+/-) were the predominant old and new NK, respectively. The NK cells significantly increased in patients with at least one involved node (LN+) compared with those with free nodes (LN-; p=0.022). Conversely, CD56dimCD16- subset significantly decreased in higher stages (p=0.032) and in tumors with muscle invasion (p=0.038). Significant variations were also observed in different T-stages (p<0.05). Regarding new classification, the frequency of CD11b+ regulatory NK cells was significantly lower in node-positive patients (p=0.025). These findings emphasize the dynamic nature of NK cell subsets in bladder cancer and their potential relevance in disease progression and management, suggesting potential implications for therapeutic strategies targeting these specific subsets.

Activatory or inhibitory immune checkpoints regulate the activity of the immune system. Programmed cell death receptor 1 (PD-1 is an inhibitory immune checkpoint that their overexpression reflects the exhaustion of the immune system. However, it is still unclear how it affects the prognosis of colorectal cancer (CRC). This study aimed to investigate the prognostic value of PD-1 in patients with CRC according to tumor location.

In a cross-sectional study during 2020-2021, a number of 136 patients with history of CRC who underwent surgery at Al-Zahra Hospital in Isfahan between 2013 and 2017 were selected and evaluated retrospectively. Immuno-histochemical staining of tissue samples was performed for PD-1 marker and the expression of this marker was determined in the center and invasive margins of the tumor. Data on survival and date of death of patients were completed through the patient file and confirmed through the civil registry.

High expression of PD-1 in invasive margin was significantly related to lower T stage (T1/2) in left tumors, low M stage (M0) in right tumors, absence of metastasis in right and left tumors, larger tumor size (≥ 5 cm) in right-sided tumors. The expression of this marker in any tumor areas was not significantly related to the survival of the patients.

The findings of this study showed that high expression of PD-1 is related to the lower stages of the CRC, but it is not a good indicator for the prognosis of patients with colon cancer.

The p53 mutation is uncommon in Epstein–Barr virus-linked gastric carcinoma, but its suppression occurs through mechanisms such as ubiquitin specific peptidase 7 (USP7) inhibitions via Epstein–Barr virus nuclear antigen-1 (EBNA1) activity. This study aimed to evaluate the effect of EBNA1 on p53-inhibiting gene expression and the impact of USP7 inhibition on p53 suppression.

MKN-45 cells were transfected with the EBNA1 plasmid. A stable EBNA1 expression cell line was developed through selection based on hygromycin B resistance. Murine double minute (MDM)4, MDM2, sirtuin (SIRT)3, histone deacetylase (HDAC)1, proteasome 26S subunit, Non-ATPase (PSMD)10, USP7, and p53 expression were checked using real-time PCR. Also, cells containing EBNA1 or control plasmid were treated with GNE-6776, and the expression of the interested genes and cell survival were assessed.

MDM4, MDM2, and PSMD10 were significantly upregulated in the MKN-45 cell line following EBNA1 transfection. Morphological changes were observed in the cells harboring EBNA1 after 20 days. In the control cells, USP7 inhibition significantly upregulated the HDAC1, PSMD10, MDM4, and MDM2 genes after 24 h, but downregulated these genes after four days. In the EBNA1-harboring cells, MDM2, MDM4, and PSMD10 genes were significantly upregulated after 24 h, and this effect was sustained for all genes except for MDM4, even after four days. Furthermore, USP7 inhibition induced apoptosis in both cell groups.

EBNA1 enhances the expression of p53-inhibiting genes. Two events—p53 protein overexpression and apoptosis activation—followed the suppression of the USP7 protein and provided evidence for its possible function. The significance of the EBNA1-USP7 interaction in p53 suppression warrants additional investigation and possibly reconsideration.

Let G be a compact Lie group. This article shows that a contraction pseudo-differential operator Aτ on Lp(G) has a Dominated Ergodic Estimate (DEE), and is trigonometrically well-bounded. Then we express ergodic generalization of the Vector-Valued M. Riesz theorem for invertible contraction pseudo-differential operator Aτ on Lp(G). For this purpose, we show that Aτ is a Lamperti operator. Then we find a formula for its symbols τ. According to this formula, a representation for the symbol of adjoint and products is given.

Paspalum is one the largest genera of Poaceae in tropical and subtropical habitats from sandy coastal zone to salt marshes. In Iran, there is only two species mainly distributed in southern coasts of the Caspian Sea. These are cold and flood resistant plants and are cultivated as turf grass. The flooding and drought caused some anatomical modifications in this genus. In this project, for the first time in Iran, Paspalum is studied morphologically, micro-morphologically and anatomically. Studies were done on 11 natural accessions by use of qualitative and quantitative features. Multivariate statistical analyses including principle component analysis (PCA) and cluster analysis by WARD method were done. Leaf, lemma and palea studies by scanning electron microscope showed salt galnds on dorsal epidermis. Results of this study showed that selected morphological and anatomical features are capable of species separation.

NK (natural killer) and NKT (natural killer T) cells, as components of innate immune system, play a crucial role in tumor progression and dissemination. To investigate the percentages of NK cells, NKT cells, iNKT (invariant natural killer T) cells, total T lymphocytes as well as activated T lymphocytes, in tumor draining lymph nodes (TDLNs) of patients with breast cancer (BC) and their association with different clinic-pathological features of the patients. Axillary lymph nodes were obtained from 30 Iranian women with breast cancer. After routine pathological evaluations, mononuclear cells were separated from their lymph nodes and incubated with appropriate fluorochrome conjugated monoclonal antibodies specific for CD3, HLA-DR, CD16/56, and Vα24Jα18-TCR. Data were collected on a four-color flow cytometer and analyzed by CellQuest software. The mean percentages of NK (CD3-CD16/56+), NKT (CD3+CD16/56+) and iNKT (Vα24Jα18-TCR+) cells in TDLNs mononuclear cells of BC patients were 2.04%, 2.44% and 0.1%, respectively. A significant decrease in the percentages of NK and iNKT subsets in patients with grade I was observed compared to grade III (p=0.03 and p=0.01, respectively). Moreover, NK cells were increased in patients with grade III of BC compared to grade II (p= 0.003). The increase in the percentage of NK and iNKT cells in TDLNs of patients with higher grade of BC might suggest a suppressive phenotype for these cells in breast cancer, which merit more functional investigation.

Colony stimulating factors (CSFs) are a group of diverse glycoproteins which induce and regulate proliferation and differentiation of hematogenic progenitors in the bone marrow. However, increasing evidence also shows that these factors can also affect and provoke proliferation of non-hematopoietic cells including tumor cells. Therefore, we assessed Granulocyte (G-CSF), Monocyte (M-CSF) and Granulocyte-Monocyte (GM-CSF) colony stimulating factors the serum of breast cancer (BC) and their association with pathological and paraclinical factors of the disease. Sixty-two untreated patients with BC as well as 54 age-sex matched controls without any history of cancer and autoimmunity in themselves and their first degree relatives were enrolled. After assigning a consent form, 5 milliliters of peripheral blood were obtained and their serums were separated. The levels of growth factors were then checked by cytokine bead array methods. The data were analyzed by SPSS18 and P-values less than 0.05 were considered as significant. The mean expression of G-CSF, M-CSF and GM-CSF was measured to be 14.18 ± 13.61, 6.11 ± 5.62 and 63.48 ±83.22 in the serum of BC patients, respectively. However, there was no significant difference between patients and controls (P>0.05), further analysis revealed that with increase in the stage of disease from I to III, the serum level of GM-CSF significantly elevated (P=0.016). The results collectively suggest an anti-tumorigenic role for GM-CSF in breast cancer, however, it needs to be confirmed in a more comprehensive studies with more sample size.

Recently use of antifungal drugs in human medicine has been increased, especially with the advent of AIDS epidemic. Despite the growing list of azoles, their clinical value has been limited by their relatively high risk of toxicity and the emergence of drug resistance. Efforts have focused on the development of new, less toxic and more efficacious antifungal agents. We previously described synthesis of some new azole derivatives. We also evaluated all the synthesized compounds for their antifungal activity.  Most of our compounds showed desirable activity against different species of microorganisms. Here we choose thirteen of these compounds, 5 bentriazole derivatives (1a-5a), 5 imidazole derivatives (1b-5b) and 3 triazole derivatives (1c-3c) to evaluate their cytotoxic activities against a human cancer cell line (MCF-7) using colorimetric MTT cytotoxic assay. Their cytotoxic activities were compared to clotrimazole as a positive control. Our results collectively showed that most of our synthesized compounds had less cytotoxicity against MCF-7 compared to clotrimazole.

Traditional approaches in Continuing Medical Education (CME) appear to be ineffective in any improvement of the patients’ care, reducing the medical errors, and/or altering physician's behaviors. However, they are still executed by the CME providers, and are popular among the majority of the physicians. In the present study, we have done our best to explore the parameters involved in the degree of CME programs’ effectiveness in Iran.
In this study, 31 participants, consisting of general practitionares, CME experts and providers, were recruited to participate in in-depth interviews and field observations concerning experiences with CME. Application was made of the qualitative paradigm along with the qualitative content analysis, using grounded theory data analysis methodology (constant comparative analysis).
Our analysis demonstrated that: based on participant experiences, the insufficient consistency of the training program contents with the demands of GPs, besides non-beneficiary programs for physicians in addition to non-comprehensive educational designs, created a negative attitude to the continuing education among physicians. This could be defined by unrealistic continuing education, which is the main theme here.
Impracticable continuing education has created a negative attitude toward the CME programs among physicians so much so that they consider these programs less important, resulting in attending the said programs without any specific aim: they dodge absenteeism just to get the credit points. Evidently, promoting CME programs to improve the performance of physicians requires factual needs assessment over and above adaptation of the contents to the physicians’ performance.

Cytotoxic CD8 T cells, as essential parts of the adaptive immune system, play pivotal roles in anti-tumor immune responses. It is well documented that cytokine expression profiles and activation status of these cells during anti-tumor immune responses affect the outcome of host-tumor interaction.
To investigate the percentages of CD8 lymphocytes and their subsets in tumor draining lymph nodes of patients with bladder cancer.
Forty-five patients with bladder cancer, candidate for radical cystectomy, were recruited. Mononuclear cells were isolated from draining lymph nodes using Ficoll-Hypaque gradient centrifugation, and were activated by PMA/Ionomycin in the presence of Golgi inhibitors. The cells were then permeabilized and stained with appropriate flourochrome conjugated antibodies against CD3, CD8, IFN-γ, IL-17 and IL-4 molecules. Data were collected on a four-color flow cytometer and analyzed by CellQuestPro software.
Despite no difference in the frequency of IL-17 producing CD8 (Tc17) lymphocytes, the mean expression of IL-17 in this subset was significantly elevated in high-grade patients (p=0.011). The percentage of double positive IFN-γ/IL-17 CD8 lymphocytes was also significantly increased in node positive patients compared to node negative ones (p=0.046). Our results also demonstrated that the percentage of IFN-γ producing CD8 (Tc1) lymphocytes was significantly increased in the patients with higher histological grade compared to those with lower ones (p=0.038).
IFN-γ and IL-17 producing CD8 T cells may increase in advanced stages of bladder cancer, but their correlation with tumor prognosis remains to be investigated.

Colon microbiota, as a complex and diverse population, has been shown to be either pro- or anti-tumorigenic, depending on its content. The composition of microbiota critically determines the differentiation, activation, and expansion of T cells by which pro- or anti-tumorigenic effects of microbes are frequently reported to be mediated. In this review study, we specified an imbalance in microbiota and T cells in particular regulatory T cells and Th17 cells in colon cancer. We also aimed to discuss evidence, suggesting the contribution of microbiota to carcinogenesis or anti-carcinogenesis through influencing T cells..

Continuing Medical Education (CME) has been considered as a lifelong commitment for doctors to provide the optimal care for patients. Despite a long history of creating CME programs, outcomes are far from ideal. The present qualitative study aims to clarify the barriers affecting effectiveness of the CME programs in Iran based on the experiences of general practitioners.
Sixteen general practitioners were recruited to participate in in-depth interviews and field observations concerning experiences with CME. The study was performed using a qualitative content analysis method. The codes, categories and themes were explored through an inductive process in which the researchers moved from specific to general.
The participants’ experiences identified a number of barriers, particularly insufficient interaction with the instructors; additional problems included the teachers’ use of an undifferentiated approach; unreal and abstract CME; and ignorance of the diverse reasons to participate in CME.
Based on the study results, there are multiple barriers to effective implementation of CME in Iran. The key barriers include insufficient interaction between the trainees and providers, which must be considered by other stakeholders and program designers. Such interactions would facilitate improved program design, invite more specific tailoring of the education to the participants, allow for more effective educational methods and set the stage for outcome evaluation from the learners actually applying their new knowledge in practice. Replication of these findings with another sample would improve confidence in these recommendations, but these findings are broadly consistent with findings in the educational literature on improving the efficacy of CME.

CD8+ cytotoxic T lymphocytes have been recently divided based on their cytokine expression profile. To evaluate the percentages of CD8+ lymphocytes and their effector subsets including Tc1, Tc2 and Tc17 in the tumor draining lymph nodes (TDLNs) of patients with breast cancer. Single cell suspensions were obtained from TDLNs of 42 patients with breast cancer. Staining of the cell surface markers and intracellular cytokines was performed using appropriate fluorochrome-conjugated antibodies. The data was acquired on a four-color flow cytometer and was analyzed by CellQuestPro software package. The percentages of different CD8+ cell subtypes (Tc1, Tc2 and Tc17) were quantified in CD8+ T lymphocytes. The comparison was made between LN+ versus LN- patients, as well as patients in different clinico-pathological status. The percentage of Tc1, Tc2 and Tc17 subsets were not significantly different between LN+ and LN- patients. Despite no difference in the percentages of Tc1 cells in LN+ patients with infiltrative ductal carcinoma (IDC), the mean expression of IFN-γ by Tc1 cells decreased significantly in comparison to LN- patients. On the other hand, the percentages of Tc2 and Tc17 effector subsets were increased in advanced stages (p=0.018 and p=0.009, respectively). As the first study to investigate various effector subtypes of CD8+ lymphocytes in TDLNs of patients with breast cancer, our data collectively suggests a positive association between IL-17- and IL-4-producing CD8+ T cell percentages (Tc2 and Tc17) in TDLNs with breast cancer progression. Although the number of Tc1 cells seems not to be affected by cancer progression, down-regulation of IFN-γ by these cells seems to be associated with tumor metastasis to TDLNs. These findings may have implications in cancer immunotherapy based on CD8+ effector subsets.

Osteoarthritis (OA) is the most common form of arthritis seen clinically. Current treatments for OA are limited to decreasing associated pain, maintaining or improving joint function, and minimizing disability. However, these treatments have no effect on the regeneration of hyaline cartilage. Since mesenchymal stem cells (MSCs) have been described as promising cell sources for cartilage repair, the present study was designed to examine whether intra-articular injection of scaffold-free adipose-derived stem cells (ASCs) obtained from subcutaneous adipose tissue could restore the matrix of arthritic knee joints in mature animals. OA was induced in adult white New Zealand rabbits by unilateral anterior cruciate ligament transection (ACLT); the contralateral knee was considered the sham-operated group. At 12 weeks following surgery, the ASCs treated group was injected intra-articularly with a single dose of 1 × 106 cells suspended in 1 mL of medium. The control group received 1 mL of medium without cells and the sham-operated group received no treatment. All rabbits were sacrificed at 16 and 20 weeks after surgery. OA progression was evaluated radiologically, grossly, and histologically using hematoxylin and eosin, Safranin-O, and toluidine blue staining.At 12 weeks after surgery all knees subjected to ACLT showed radiological signs of OA. The findings showed significant differences in the quality of cartilage between ASCs-injected group compared to control group, particularly at 20 weeks after surgery.This study suggests that ASCs obtained from subcutaneous adipose tissue could be a viable approach for treating OA.