Contradictory Effect of Lymphocyte Therapy and Prednisolone Therapy on CD3+CD8+CD56+ Natural Killer T Population in Women with Recurrent Spontaneous Abortion.

Background: Natural killer T (NKT) cells are influential immune cells in pregnancy failures, including recurrent spontaneous abortion (RSA). Different approaches are used for these disorders due to their effects on maternal immunomodulation. Aims: In the present study, we compared the effects of two typical immunotherapies (lymphocyte immunotherapy [LIT] and low-dose prednisolone) on CD3+CD56+CD16+ and CD3+CD56+CD8+ cells as two distinct subsets of NKT cells in Women with RSA. Settings and Design: This study was a comparative cohort study conducted from 2021 to 2022. One hundred and five women with RSA were distributed into three treatment groups randomly. Materials and Methods: Fifty women in the group of low-dose prednisolone therapy, fifty women in the LIT group and five women without any treatment as the control group were included in the study. NK and NKT cell subsets were assessed using flow cytometry. Furthermore, the concentration of interferon-gamma (IFN-γ), transforming growth factor-beta (TGF-ß) and interleukin-10 (IL-10) was measured quantitatively using the enzyme-linked immunosorbent assay technique. Statistical Analysis Used: Normality and comparisons between study groups were performed by non-parametric unpaired Mann-Whitney, Kruskal-Wallis rank sum test, and one-way ANOVA. Results: The percentage of CD56dim NK cells was increased after prednisolone therapy, while this population significantly decreased in the LIT group. In contrast to the LIT group, the administration of prednisolone increased CD3+CD8+CD56+ NKT cells (P < 0.0001), which is helpful for pregnancy. The effect of the investigated treatment approaches on the population of peripheral CD3+CD56+CD16+ NKT cells of women with RSA was not adequately significant. The same situation was also observed regarding the serum level of IFN-γ. However, a significant decrease in serum levels of IL-10 and TGF-ß was observed after prednisolone therapy. Conclusion: The lower capability of LIT in changing the population of NKT cells compared to prednisolone therapy may be due to its mechanism of action, which is related to the production of blocking antibodies. These treatment approaches had different effects on NKT cells, indicating that NKT cell population and function can be affected using LIT and prednisolone therapy distinctly. In addition, prednisolone therapy and LIT in women with normal serum levels of IFN-γ have no harmful effects in changing the production of this critical cytokine.

Inflammatory Responses of Women with Polycystic Ovary Syndrome in Vitro Differ from Healthy Women.

Polycystic ovary syndrome is a low-grade inflammatory state with increased serum levels of TNF-α. The present study has compared the inflammatory responses to breast cancer cell lines in women with PCOS with healthy women. Peripheral blood mononuclear cells (PBMCs) isolated from 50 women with PCOS and 50 healthy controls were cultured in the trans-well co-culture system. These cells were stimulated with two distinct breast cancer cell lines. The proliferation of PBMCs, CD3+CD8+T cell percentages, and tumor necrosis factor-alpha (TNF-α) concentration were evaluated after 48 and 72 hours of incubation. TNF-α concentration and the proliferation rate of PBMCs after 48 hours of incubation significantly increased in the PCOS group. However, after 72 hours, TNF-α secretion significantly decreased in the PCOS group. The ability of PBMCs to produce TNF-α decreased gradually in women with PCOS. When the effects of low-grade inflammation and endocrine conditions on the cells decrease, the inability of PBMCs to create an inflammatory response will be altered.

Blockade of exosome release alters HER2 trafficking to the plasma membrane and gives a boost to Trastuzumab

Objective(s) Exosomal HER2 has been evidenced to interfere with antibody-induced anti-tumor effects. However, whether the blockade of HER2+ exosomes release would affect antibody-mediated tumor inhibition has yet to be investigated. Methods Exosomes derived from BT-474, SK-BR3 and SK-OV3 (HER2-overexpressing tumor cells) and MDA-MB-231 cells (HER2 negative) were purified and characterized by bicinchoninic acid (BCA) assay, western blotting and Transmission electron microscopy (TEM). Inhibition of exosome release was achieved by neutral sphingomyelinase-2 (nSMase-2) inhibitor, GW4869. The effects of exosome blockade on the anti-proliferative effects, apoptosis induction, and antibody-mediated cellular cytotoxicity (ADCC) activity of Trastuzumab were examined using MTT, flow cytometry, and LDH release assays. Also, the effects of exosome inhibition on the surface expression and endocytosis/internalization of HER2 were studied by flow cytometry. Results Purified exosomes derived from HER2 overexpressing cancer cells were positive for HER2 protein. Blockade of exosome release was able to significantly improve apoptosis induction, anti-proliferative and ADCC responses of Trastuzumab dose dependently. The pretreatment of Trastuzumab/purified NK cells, but not PBMCs, with HER2+ exosomes could also decrease the ADCC effects of Trastuzumab. Exosome inhibition also remarkably downregulated surface HER2 levels in a time-dependent manner, but does not affect its endocytosis/internalization. Conclusion Based on our findings, HER2+ exosomes may benefit tumor progression by dually suppressing Trastuzumab-induced tumor growth inhibition and cytotoxicity of NK cells. It seems that concomitant blocking of exosome release might be an effective approach for improving the therapeutic effects of Trastuzumab, and potentially other HER2-directed mAbs (AU)

Potential Therapeutic Effects of Human Amniotic Epithelial Cells on Gynecological Disorders Leading to Infertility or Abortion.

The induction of feto-maternal tolerance, fetal non-immunogenicity, and the regulation of mother's immune system are essential variables in a successful pregnancy. Fetal membranes have been used as a source of stem cells and biological components in recent decades. Human amniotic epithelial cells (hAEC) have stem/progenitor characteristics like those found in the amniotic membrane. Based on their immunomodulatory capabilities, recent studies have focused on the experimental and therapeutic applications of hAECs in allograft transplantation, autoimmune disorders, and gynecological problems such as recurrent spontaneous abortion (RSA), recurrent implantation failure (RIF), and premature ovarian failure (POF). This review discusses some of the immunomodulatory features and therapeutic potential of hAECs in preventing infertility, miscarriage, and implantation failure by controlling the maternal immune system.

Blockade of exosome release alters HER2 trafficking to the plasma membrane and gives a boost to Trastuzumab.

OBJECTIVE(S): Exosomal HER2 has been evidenced to interfere with antibody-induced anti-tumor effects. However, whether the blockade of HER2+ exosomes release would affect antibody-mediated tumor inhibition has yet to be investigated. METHODS: Exosomes derived from BT-474, SK-BR3 and SK-OV3 (HER2-overexpressing tumor cells) and MDA-MB-231 cells (HER2 negative) were purified and characterized by bicinchoninic acid (BCA) assay, western blotting and Transmission electron microscopy (TEM). Inhibition of exosome release was achieved by neutral sphingomyelinase-2 (nSMase-2) inhibitor, GW4869. The effects of exosome blockade on the anti-proliferative effects, apoptosis induction, and antibody-mediated cellular cytotoxicity (ADCC) activity of Trastuzumab were examined using MTT, flow cytometry, and LDH release assays. Also, the effects of exosome inhibition on the surface expression and endocytosis/internalization of HER2 were studied by flow cytometry. RESULTS: Purified exosomes derived from HER2 overexpressing cancer cells were positive for HER2 protein. Blockade of exosome release was able to significantly improve apoptosis induction, anti-proliferative and ADCC responses of Trastuzumab dose dependently. The pretreatment of Trastuzumab/purified NK cells, but not PBMCs, with HER2+ exosomes could also decrease the ADCC effects of Trastuzumab. Exosome inhibition also remarkably downregulated surface HER2 levels in a time-dependent manner, but does not affect its endocytosis/internalization. CONCLUSION: Based on our findings, HER2+ exosomes may benefit tumor progression by dually suppressing Trastuzumab-induced tumor growth inhibition and cytotoxicity of NK cells. It seems that concomitant blocking of exosome release might be an effective approach for improving the therapeutic effects of Trastuzumab, and potentially other HER2-directed mAbs. In addition, the exosome secretion pathway possibly contributes to the HER2 trafficking to plasma membrane, since the blockade of exosome secretion decreased surface HER2 levels.

The effects of eugenol nanoemulsion on pain caused by arteriovenous fistula cannulation in hemodialysis patients: A randomized double-blinded controlled cross-over trial.

OBJECTIVES: Local anesthetic and antinociceptive activity of eugenol, as the main ingredient of clove, was determined in previous researches. This study aimed to assess the efficacy of its topical nanoemulsion gel vs. placebo in controlling pain caused by arteriovenous fistula (AVF) needling in patients undergoing hemodialysis (HD). DESIGN: In this double-blinded cross-over trial, the patients were randomly allocated to eugenol gel 4% (n = 34) and placebo gel (n  = 34) groups. For each patient, a tip of finger unit of gel was applied 2 cm around the insertion site of hemodialysis needles. After 10 min, AVF needling was done. AVF needling-related pain was assessed using visual analogue scale (VAS) immediately after the puncture. All patients were tested at three different states: (1) before using any intervention; (2) after using either the eugenol or placebo gel; and (3) after crossing over the groups. RESULTS: There was a significant difference between the mean of patients' pain severity score in the three states (p = 0.001). It was reported as low as 3.29 ±â€¯0.67 in patients who received eugenol nanoemulsion. Also, the highest pain severity score (5.03 ±â€¯0.57) was reported at the no-intervention state. CONCLUSIONS: It seems that topical application of eugenol nanoemulsion may significantly decrease AVF cannulation related pain intensity score in patients undergoing HD. However, further studies with larger sample size and longer intervention period should be done for better judgment on its efficiency and safety.

The process of responding to stigma in people with schizophrenia spectrum disorders and families: A grounded theory study.

BACKGROUND: The way people with schizophrenia spectrum disorders and families address stigma has a significant role in their vulnerability to this distressing phenomenon. However, there is little knowledge about this issue in Middle Eastern countries. PURPOSE: Exploring the process of addressing stigma in people with schizophrenia spectrum disorders and families. DESIGN AND METHODS: In our grounded theory study, we interviewed seven patients and nine family members and used a constant comparative analysis approach for data analysis. FINDINGS: The participants expressed being socially rejected and oppressed by others. In addressing stigma, the patients and families surrendered passively and reluctantly. This main strategy sometimes led to deprivation and isolation and sometimes resulted in lessening their tension. PRACTICE IMPLICATIONS: Mental health nurses can empower patients and families with the skills necessary to counter stigma and, in this way, modify the sense of disability as an obstacle to stigma resistance. Also, mental health nurses can modify the contextual factors of stigma by initiating campaigns, educating society members, and involving them in fighting stigma.

Experience and the meaning of stigma in patients with schizophrenia spectrum disorders and their families: A qualitative study.

AIM: This study aimed to explore the experiences of stigma in patients with schizophrenia spectrum disorders and their families. METHODS: This qualitative content analysis study was carried out in 2016-2017 in a psychiatric hospital in Tehran, Iran. A total of 16 patients with schizophrenia spectrum disorders and their families were chosen purposefully. In order to collect the data, unstructured interviews were conducted. For the data analysis, an inductive content analysis approach was used. RESULTS: The data analysis led to the formation of two categories, "being socially rejected" and "being oppressed by others," and nine subcategories. In being socially rejected, others do not have a desire to communicate and start or continue cohabitation with the patients and their families and stay at a distance from them with fear. In being oppressed by others, persons behave aggressively with the patients and their families, violate their rights, and humiliate and ridicule them with their incorrect judgment. CONCLUSIONS: Patients with schizophrenia spectrum disorders and their families have the unpleasant and upsetting experiences of stigma. This problem imposes pressures and extreme difficulties on them, besides the difficulties related to the nature and the symptoms of the disorder. The findings reveals the need to develop strategies to help patients and their families effectively encounter stigma.

The Roles of T Helper 1, T Helper 17 and Regulatory T Cells in the Pathogenesis of Sarcoidosis.

Sarcoidosis is a systemic granulomatous disorder of unidentified etiology, with a heterogeneous clinical presentation. It is characterized by a reduced delayed-type hypersensitivity to tuberculin and common antigens. The balance between Th1, Th17 and Regulatory T(Treg) cells controls T-cell proliferation and activation.The Th17/Treg ratio in the peripheral blood and bronchoalveolar lavage fluidis increased in patients with active sarcoidosis. Amplified IL-17A expression in granulomas and the presence of IL-17A+, IL-17A+IL-4+ and IL-17A+IFN-γ+ memory T helper cells in the circulation and BAL indicate Th17 cell involvement in granuloma induction and/or maintenance in sarcoidosis. Sarcoidosis should therefore be considered as a Th1/Th17 multisystem disorder and anti-IL-17/Th17 approaches that control and reduce IL-17Amay be an option, therefore, for the treatment of sarcoidosis.Here we provide a short overview as to the role of Th17 cells as critical cells in the pathogenesis of sarcoidosis.

The Level of Depression and Assertiveness among Nursing Students.

BACKGROUND: Nursing students are susceptible to a higher risk of depression. Recognition of depression, assertiveness and the relationship between them is important since if a relationship exists, probably enhancing the level of assertiveness can reduce depression in this high risk group. We aimed to investigate depression and assertiveness levels and the relationship between them in nursing students of Tehran University of Medical Sciences. METHODS: The target population of this cross-sectional study was bachelor nursing students of Tehran University of Medical Sciences, as the largest and one of the most prestigious Iranian universities. For selecting samples, the convenience sampling method was used. Having no previous information about classes, the researcher selected the students from the courses held while the researcher was present for sampling at the faculty and studied all the students willing to participate in the study in selected classes. The questionnaire consisted of demographic information, Gambrill and Richey assertion inventory, and Beck's depression inventory. SPSS software, version 16, was used to analyze the data. ANOVA and independent samples t test were used for as appropriated. RESULTS: 55.6% of students indicated average and low levels of assertiveness and 38.7% were suffering from mild to severe depression. Pearson correlation test showed a significant inverse relationship (r=0.314 and P<0.001) between assertiveness and depression. There were significant relationships between depression and interest in the field of study (P=0.001) and between assertiveness and gender (P=0.035). CONCLUSION: There was an inverse significant relationship between depression and assertiveness among nursing students. We suggest a cohort study design that can determine the effect of these variables on each other completely.

Self-efficacy after life skills training: a case-control study.

BACKGROUND: Nursing students' self-efficacy is a predictor for their educational progress. Students, who believe that they can be successful in their studies, are more confident. Therefore, many universities have focused on life skills training programs to improve the mental health of their students. OBJECTIVES: This study was conducted to evaluate and compare self-efficacy in two groups of nursing students of Tehran University of Medical Sciences (TUMS). One group of students was trained on life skill programs, and the second group was not trained on the issue. MATERIALS AND METHODS: A case-control study was conducted on two groups of nursing students in TUMS in the late 2012. The case group (n = 112) had passed life skills training course, and the control group (n = 139) was not trained on the issue. Data was collected using a questionnaire containing 12 questions about demographic features, and the Sherer's general self-efficacy questionnaire. Data analysis was performed using independent sample t-test, Chi-square, odds ratio, and Fisher's exact test. RESULTS: In the untrained and trained groups, 23% and 8% of the students had very high self-efficacy, respectively. The overall mean scores of self-efficacy were 41.99 ± 9.31 and 38.99 ± 10.48 in the trained and untrained groups, respectively (P = 0.015), and the higher mean score indicates lower level of self-efficacy. A significant difference was also found between the self-efficacy and family income (P = 0.029). CONCLUSIONS: The present study showed that life skills training program did not affect self-efficacy of nursing students. Perhaps, the methods used in education were influencing and then, more effective techniques such as role-play and group discussion should be substituted in life skills training.