Effects of melatonin on disease improvement and serum levels of pro-inflammatory cytokines in patients with non-atypical endometrial hyperplasia.

BACKGROUND: Endometrial hyperplasia (EH), an abnormal proliferation of the endometrial cells, is considered as one of the most common causes of abnormal uterine bleeding. Previous studies have reported that melatonin plays a fundamental role in disease treatment. This study aimed the comparison of the effects of progesterone, as the most common therapeutic approach, and melatonin with progesterone alone in improvement of non-atypical endometrial hyperplasia (NEH) and changes in pro-inflammatory cytokine levels. METHODS: Study population consisted of 40 patients with NEH. Patients were divided into two groups, including 20 subjects treated with melatonin and progesterone and 20 individuals treated with progesterone alone. The blood and endometrial sampling was performed from participants before and after a three-month treatment. The histological examination was microscopically done. The serum levels of tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) were measured using ELISA. RESULTS: There was no significant difference in the diabetes status and mean age between patients treated with progesterone and melatonin and those treated with progesterone alone. The improvement rate in the EH was significantly higher in individuals treated with progesterone and melatonin than those treated with progesterone alone (p < 0.05). Additionally, the patients treated with progesterone and melatonin showed significant increases inIFN-γ and TNF-αlevels compared to the control group (p < 0.001-P < 0.05). CONCLUSION: Melatonin supplementation has a beneficial effect in the treatment of EH due perhaps to enhance the level of IFN-γ and TNF-α.

Skin and ophthalmic complications of chloroquine and hydroxychloroquine in patients with rheumatoid arthritis and systemic lupus erythematous.

Immunosuppressive agents are routinely used to control autoimmunity. However, some adverse events are correlated to their clinical applications. The aim of this study was to study the clinical findings and ocular and cutaneous side effects of chloroquine (CQ) and hydroxychloroquine (HCQ), as current immunomodulators, in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). This descriptive study was performed on 360 individuals referred to the Rheumatology clinic during 2003-2020. Demographic characteristics and other information were collected from patients with RA and SLE. Skin and ocular complications were evaluated in patients who were on treatment with CQ and HCQ. Study populations consisted of 199 subjects with RA and 161 cases with SLE. The frequencies of skin and ocular complications in all patients treated with CQ and HCQ were 32 (17.65%) and 94 (51.9%), respectively. The prevalence of skin complications in patients with RA and SLE was 20 (10.05%) and 22 (13.66%), respectively. The frequencies of ocular complications in patients with RA and SLE were, respectively, 58 (29.4%) and 36 (22.5%). Multiple logistic regression analysis revealed that ophthalmic complications of CQ and HCQ in all patients were dependent on the effects of the duration of drug uses, disease duration, and cumulative doses (p < 0.05), unlike skin complications. Disease types had no effect on ocular complications. Based on these findings, treatment with CQ and HCQ participates in some skin and ocular complications in patients with RA and SLE which are largely associated with the duration of disease and treatment.

Human umbilical cord mesenchymal stem cells: Heralding an effective treatment against esophageal cancer?

Esophageal cancer (EC), as one of the leading causes of cancer-associated mortality, influences a remarkable population of subjects globally and is histologically divided into two types, comprising esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC). Although several therapeutic approaches are present for EC, such as radiotherapy, chemotherapy, and surgery, these options have low success with serious side effects, for example, gastrointestinal toxicity, esophagitis, and pulmonary complications. Thus, utilizing an effective tool with low side effects is urgent. Newly, mesenchymal stem cells (MSCs) have received special interest for treating diverse diseases, such as cancer. Among different sources of MSCs, human umbilical cord MSCs have notable benefits, and reports expressed that they may be effective in EC treatment. For this purpose, in this review study, we aimed to summarize evidence regarding the effects of human umbilical cord MSCs on EC with a mechanistic insight.

Effect of Humulus lupulus L. (Hop) on Postmenopausal Sexual Dysfunction: A Randomized Clinical Trial.

Objective: Female sexual dysfunction is a common distressing problem among women, which may result from reducing circulating endogenous estrogen. Humulus lupulus L. (hop) has antioxidant, anti-inflammatory, anticancer, and estrogenic properties. Therefore, this study aimed to assess the efficacy of hop on postmenopausal sexual dysfunction. Methods: In the current randomized clinical trial, study populations consisted of 63 postmenopausal women who were randomly categorized into two groups. In the hop group (N = 33), women received the vaginal gel containing Hop extract every day for seven days and then continued for two months, twice weekly. In the estradiol group (N = 30), women were treated with vaginal estradiol (0.625 mg) over two 28-day cycles (21 days of therapy and seven days rest). The sexual function was evaluated using the Female Sexual Function Index (FSFI) questionnaire before and after intervention. Results: No statistically significant differences in FSFI scores (sexual desire, sexual arousal, vaginal lubrication, satisfaction, orgasm, sexual pain, and total FSFI) (P > 0.05) were noticed after treatment between the hop and estradiol groups. Conclusion: Vaginal hop was as effective as estradiol in improving the sexual dysfunction among postmenopausal women with no adverse events. This trial is registered with IRCT20210405050859N1.

C-reactive protein and uric acid roles in distinguishing ST-segment elevation myocardial infarction from non-ST-elevation acute coronary syndrome.

Acute coronary syndrome (ACS) is defined as a range of conditions which the blood flow to the heart was reduced or stopped. This disorder is correlated to a systemic inflammatory response and some biochemical factors. Therefore, the aim of this study was investigations of serum C-reactive protein (CRP) and uric acid levels in ST-segment elevation myocardial infarction (STEMI) and non-ST-elevation ACS (NSTE ACS), as common subtypes of ACS. Patients with ACS (n = 140) were assessed with coronary arteriography and divided into STEMI and NSTE ACS groups. The serum levels of hs-CRP and uric acid were investigated using a routine clinical chemistry analyzer. Patients with STEMI showed a significant increase in uric acid level compared to those with NSTE ACS (P < .0001). Other data indicated that hs-CRP level in patients with STEMI was significantly higher than individuals with NSTE ACS (P < .0001). Modeling analysis revealed that the increased levels of acid uric and hs-CRP in patients with STEMI were independent of the effects of age, gender, background diseases, and familial history (P < .001). The current study provides further evidence to indicate that hs-CRP and uric acid may be considered as biofactors for comparing STEMI from NSTE ACS and determining disease outcome.

Impacts of IL-27 and IL-32 in the pathogenesis and outcome of COVID-19 associated mucormycosis.

Changes in the immune system participate in the pathogenesis and development of infectious diseases. Previous studies have indicated immune dysregulation in patients suffering from COVID-19 and mucormycosis. Therefore, this study investigated whether interleukin-27 (IL-27) and interleukin-32 (IL-32) levels may participate in the development and outcome of COVID-19 associated mucormycosis (CAM). The blood samples were obtained from 79 patients suffering from COVID-19 and mucormycosis and 25 healthy subjects. The serum samples were isolated from the whole blood and frequencies of some immune cells were measured by a cell counter. The levels of IL-27 and IL-32 were assessed by enzyme-linked immunosorbent assay. IL-27 and IL-32 levels were significantly lower in patients with COVID-19 and mucormycosis than healthy subjects (P < .05), although there was no significant difference in IL-27 between patients with COVID-19 and CAM. IL-27 level was significantly higher in severe COVID-19 survivors than dead cases (P < .01). Patients with CAM had significant increases in NLR compared to COVID-19 patients and healthy individuals (P < .0001-0.01). NLR was significantly associated with COVID-19 outcome (P < .05). Severe COVID-19 survivors had a significant reduction in NLR compared to non-survivors (P < .05). Changes in IL-27 and IL-32 levels may contribute to the pathogenesis of CAM. IL-27 may relate to the pathogenesis and outcomes of mucormycosis in COVID-19 patients.

Effects of Isoflavone Supplementation on the Response to Medroxyprogesterone in Premenopausal Women with Nonatypical Endometrial Hyperplasia: A Randomized, Double-Blind, Placebo-Controlled Trial.

Objective: The purpose of this study was to evaluate the impact of isoflavone supplementation compared with placebo on endometrial histology and serum estradiol levels in premenopausal women with nonatypical endometrial hyperplasia. Materials and Methods: The present double-blindplacebo-controlled clinical trial was conducted on 100 women with nonatypical endometrial hyperplasia in the age range of 30 to 45 years. Participants were randomly assigned to receive 50 mg of isoflavone (n = 50) or placebos (n = 50) daily for three months. Both groups received the standard treatment of nonatypical endometrial hyperplasia. Endometrial biopsy and blood samples were taken at the baseline and three months after the intervention. The incidence of drug side effects was assessed as well. Results: After three months, 88.4% of isoflavone-administered subjects had a significant histological improvement compared to 68.9% subjects in the placebo group (P=0.02). There were no significant differences between the two groups in the changes of serum estradiol levels and the incidence of drug side effects. Conclusion: The findings of the present study demonstrated that the coadministration of 50 mg of isoflavones and medroxyprogesterone acetate increases the treatment efficacy in women with nonatypical endometrial hyperplasia. Clinical Trial Registration. This trial was registered on the Iranian website for clinical trial registration (https://www.irct.ir/trial/53553).

Impact of oligomerization on the allergenicity of allergens.

Type I hypersensitivity (allergic reaction) is an unsuitable or overreactive immune response to an allergen due to cross-link immunoglobulin E (IgE) antibodies bound to its high-affinity IgE receptors (FcεRIs) on effector cells. It is needless to say that at least two epitopes on allergens are required to the successful and effective cross-linking. There are some reports pointing to small proteins with only one IgE epitope could cross-link FcεRI-bound IgE through homo-oligomerization which provides two same IgE epitopes. Therefore, oligomerization of allergens plays an indisputable role in the allergenic feature and stability of allergens. In this regard, we review the signaling capacity of the B cell receptor (BCR) complex and cross-linking of FcεRI which results in the synthesis of allergen-specific IgE. This review also discusses the protein-protein interactions involved in the oligomerization of allergens and provide some explanations about the oligomerization of some well-known allergens, such as calcium-binding allergens, Alt a 1, Bet v 1, Der p 1, Per a3, and Fel d 1, along with the effects of their concentrations on dimerization.

Can mesenchymal stem cells derived from adipose tissue and their conditioned medium improve ovarian functions? A mini-review.

Stable ovarian function is a key factor in the performance of the reproductive system. In contrast, some ovarian function-related diseases, such as polycystic ovarian syndrome, premature ovarian failure (POF), and ovarian cancer, are the main cause of infertility and death of women around the world. Despite multiple attempts, there are no effective tools against these conditions; however, mesenchymal stem cell-based therapy, especially using adipose tissue, has attracted much attention in medicine in light of its advantages such as easy isolation and accessibility. Conversely, it has been suggested that MSC-conditioned medium (CM) can restore injured tissues and has high immunocompatibility. So, here, we will summarize the effects of administration of MSCs and CM derived from adipose tissue on ovarian functions and related diseases.

Characterizing the immune responses of those who survived or succumbed to COVID-19: Can immunological signatures predict outcome?

BACKGROUND: Immunodeficiency has pivotal role in the pathogenesis of coronavirus disease 2019 (COVID-19). Several studies have indicated defects in the immune system of COVID-19 patients at different disease stages. Therefore, this study investigated whether alters in immune responses of COVID-19 patients may be considered as predicting factors for disease outcome. METHODS: The percentages of innate and adoptive immune cells in the recovered and dead patients with COVID-19, and healthy subjects were determined by flow cytometry. The levels of pro- and anti-inflammatory cytokines and other immune factors were also measured by enzyme-linked immunosorbent assay. RESULTS: At the first day of hospitalization, the frequencies of CD56dim CD16+ NK cells and CD56bright CD16dim/- NK cells in patients who died during treatment were significantly increased compared to recovered and healthy individuals (P < 0.0001). The recovered and dead patients had a significant increase in monocyte number in comparison with healthy subjects (P < 0.05). No significant change was observed in Th1 cell numbers between the recovered and dead patients while Th2, Th17 cell, and Treg percentages in death cases were significantly lower than healthy control and those recovered, unlike exhausted CD4 + and CD8 + T cells and activated CD4 + T cells (P < 0.0001-0.05). The activated CD8 + T cell was significantly higher in the recovered patients than healthy individuals (P < 0.0001-0.05). IL-1α, IL-1ß, IL-6, and TNF-α levels in patients were significantly increased (P < 0.0001-0.01). However, there were no differences in TNF-α and IL-1ß levels between dead and recovered patients. Unlike TGF-ß1 level, IL-10 was significantly increased in recovered patients (P < 0.05). Lymphocyte numbers in recovered patients were significantly increased compared to dead patients, unlike ESR value (P < 0.001-0.01). CRP value in recovered patients significantly differed from dead patients (P < 0.001). CONCLUSION: Changes in frequencies of some immune cells and levels of some immune factors may be considered as predictors of mortality in COVID-19 patients.

Modulation of Th17 Proliferation and IL-17A Gene Expression by Acetylated Form of Apigenin in Patients with Multiple Sclerosis.

The presence of Th17 cells in CNS lesion of MS patients due to their inflammatory cytokines secretion is in line with the deterioration of the disease. Currently, the use of natural compounds with anti-inflammatory properties such as flavonoids have been considered to reduce inflammation in these patients, but the remaining issue is how deliver these compounds to the site of inflammation. Acetylation is a way to better uptake compound by cells and cross through cellular layers with tight junctions. This study aimed to investigate the in vitro effects of the Apigenin 3-Acetate on Th17 cells of MS patients and compare its efficacy with Apigenin and Methyl Prednisolone Acetate. IC50 for Apigenin 3-Acetate, and Methyl Prednisolone Acetate were determined using three healthy volunteers. The peripheral blood mononuclear cells (PBMCs) of five MS patients were isolated and co-cultured with a selected dose of Apigenin, Apigenin 3-Acetate, and Methyl Prednisolone Acetate for 48 hr, and then theproliferation of Th17 cells in isolated PBMCs was assessed by flow cytometry. The levels of RAR-related orphan receptor (RORC) and IL-17A expression were also determined by quantitative real-time PCR. The results showed that Apigenin 3-Acetate inhibited Th17 cells proliferation (P value: 0.018) at 80 µM concentration after 48 hr. Additionally, IL-17A gene expression significantly (P value≤ 0.0001) inhibited by Apigenin, Apigenin 3-Acetate and Methyl Prednisolone Acetate in 80 µM, 80 µM and 2.5 µM (selected dose in IC50 determination) respectively These results demonstrate that Acetate increases anti-inflammatory effects of Apigenin on Th17 cells.

Programmed cell death 1 (PDCD1) gene haplotypes and susceptibility of patients to basal cell carcinoma.

Programmed death-1 (PD-1), as an immunoinhibitory receptor encoded by programmed cell death-1 (PDCD1) gene, has a pivotal role in tolerance to self-antigens. Mutations of PDCD1 may participate in susceptibility to basal cell carcinoma (BCC) as the most common of skin cancer. We studied the impacts of two single nucleotide polymorphisms (SNPs) within PDCD1 and their haplotypes in BCC susceptibility in an Iranian population. The blood samples were collected from 210 BCC and 220 healthy individuals. After the extraction of genomic DNA, the genotypes and alleles of PD1.1 G/A (rs36084323) and PD1.6 G/A (rs10204525) SNPs were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Four haplotypes were estimated by these SNPs. Our data revealed that genotype and allele frequencies of PD1.1 and PD1.6 polymorphisms in BCC patients were similar to those in healthy individuals. The results of estimated haplotypes for PDCD1 indicated that GG and AA haplotypes of PDCD1 had protective effects on BCC susceptibility (OR = 0.7, 95% CI = 0.51-0.96, p = 0.03 and OR = 0.57, 95% CI = 0.35-0.91, p = 0.02, respectively), while GA and AG haplotypes served as the risk factors for developing BCC (OR = 1.76, 95% CI = 1.09-2.84, p = 0.02 and OR = 3.87, 95% CI = 1.95-7.69, p = <0.001, respectively). Based on these findings, frequency distributions of PDCD1 haplotypes have important roles in the determination of BCC development in the Iranian population. However, larger multicenter studies are required to confirm this conclusion.

The expression levels of MicroRNA-146a, RANKL and OPG after non-surgical periodontal treatment.

OBJECTIVE: MicroRNA-146a (miR-146a) is a regulator of inflammatory response. Periodontitis is a disease with immune pathophysiology of the periodontium in which the inflammation results in the destruction of the soft tissues and alveolar bone. Therefore, the aim of this study was to investigate the expressions of miR-146a, OPG, and RANKL in diseased and healthy periodontal tissues to understand whether miR-146a expression level may associate with OPG and RANKL mRNA levels and OPG/RANKL ratio after non-surgical periodontal treatment. METHODS: The levels of miR-146a, RANKL, and OPG in gingival tissues from patients with generalized periodontitis stages II and III and grades A and B (n = 15, group A), patients with generalized periodontitis stages III and IV and grade C (n = 15, group B), and healthy individuals (n = 10) were determined by real-time PCR. The associations of miR-146a expression with OPG and RANKL levels were evaluated. RESULTS: The levels of miR-146a in two subgroups within periodontitis patients were significantly higher than healthy subjects (P < 0.0001). MiR-146a showed the increased level in group A of patients compared with group B (P < 0.05). Clinical parameters such as probing depth (PD) and clinical attachment loss (CAL) were significantly higher in patients than control group (P < 0.05). The levels of OPG and RANKL were increased in patients compared with healthy subjects, although the elevated levels were not statistically significant. MiR-146a was not associated with OPG and RANKL levels and OPG/RANKL ratio. CONCLUSIONS: The results of this study failed to show the associations of miR-146a level with OPG and RANKL levels and OPG/RANKL ratio in periodontitis after non-surgical periodontal treatment.

Effects of the programmed cell death 1 (PDCD1) polymorphisms in susceptibility to systemic lupus erythematosus.

The failure of immunological tolerance to self-antigens plays a fundamental role in the pathogenesis of systemic lupus erythematosus (SLE). PD-1 is an inhibitory receptor for regulating the immune system and preventing development of autoimmune disorders. This study aimed to determine the role of four single-nucleotide polymorphisms (SNPs) within programmed cell death 1 (PDCD1 or PD-1) gene and haplotypes defined by these SNPs in susceptibility to SLE in the Iranian population. Blood samples were obtained from 253 SLE and 564 healthy subjects. Red blood cells were lysed and genomic DNAs were extracted using salting-out method. Genotype determinations of PD1.1, PD1.3, PD1.5 and PD1.9 SNPs were performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and 12 haplotypes were constructed by PDCD1 SNPs. Our results showed significant differences in PD1.5 genotype frequencies between patient and control groups (p < .001). The frequencies of PD1.5 C/C, C/T and T/T genotypes versus other genotypes in SLE patients significantly differed from healthy subjects (p < .001, p = .001 and p = .002, respectively). Allelic analysis indicated a significant association between the frequency of PD1.5C allele and development of SLE in our population (odds ratio [OR] = 1.91, 95% confidence interval [CI] = 1.51-2.42, p < .001). At the haplotype level, GGCC, GACT and GGCT haplotypes were significantly different between SLE and control groups (OR = 2.14, 95% CI = 1.73-2.66, p < .001; OR = 9.76, 95% CI = 4.47-21.3, p < .001; and OR = 0.32, 95% CI = 0.24-0.42, p < .001, respectively). Based on these findings, PD1.5 SNP and some haplotypes of PDCD1 contribute to SLE risk in the Iranian population.

The Predicting Role of Neutrophil- Lymphocyte Ratio in Patients with Acute Ischemic and Hemorrhagic Stroke.

BACKGROUND AND AIM: The neutrophil-to-lymphocyte ratio (NLR) is considered as an independent and easy-to-measure inflammatory predictor of mortality in patients with acute stroke. However, it is unclear whether the NLR is related to other problems caused by stroke. This study evaluated the possible roles of the NLR in estimating mortality rate and health problems in patients with acute ischemic (IS) and hemorrhagic (H) stroke. METHODS: A total of 180 patients with acute IS and H stroke were enrolled. NLR was calculated from the admission blood work. Patients were divided into two groups according to the NLR values (<5 and >5). Demographic, clinical, and laboratory findings were collected for the subjects. The correlations of NLR with mortality, infection incidences, and other parameters were determined using statistical analyses. RESULTS: The percentages of lymphocytes and WBCs were significantly higher in IS stroke patients than H group, unlike neutrophil number (P < 0. 0001-0.01). In contrast with the serum levels of hemoglobin, Na, Chol, HTN, LDL, ESR, MCV, and CRP, triglyceride was significantly decreased in H group (P < 0.0001). IS group had a significant reduction in NLR (P < 0.0001). Patients with NLR of < 5 had a significant reduction in infectious diseases, unlike H group (P < 0.01). The NLR had no associations with bedscore, GIB, DVT, mortality rate. However, it was positively correlated to the numbers of WBC and RBC, and values of CRP, ESR, and hypertension (P < 0.001-0.05), unlike MCV in H group (P < 0.05). The NLR was not associated hemoglobin, triglyceride, Chol, and LDL levels. CONCLUSION: Unlike previous studies, this study suggests that the NLR, along with other clinical and laboratory parameters, may be used to determine stroke type and predict patient susceptibility to some infectious diseases such as pneumonia. However, more investigations are required to clarify the role of the NLR in different aspects of acute stroke.

Therapeutic potential of quercetin on human breast cancer in different dimensions.

BACKGROUND: There has been an extensive range of incidence and mortality of breast cancer (BC), and the comprehensively available treatments for BC have not been completely successful in achieving satisfactory outcomes up to date. HYPOTHESIS: Recently, we are watching intense attention paid to the utilization of natural compounds as a novel therapeutic strategy for cancer treatment. Quercetin, a dietary flavonol in a large group of commonly consumed foods, is widely illustrated to apply inhibitory effects on cancer progression through several mechanisms including apoptosis enhancement, cell cycle arrest, metastasis and angiogenesis inhibition, antioxidant replication and estrogen receptor modulation. METHODS: We reviewed the most relevant papers published from 2009 to 2018 (except 15 articles), using "pub med" and "web of science" and the search terms "Quercetin"; "Breast cancer"; "Flavonoid"; "Apoptosis"; "Cell cycle"; "chemotherapy"; "Drug resistance"; "Metastasis; "Oxidative stress", "Breast cancer receptors" and "Quercetin derivatives". We selected studies on the association of quercetin with breast cancer in different dimensions. RESULTS: Despite the remarkable number of studies on quercetin's efficacy, multiple aspects of this herbal compound have not been clarified well and this review provides a summarized update of the recent evidence on biologically available efficacies of quercetin which would establish a further biological basis for the potential therapeutic acquisition of quercetin as an anticancer drug. CONCLUSION: Basic, epidemiological and genetic studies point to the potential role of quercetin in the treatment of breast cancer, but randomized and controlled trials are of great importance to establish the clinical efficacy of quercetin in ill or at-risk subjects.

The Effects of Silymarin and Cyclosporine A on the Proliferation and Cytokine Production of Regulatory T Cells.

Background: Immunosuppressive agents are necessary to enhance allograft tolerance after transplantation and the treatment of autoimmune disorders. Regulatory T cells (Tregs) play a pivotal role in improving allograft tolerance and determining the fate of transplanted organs. Therefore, the aim of this study was to investigate the immunomodulatory effects of cyclosporine A (CsA) and silymarin on the proliferation and cytokine production of Tregs. Methods: Peripheral blood mononuclear cells (PBMCs) were obtained from healthy voluntaries and Tregs were isolated using an immunomagnetic separation method. The phenotypic characteristics of Tregs were determined by flow cytometry. Tregs were expanded and then cultured with different concentrations of CsA and silymarin. The effects of CsA and silymarin on the viability, proliferation, and transforming growth factor-beta 1 (TGF-ß1) production of Tregs were determined after 3 and 5 days of culture. Results: CsA significantly decreased Treg proliferation in a dose-dependent manner (p < 0.01-0.05). CsA failed to change TGF-ß1 production of Tregs. On the contrary, silymarin significantly increased the proliferation of Tregs (p < 0.01-0.05). A statistically significant increase was also observed in the TGF-ß1 production of Tregs (p < 0.01-0.05). Our data showed that Treg viability was not compromised by CsA and silymarin. Conclusion: Overall, the results of this study for the first time indicate that silymarin, unlike CsA, has the ability to increase the proliferation and TGF-ß1 production of Tregs and may be beneficial in the treatment of autoimmune disorders and improvement of Treg-dependent allograft tolerance after transplantation.

Comparison of the Percentage of Regulatory T cells and their p-STAT5 Expression in Allergic and Non-Allergic Common Variable Immunodeficiency Patients.

BACKGROUND: Common Variable Immunodeficiency (CVID) is a primary immunodeficiency characterized by an immunologic deficiency in immunoglobulin production. Regulatory T cells (Tregs) play a key role in preventing the development allergic disorders. p-STAT5 is a known factor for the function and survival of Tregs. This study aimed to investigate the number of Tregs and their p-STAT5 expression in allergic and non-allergic CVID patients. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from 10 healthy volunteers, 10 allergic patients, and 16 CVID patients (allergic and non-allergic) using Ficoll density centrifugation. The percentage of Tregs in PBMCs was analyzed by flow cytometry. Tregs were also isolated from participants using an immunomagnetic separation method and p-STAT5 expression was evaluated in Tregs using flow cytometry. RESULTS: The results revealed that Treg percentage was significantly lower in the CVID patients than the control groups (healthy and allergic individuals) (p<0.001). There was a significant reduction in Treg percentage in allergic patients compared to healthy subjects (p<0.05). No significant difference in Treg percentage between allergic and non-allergic CVID patients was observed. The expression of p-STAT5 in Tregs was significantly lower in CVID patients than the control groups (p<0.001). In addition, the expression of p-STAT5 in Tregs of allergic patients was significantly decreased compared to healthy subjects (p<0.001). However, the deference of p-STAT5 level was not statistically significant between allergic and non-allergic CVID patients. CONCLUSION: These findings suggest that p-STAT5 signaling defect and decreased Treg number may not participate in the development of allergy in CVID patients.

Association of programmed death-1 gene polymorphisms with the risk of basal cell carcinoma.

Environmental and genetic factors play a fundamental role in the pathogenesis of basal cell carcinoma (BCC) defined as the most common cancer of skin. Programmed death-1 (PD-1), encoded by programmed cell death-1 (PDCD1) gene, serves as an inhibitory molecule in the suppression of immune responses and a risk factor in the development of different cancers. In this study, we investigated the role of two single nucleotide polymorphisms (SNPs) within PDCD1 gene, and haplotypes defined by these SNPs, in the development of BCC in an Iranian population. Whole blood samples were obtained from 210 BCC and 320 healthy subjects. Genomic DNA was extracted from whole blood samples, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to genotype determinations of PD1.3 (rs11568821) and PD1.5 (rs2227981) SNPs, and 4 haplotypes were constructed by PDCD1 SNPs. The frequency of G allele of PD1.3 was significantly higher in BCC patients than healthy subjects (p < 0.02), while these significant differences were not observed in the frequencies of PD1.5 alleles between BCC and healthy subjects. Moreover, we found that there were no statistically significant differences in PD1.3 and PD1.5 genotypes between BCC and control groups. Of all estimated haplotypes for PDCD1, only AC haplotype was associated with BCC (OR = 0.22, 95% CI = 0.06-0.79, p < 0.01). These findings suggest that PD1.3G allele and AC haplotype of PDCD1 contribute to BCC in the Iranian population. However, further studies in different populations with larger sample size are required to confirm this study.

Toll-like receptor 4 activation on human amniotic epithelial cells is a risk factor for pregnancy loss.

BACKGROUND: Maternal-fetal tolerance plays a fundamental role in the maintenance of pregnancy. However, this immunological tolerance can be influenced by intrauterine infections. Human amniotic epithelial cells (hAECs) have immunomodulatory effects and respond to invading pathogens through expressing various toll-like receptors (TLRs). We hypothesize that bacteria or bacterial products affect the immunosuppressive effects of hAECs through TLR stimulation. Here, we investigated how a successful pregnancy can be threatened by TLR4 activation on hAECs on lipopolysaccharide (LPS) engagement. MATERIALS AND METHODS: hAECs were isolated from the amniotic membrane received from six healthy pregnant women. The immunophenotyping of hAECs was studied by flow cytometry. The isolated hAECs (4 × 105 cells/ml) were cultured in 24-well plates in the presence or absence of LPS (5 µg/ml). After 24, 48, and 72 h of incubation, the culture supernatants of hAECs were collected, and the levels of interleukin-5 (IL-5), IL-6, IL-1ß, tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta 1 (TGF-ß1), and prostaglandin E2 (PGE2) were measured by enzyme-linked immunosorbent assay. RESULTS: TLR4 activation showed a stimulatory effect on TGF-ß1 production of hAECs (P < 0.001-0.05). PGE2 production of LPS-stimulated hAECs was significantly increased (P < 0.01-0.05). Moreover, TLR4 could induce TNF-α and IL-1ß production of hAECs (P < 0.0001-0.01), while this effect was not observed on IL-6 production of hAECs. The IL-5 was produced at a very low level in two culture supernatants of hAECs, in which its production was independent of LPS effect. CONCLUSION: TLR4 activation by bacterial components on hAECs may be a potential risk factor for pregnancy complications.