Evaluation of HLA-DR and HLA-DQ expression in gastric cancer tissues.

BACKGROUND AND OBJECTIVES: Despite recent advances in understanding the gastric cancer (GC) biology, the precise molecular mechanism of gastric carcinogenesis and role of deregulated immune responses in GC progression are still not well understood. In this study, mRNA levels of human leukocyte antigen (HLA)-DRA and -DQA1 were assessed in GC patients to find a potential association between expression of these HLA-II molecules and gastric carcinogenesis. METHODS: Using quantitative real-time (qRT)-PCR, mRNA levels of HLA-DRA and -DQA1 were assessed in 20 pairs of matched GC and normal tissues. RESULTS: Our results showed that overall mRNA level of HLA-DRA was decreased in the tumor samples relative to control tissues (median fold change [FC] = 0.693; P = 0.445). Overall HLA-DQA1 level was increased in the tumor samples relative to control tissues (median FC = 1.659; P = 0.5117). However, the mentioned data were not statistically significant. Meanwhile, using a ≥ 2.5 FC as the cutoff to determine upregulation or downregulation, 35% of patients showed a downregulated expression of HLA-DRA, while 10% of those showed upregulation in HLA-DRA expression. Upregulation and downregulation of HLA-DQA1 expression were detected, respectively, in 35% and 25% of samples. A strong positive correlation was determined between HLA-DRA and HLA-DQA1 levels in tumor tissues (r = 0.7298; P = 0.0003). CONCLUSION: The results reported here along with future studies can be useful to understand the interplay between immune system and GC, therefore, may be helpful to design an effective immune-based therapy.

Comparison of neutralization potency across passive immunotherapy approaches as potential treatments for emerging infectious diseases.

The use of passive immunotherapy, either as plasma or purified antibodies, has been recommended to treat the emerging infectious diseases (EIDs) in the absence of alternative therapeutic options. Here, we compare the neutralization potency of various passive immunotherapy approaches designed to provide the immediate neutralizing antibodies as potential EID treatments. To prepare human plasma and purified IgG, we screened and classified individuals into healthy, convalescent, and vaccinated groups against SARS-CoV-2 using qRT-PCR, anti-nucleocapsid, and anti-spike tests. Moreover, we prepared purified IgG from non-immunized and hyperimmunized rabbits against SARS-CoV-2 spike protein. Human and rabbit samples were used to evaluate the neutralization potency by sVNT. All vaccinated and convalescent human plasma and purified IgG groups, as well as purified IgG from hyperimmunized rabbits, had significantly greater levels of spike-specific antibodies than the control groups. Furthermore, when compared to the other groups, the purified IgG from hyperimmunized rabbits exhibited superior levels of neutralizing antibodies, with an IC50 value of 2.08 µg/ml. Additionally, our results indicated a statistically significant positive correlation between the neutralization IC50 value and the positive endpoint concentration of spike-specific antibodies. In conclusion, our study revealed that purified IgG from hyperimmunized animals has greater neutralization potency than other passive immunotherapy methods and may be the most suitable treatment of critically ill patients in EIDs.

Decellularized human amniotic membrane loaded with epigallocatechin-3-gallate accelerated diabetic wound healing.

Diabetic wounds, as one of the most important complications of diabetes, face many challenges in treatment. Herein we investigated whether decellularized human amniotic membrane (dAM) loaded with epigallocatechin-3-gallate (EGCG) could promote healing in diabetic rats. Sixty diabetic rats were randomly planned into the untreated group, dAM group, EGCG group, and dAM + EGCG group. On days 7, 14, and 21, five rats from each group were sampled for stereological, molecular, and tensiometrical assessments. Our finding revealed that the wound closure rate, the total volumes of new epidermis and dermis, the numerical densities of fibroblasts, blood vessels, collagen density as well as tensiometrical parameters of the healed wounds were considerably increased in the treated groups than in the untreated group, and these changes were more obvious in the dAM + EGCG ones. Furthermore, the expression of TGF-ß, bFGF, and VEGF genes were significantly upregulated in all treated groups compared to the untreated group and were greater in the dAM + EGCG group. This is while expression of TNF-α and IL-1ß, as well as cell numerical densities of neutrophils and macrophages decreased more considerably in the dAM + EGCG group in comparison to the other groups. In conclusion, it was found that using both dAM transplantation and EGCG has more effect on diabetic wound healing.

Efficient Neural Differentiation of Mouse Embryonic Stem Cells by Mastic Gum.

Purpose: Promoting neurogenesis is a promising strategy to treat neurodegenerative disorders. In the present study, we aimed to evaluate the effect of mastic gum resin from the Pistacia lentiscus var. Chia (Anacardiaceae family) in proliferation capacity and differentiation of embryonic mesenchymal stem cells into a neural lineage. Methods: For this purpose, mastic gum was applied as a neural inducer for stem cell differentiation into the neuronal lineage. Following treatment of embryonic stem cells (ESCs) with mastic gum, verification differentiation of the ESCs into the neuronal lineage, gene expression analysis, and immunocytochemistry staining approach were performed. Results: Gene expression analysis demonstrated that mastic gum increased the expression level of neuron markers in the ESCs-derived neuron-like cells. Moreover, our immunocytochemistry staining results of two important neural stem cell markers, including Nestin and microtubule-associated protein-2 (Map2) expression confirmed that mastic gum has the potential to promote neuronal differentiation in ESCs. Conclusion: In summary, the use of mastic gum to stimulate the differentiation of ESCs into a neural lineage can be considered as a good candidate in stem cell therapy.

Drug prescription patterns and their association with mortality and hospitalization duration in COVID-19 patients: insights from big data.

Background: Different medication prescription patterns have been associated with varying course of disease and outcomes in COVID-19. Health claims data is a rich source of information on disease treatment and outcomes. We aimed to investigate drug prescription patterns and their association with mortality and hospitalization via insurance data for a relatively long period of the pandemic in Iran. Methods: We retrieved hospitalized patients' data from Iran Health Insurance Organization (IHIO) spanning 26 months (2020-2022) nationwide. Included were patients with ICD-10 codes U07.1/U07.2 for confirmed/suspected COVID-19. A case was defined as a single hospitalization event for an individual patient. Multiple hospitalizations of a patient within a 30-day interval were aggregated into a single case, while hospitalizations with intervals exceeding 30 days were treated as independent cases. The Anatomical Therapeutic Chemical (ATC) was used for medications classification. The two main study outcomes were general and intensive care unit (ICU) hospitalization periods and mortality. Besides, various demographic and clinical associate factors were analyzed to derive the associations with medication prescription patterns and study outcomes using accelerated failure time (AFT) and logistic regression models. Results: During the 26 months of the study period, 1,113,678 admissions with COVID-19 diagnosis at hospitals working in company with IHIO were recorded. 917,198 cases were detected from the database, among which 51.91% were females and 48.09% were males. Among the main groups of medications, antithrombotics (55.84% [95% CI: 55.74-55.94]), corticosteroids (54.14% [54.04-54.24]), and antibiotics (42.22% [42.12-42.32]) were the top used medications among cases with COVID-19. Investigation of the duration of hospitalization based on main medication groups showed antithrombotics (adjusted median ratio = 0.94 [0.94-0.95]) were significantly associated with shorter periods of overall hospitalization. Also, antithrombotics (adjusted odds ratio = 0.74 [95%CI, 0.73-0.76]), corticosteroids (0.97 [0.95-0.99]), antivirals (0.82 [0.80-0.83]), and ACE inhibitor/ARB (0.79 [0.77-0.80]) were significantly associated with lower mortality. Conclusion: Over 2 years of investigation, antithrombotics, corticosteroids, and antibiotics were the top medications for hospitalized patients with COVID-19. Trends in medication prescription varied based on various factors across the country. Medication prescriptions could potentially significantly impact the trends of mortality and hospitalization during epidemics, thereby affecting both health and economic burdens.

Association between White Blood Cells Count and Diabetes Mellitus in Tabari Cohort Study: A Case-Control Study.

BACKGROUND: White Blood Cells (WBC) can be a useful marker to predict diabetes. In this study, we aimed to investigate the association between WBC count with type 2 diabetes in a large-scaled population-based cohort study. METHODS: In the present study we used a subset of data collected in enrolment phase of Tabari cohort study. Participants with fasting blood glucose ≥126 or those who report as having diabetes or taking glucose-lowering medications were selected as case group (1765 participants) and control group included participants who did not report as having diabetes (1765 participants) and they randomly selected from the baseline population. Hematology indices were measured for all participants using Celltac Alpha MEK-6510 K. Chi-squared and independent t-test were used to compare categorical and continuous variables, respectively. RESULTS: The mean of WBC in diabetic patients and control group was 6.89 ± 1.67 and 6.37 ± 1.49 respectively (P ≤ 0.001). The odds of diabetes based on WBC count in crud model was 1.23 [CI 95% 1.181.28] and after adjustment for all possible confounding factor was 1.17 [CI 95% 1.111.23]. CONCLUSIONS: Results of the present study showed a significant association between WBC count and diabetes. This association remained significant after adjustment for all possible confounders.

PD-L1 overexpression conveys tolerance of mesenchymal stem cell-derived cardiomyocyte-like cells in an allogeneic mouse model.

Although the autologously transplanted cells are immunologically durable, allogeneic cell transplantation is inevitable in a series of cases. Mesenchymal stem cells (MSCs) are one of the suitable candidates for cardiac tissue regeneration that have been shown to acquire immunogenicity concurrent with cardiomyogenic differentiation. The present study aimed to exploit PD-L1, as a key immunomodulatory checkpoint ligand to protect the MSCs-derived cardiomyocyte-like cells (CLCs) against the detrimental alloimmunity. Mouse bone marrow-derived MSCs were stably transduced to overexpress PD-L1. MSCs were in vitro differentiated into CLCs and the expressions of immunologic molecules were compared between MSCs and CLCs. The in vitro and in vivo allogeneic immune responses were also examined. The differentiated CLCs had higher expressions of MHC-I and CD80. Upon in vitro coculture with allogeneic splenocytes, CLCs caused more CD4+ and CD8+ T cell activation, lymphocyte proliferation, and interferon-γ (IFN-γ) release in comparison to MSCs. PD-L1 overexpression on CLCs decreased the activation of CD8+ T cells, proliferation of lymphocytes, and release of IFN-γ. The PD-L1-overexpressing CLCs elicited lower in vivo CD4+ and CD8+ T cell activation and reduced the anti-donor antibody response accompanied by increased durability and reduced T cell infiltration. The present study verified the potential of PD-L1 overexpression as a preparative strategy for the protection of allogeneic MSCs-derived CLCs against the detrimental alloreaction.

Blood supply sufficiency and safety management in Iran during the COVID-19 outbreak.

BACKGROUND: COVID-19 first appeared in Iran on 19 February 2020, and then spread rapidly over the country. In this article, we review the action plan of the Iranian Blood Transfusion Organization with respect to this disease. METHOD AND MATERIALS: We collected data on blood donations and RBC inventory for the first 8 weeks of the outbreak. We also evaluated the trend of blood donations and RBC inventory and compared them with the data of the past year. We include a summary of actions taken by the National Committee on Management of COVID-19 outbreak. RESULTS: Blood donations decreased from 33 275 to 23 465 units during the first 2 weeks of the outbreak with a corresponding decrease in the RBC inventory. But after that, donations gradually increased from 23 465 to 29 665 units. RBC inventory levels improved at the same time. Then, the Iranian New Year's holiday resulted in another downward trend. After the holiday, blood donations revived, along with the RBC inventory. DISCUSSION: Although it appears that this virus cannot be transmitted through transfusion, changes in lifestyle had a significant impact on reducing blood supply. Following implemented measures, we saw an upward trend in blood donations and an adequate supply of RBC units in blood centres, helped by a reduction in demand by hospitals. Blood centres need to be more prepared to manage future viral disasters, especially in case of transfusion-transmissible infections.

Efficacy of mesenchymal stem cell therapy on glucose levels in type 2 diabetes mellitus: A systematic review and meta-analysis.

AIMS/INTRODUCTION: In recent years, mesenchymal cellular therapies have received much attention in the treatment of diabetes. In this meta-analysis, we aimed to evaluate the efficacy of mesenchymal stem cell therapy in type 2 diabetes mellitus patients. MATERIALS AND METHODS: A comprehensive literature search was carried out using PubMed, Scopus, Web of Science and Central databases. A total of 1,721 articles were identified, from which nine full-text clinical trials were qualified to enter the current meta-analysis. The assessment groups included patients with type 2 diabetes, and levels of C-peptide, glycosylated hemoglobin and insulin dose were analyzed before and after mesenchymal stem cell infusion. Data analysis was carried out in Stata version 11, and the Jadad Score Scale was applied for quality assessment. RESULTS: Changes in levels of C-peptide after mesenchymal stem cell therapy were: standardized mean difference 0.20, 95% confidence interval -0.61 to 1.00, glycosylated hemoglobin levels were: standardized mean difference -1.45, 95% confidence interval -2.10 to -0.79 and insulin dose were: standardized mean difference -1.40, 95% confidence interval -2.88 to 0.09. CONCLUSIONS: This meta-analysis of prospective studies showed associations between mesenchymal stem cell therapy and control of glucose level in patients with type 2 diabetes.

Mouse bone marrow-derived mesenchymal stem cells acquire immunogenicity concurrent with differentiation to insulin-producing cells.

BACKGROUND: Although mesenchymal stem cells (MSCs) are regarded as immune-elusive and even immunosuppressive, recent evidence suggests that allogeneic immune response might is inevitable in the case of some lineages differentiated from MSCs. Regarding the importance of allogeneic IPCs and MSCs in pre-clinical and clinical studies, the present study aimed to investigate the possible changes in the immunogenicity of MSCs during the differentiation to IPCs in a murine model of allogeneic transplantation. MATERIAL AND METHODS: Two mouse strains, C57BL/6 (H2Db) and BALB/c (H2Dd) were selected to establish an allogeneic cell transplantation model. Bone marrow MSCs were differentiated into IPCs and the expression of H2D, CD80, and Qa-2 molecules were evaluated via flowcytometry on MSCs and IPCs. The differentiated and undifferentiated MSCs were encountered to allogeneic splenocytes and the proliferation, CD44 activation marker, and cytokine release in the splenocytes were evaluated. RESULTS: IPCs exhibited increased expression of MHC-I and CD80 that elicited an allogenic response including the activation-induced proliferation of splenocytes, activation of CD4+ T cells, and IFNγ response. CONCLUSIONS: MSCs acquire immunogenicity after differentiation to functional IPCs, which might cause decreased efficacy in the case of allogeneic transplantation. Careful precautions might be critical for saving the IPCs against the detrimental allogeneic responses.

Electrospun silk nanofibers improve differentiation potential of human induced pluripotent stem cells to insulin producing cells.

With regard to lifestyle and diet, one of the problems that threaten mankind is diabetes. Given the lack of responsiveness to available drug therapies, the advances made in recent decades in tissue engineering and cell therapy have created a great deal of hope for the treatment of this disease. In this study, silk nanofibrous scaffold (3D) was fabricated by electrospinning and then its biocompatibility and non-toxicity by MTT assay. After that, scaffold supportive effects on human induced pluripotent stem cells (hiPSCs) differentiation to insulin producing cells (IPCs) was studied at the gene and protein levels. IPCs related genes and proteins were up regulated in electrospun silk group significantly greater than tissue culture plates group (2D). In addition, another part of the results demonstrated that differentiated cells on 2D and 3D groups have great functional properties including C-peptide and insulin secreting. It can be concluded that silk nanofibers has a great potential for use in pancreatic tissue engineering applications by support viability, growth and IPCs differentiation of iPSCs.

Wharton's Jelly Derived-Mesenchymal Stem Cells: Isolation and Characterization.

Wharton`s jelly-derived mesenchymal stem cells (WJ-MSCs), have a high proliferation valency and they do not produce teratogen or carcinogen after subsequent transplantation. They are known as regenerative medicine. Thus more research is needed on the isolation and characterization of mesenchymal stem cells. In this experimental study, we obtained Wharton's jelly tissues from mothers during normal vaginal delivery, after obtaining their informed consent. Mesenchymal stem cells were isolated from cultured Wharton`s jelly, cultured, and were then examined for their proliferation, immunophenotypes, and differentiation capacities. The immunophenotypes of WJ-MSCs were analyzed by flow cytometry. Differentiation was performed resulting in osteogenic, chondrogenic and adipogenic cells. WJ-MSCs formed a homogenous monolayer of adherent spindle-shaped cells. Our results showed the high capacity of the proliferation of WJ-MSCs. Immunophenotyping further confirmed the purity of the isolated cells; their surface antigen expression showed the phenotypical properties like those of WJ-MSCs. The expanded cells were positive for CD 90, CD105, and CD44; they were negative for CD34 and HLA-DR surface markers. The cells had the adipocytic, osteocytic and chondrogenic differentiation capacity. The isolation and characterization of WJ-MSCs with high purity had been conducted, and the results were obtained in a short span. The present study has revealed the feasibility of the culture medium with high glucose and 15% FBS in isolation and proliferation of WJ-MSCs. When Wharton`s jelly pieces were put in the dry bottom of the flask, very effective separation of the MSCs was achieved.

Differentiation of Wharton's Jelly Derived Mesenchymal Stem Cells into Insulin Producing Cells.

Background: Diabetes caused by insulin production disturbance is considered as the most common metabolic disorder all over the world. Diabetes may outbreak because of low insulin secretion by Islets of Langerhans ß-cells, insulin resistance or both of them. In this way, using stem cells, which have the capability to differentiate into pancreatic ß-cells, is one of novel methods in this field. MSCs are the most important candidates for cellular therapy. Materials and Methods: Insulin level was examined using ELIZA method. In order to examine the morphology of differentiated cells, they were stained by Dithizone. Insulin-producer cells are cells which turn into red as a result of staining. Specific gene involving insulin-producing cells was evaluated by Real Time-PCR method. Results: The ELISA results showed that the treated cells secreted more insulin than the control group. Moreover, we found differentiation of MSCs toward insulin-secreting cells. In order to evaluate insulin production in clusters on day 21 of differentiation, we used dithizone (DTZ) staining. PDX-1 gene was confirmed by RT- PCR analysis. Conclusion: In this study, we differentiated MSCs into insulin-producing cells in vitro. It is concluded that MSCs may be considered as an excellent candidate in ß-cell therapy in diabetes 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. In a case-control study, we investigated 30 threatened-abortion women with bleeding or spotting less than 20 weeks of pregnancy as compared to 30 normal pregnant women. uNK cells percentage was assessed by flow cytometry. Furthermore, we evaluated HLA-G1 and HLA-G5 isoforms expression by Real-Time PCR in these groups. The results of this study showed that threatened-abortion women had increased uNK cells and decreased T cells percentage in vaginal discharge in comparison with normal pregnant women (p = 0.01, p = 0.003, resp.). In addition, HLA-G1 isoform had lower expression in threatened-abortion women in comparison with control group (p = 0.0001). The increase of uNK cells level with the decrease of HLA-G expression in vaginal discharge of threatened-abortion pregnant women is an indicator of mother's immune dysregulation. It is concluded that HLA-G expression level with uNK cells percentage can be determined as a diagnostic marker for threatened-abortion women.

Path analysis of the risk of low birth weight for multipara.

BACKGROUND: LBW rate is one of the most important health indices in every society. It reveals mothers and their new-born infants' health. OBJECTIVES: Our aim, in the present paper, was to present a new statistical framework for analysis based on path analysis techniques. PATIENTS AND METHODS: A prospective study was conducted in two maternity wards, (privet & governmental hospital) in Sari, Iran. In this research a check-list containing 25 questions about mother's demographic information and her new-born infant was prepared. Every new born infant who was born weighing less than 2500 g was entered in our study and just next the newborn infant who was normal all of his/her information use to be taken too, (n = 190). Path analysis, an extension of the regression model, was used in this study. RESULTS: Obviously exactly half of the infants were LBW, and the remainder were normal. There were 97 boys and 93 girls. The percentage of IUGR among mothers who had preterm delivery was 19, while this percentage for mothers who had term delivery was 11.5 (P value = 0.167). LBW infants were 36.7% unexpected, while this percent for normal infants was 15.5 (P value < 0.001). Preterm delivery has a significant and direct effect on LBW (p value < 0.001), and its positive sign of path coefficient shows that if it occurs, the probability of LBW will increase, the second important was IUGR, the results showed unexpected pregnancy had direct effect on LBW but this wasn't significant (P value = 0.292). CONCLUSIONS: By preventing unnecessary termination of pregnancy and keeping fit, the chances of LBW can be reduced.

Epidemiologic and socioeconomic status of bladder cancer in Mazandaran Province, northern Iran.

BACKGROUND: Bladder cancer is one the most common malignancies of the genitourinary tract. The present study aimed to assess the epidemiology, of bladder cancer in Mazandaran, a large province in northern Iran as high-incidence cancer area, during a 2-year period. METHODS: The data for this study were obtained from the population-based cancer registry of the Vice-Chancellory for Health Affairs of Mazandaran University of Medical Sciences and Mazandaran hospitals between March 1, 2010 and March 1, 2011. Demographic data, including sex, age, residency and symptoms were investigated through careful review of medical records. Using a questionnaire protocol, several variables were assessed for these cases such as smoking, history of opium, vegetable consumption habits, and history of other cancers. RESULTS: A total of 112 cases were analyzed, 98 (87.5%) in men and 14 (12.5%) in women (mean age of 68.0 ± 14.6 years). Urban and rural residence were 60.7% and 39.3%. Tobacco and opium use were found in 45.5% and 21.4% of patients, respectively. Approximately 60% consumed vegetables an average of fewer than one time per day. Hematuria was the first symptom in these cases which were mainly diagnosed as having bladder cancer by ultrasonography. CONCLUSION: The results showed that bladder cancer tends to be found in the elderly and the male to female ratio is high. Macroscopic hematuria is a very important symptom for indicating probably urothelial tumor that should be followed up patients with transabdominal ultrasonography as a routine modality.