Diversity of HLA class I and class II alleles in Iran populations: Systematic review and Meta-Analaysis.

The human leukocyte antigen (HLA) system plays an essential role in the peptides antigen presentation and more regulation of immune responses. Regarding all HLA molecules' associations with various diseases and their clinical utilities in understanding drug reactions or prediction of transplantation outcome, there is a need for much more extensive HLA data generated from Asian countries. METHOD: A comprehensive search was conducted in electronic databases between 1990 and 2021 to identify relevant articles to HLA frequency in the normal Iranian population. Two independent reviewers screened and selected the eligible studies. After data extraction, the meta-analysis was performed using STATA version 14. The overall frequencies and their 95% confidence intervals (CIs) were obtained using the random-effects model. RESULTS: Among 1141 studies 78 were eligible for this study and the sample sizes varied from 14 to 15,600. The most frequent alleles of HLA class I were HLA-A*02 (22%; 95%CI: 20-24%; I2 = 88.63%), -B*35 (18%; 95%CI: 16-21%; I2 = 90.95%), -C*12 (18%; 95%CI: 13-22%; I2 = 89.51%). HLA-DQA1*01 (42%; 95%CI: 40-44%; I2 = 56.80%), -DQB1*03 (38%; 95%CI: 35-42%; I2 = 92.38%), and -DRB1*11 (24%; 95%CI: 22-26%; I2 = 90.72%) were the most frequent alleles of HLA class II in Iran. DISCUSSION: Our meta-analysis results point out that the comprehensive report of HLA allele frequency in the Iranian population could be helpful as reference data for planning and managing transplantation and immune disease treatment in Iran.

GDF15 induced apoptosis and cytotoxicity in A549 cells depends on TGFBR2 expression.

GDF15 plays a paradoxical role during carcinogenesis; it inhibits tumour growth in the early stages and promotes tumour cell proliferation in the late stages of cancer. Besides, GDF15 can induce apoptosis in some cancer cells including A549 but not in some others. Moreover, as a potential receptor for GDF15, TGFBR2 is inactivated during carcinogenesis in many types of cancers, and it is not present in cells with no GDF15 induced apoptosis. Thus, we tested whether GDF15 overexpression and/or TGFBR2 silencing can affect the GDF15 induced apoptosis in A549 cells. The full and mature forms of GDF15 were cloned and overexpressed in A549 cells. The TGFBR2 was silenced using specific siRNA and confirmed by real-time PCR. Results indicated that overexpression of full and mature forms of GDF15 as well as TGFBR2 knocked down reduced A549 cell viability in 24 and 48 hours. Flow cytometric analysis of annexin V/PI indicated induction of apoptosis in A549 cells by overexpression of GDF15 or silencing TGFBR2. Interestingly, the silencing of TGFBR2 inhibited the GDF15 induced cytotoxicity and apoptosis in A549 cells. Overexpression of GDF15 activated caspase-9 and caspase-3 and inhibited ERK1/2 and p38 phosphorylation in A549 cells. TGFBR2 knocked down inhibited GDF15 effects on caspases, ERK1/2, and p38MAPK activation. Our results indicated that the effect of GDF15 on apoptosis and activation of MAPK in A549 cells depends on TGFBR2 expression. These findings may point to mechanisms in which GDF15 exerts dual effect during carcinogenesis with regard to TGFBR2 expression. SIGNIFICANCE OF THE STUDY: GDF15 plays a tumour suppressor or promotor roles during carcinogenesis. The expression of GDF15 induced cytotoxicity, apoptosis, and inhibition of MAPK in A549 cells. All these effects were blocked by silencing TGFBR2 expression. These findings may point to mechanisms in which GDF15 exerts dual effect during carcinogenesis with regard to TGFBR2 expression.

Analysis of Risk Factors with Hospital Mortality in Pedestrian Injured Patients; A Dataset Analysis of a Level-I Trauma Center in Southern Iran.

OBJECTIVE: To determine the indicators predicting the hospital mortality in pedestrian injured patients admitted to a level I trauma center in Southern Iran. METHODS: This case control study was conducted in a Level-I trauma hospital in Shiraz. We selected all survived pedestrians who were admitted in the hospital with duration of admission more than 24 hours in one year from March 2016 to February 2017 as control group and compared with all non-survived pedestrian patients who expired in the hospital according to clinical from March 2012 to February 2017. Multiple logistic regression was performed to identify factors of hospital effect on pedestrian mortality and results expressed by Odds Ratios and their confidence intervals (CI) of 95%. RESULTS: A total of 424 survived pedestrian injured patients were compare to 117 non-survived one. Their mean of survived and non-survived patients were 43.79 ± 19.37 and 56.76 ± 18.55 years respectively of which 361 (66.7%) and 180 (33.3%) were men and women, respectively. We found that the gender does not have any relation with hospital mortality (p=0.275). Followed by, age is in relevance with mortality. Glasgow Coma Scale(GCS), Injury Severity Score (ISS), blood urea nitrogen (BUN), platelet (PLT), potassium (K) and hemoglobin (Hb) are significant factor which are associated with mortality. According to logistic analysis GCS ≤8 (p<0.001), low hemoglobin level <9 (p=0.030), BUN >24 (p<0.001), thrombocytopenia <150,000 (p<0.001), and hypokalemia <3.5 (p=0.01) were independently associated with hospital mortality. Among them, GCS≤8 was 72.237 times more likely to be associated with hospital mortality (OR =72.24, CI95% =23.19- 225.05). CONCLUSION: The results suggest that GCS score, ISS, hemoglobin level, platelet count, BUN and potassium level might be independent factors associated with hospital mortality in pedestrian injured patients.

Truncated forms of RUNX3 Unlike Full Length Protein Alter Cell Proliferation in a TGF-ß Context Dependent Manner.

The Runt related transcription factors (RUNX) are recognized as key players in suppressing or promoting tumor growth. RUNX3, a member of this family, is known as a tumor suppressor in many types of cancers, although such a paradigm was challenged by some researchers. The TGF-ß pathway governs major upstream signals to activate RUNX3. RUNX3 protein consists of several regions and domains. The Runt domain is a conserved DNA binding domain and is considered as the main part of RUNX proteins. Herein, we compared the effects of Runt domains and full-Runx3 in cell viability by designing two constructs of Runx3, including N-terminal region and Runt domain. We investigated the effect of full-Runx3, N-t, and RD on growth inhibition in AGS, MCF-7, A549, and HEK293 cell lines which are different in TGF-ß sensitivity, in the absence and presence of TGF-ß. The full length RUNX3 did not notably inhibit growth of these cell lines while, the N-t and RD truncates showed different trends in these cell lines. Cell proliferation in the TGF-ß impaired context cell lines (AGS and MCF-7) significantly decrease while in the A549 significantly increase. On the other hand, transfection of N-t and RD did not considerably affect the cell proliferation in the HEK293.Our results show that full-lenght RUNX3 did not affect the cell viability. Conversely, the N-t and RD constructs significantly changed cell proliferation. Therefore, therapeutic potentials for these truncated proteins are suggested in tumors with RUNX proteins dysfunction, even in the TGF-ß impair context.

Cell separation: Potentials and pitfalls.

Cell separation techniques play an indispensable part in numerous basic biological studies and even clinical settings. Although various cell isolation methods with diverse applications have been devised so far, not all of them have been able to gain widespread popularity among researchers and clinicians. There is not a single method known to be advantageous over all cell isolation techniques, and in fact, it is the researcher's aim in performing a study that determines the most suitable method. A perfect method for one study might not be necessarily a proper choice for another and likewise, expensive and complex isolation methods might not always be the best choices. There are several criteria such as cell purity, viability, activation status, and frequency that need to be given serious thought before selecting an isolation technique. Moreover, time and cost are two of the key elements that should be taken into consideration before implementing a project. Hence, here we provide a succinct description of six more popular cell separation methods with respect to their principles, advantages, and disadvantages as well as their most common applications. We further provide several key features of each technique so that it helps the researchers to take the first step toward opting for the best method that fits well into their projects.

EBV lymphoproliferative-associated disease and primary cardiac T-cell lymphoma in a STK4 deficient patient: A case report.

RATIONALE: Primary cardiac lymphoma (PLC) is an extremely uncommon malignancy. PCL is more common in secondary immunodeficient patients. In this report, we describe a unique case of PLC who had been diagnosed as a STK4 deficient patient. This case is the first Primary immunodeficiency (PID) patient developing PCL in the world. PATIENT CONCERNS: An eleven-year-old girl, a known case of PID, was referred to the pediatric cardiology department because of chest pain and dyspnea. Her CXR revealed cardiomegaly without mediastinal involvement and the echocardiography showed a mild pericardial effusion and cystic-shape echogenic masses. DIAGNOSES: After a period of missed follow up, she presented with respiratory distress following with syncope at the clinic because of a pressure effect of a large mass on the right ventricular outflow tract (RVOT) .An emergency operation was done for debulking of the tumors and resolving of RVOT obstruction. Biopsy and immunohistochemical staining was revealing "T-cell lymphoma", non-Hodgkin's type. INTERVENTIONS: Chemotherapy was done with cyclophosphamide, methotrexate, adriamycine, vincristine, hydrocortisone and allopurinol. OUTCOMES: The tumors shrank after chemotherapy initiation and she stayed stable for almost one month. Finally, she developed sever thrombocytopenia during her chemotherapy and died because of lung hemorrhage two months after her operation. LESSONS: Although PCL is very rare, it must be considered in the differential diagnosis of intracardiac mass or refractory pericardial effusions, especially in PIDs which are widely known for developing EBV-associated diseases such as lymphoma.