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Background: Accomplishments in stem cell science and tissue engineering have resulted in a remarkable revolution in the context of future medicine. However, a general insight over the progress of stem cell research in Iran is still lacking. A better understanding of current needs in this field is required to design a better national roadmap. Methods: In this study, we defined the geographical regions based on the significance of their contribution to stem cell research; then, using the Scopus database, we retrieved reports from Iran and other countries concerning stem cell science and regenerative medicine published from 1994 until the end of 2016. Results: A significant number of citations belong to North America (6 554 029 citations equal to 49% of the total citations) and Europe (4 425 465 citations equal to 33% of the total citations) and the rest of citations were related to Asia (2 423 352 citations equal to 18% of the total citations). East Asian (2 168 472 citations equal to 76% of the total citations related to Asia) documents were cited more than those from the Middle East (ME) (494 141 citations equal to 17% of the total citations related to Asia) and North and Central Asia (196 382 citations equal to 7% of the total citations related to Asia). Iran as a country in the ME attracted 17% of the total citations related to the Asian countries winning the second position in this regard. The overview of total number of citations showed a sharp increase and upward trend in citation numbers for all the Iranian institutes from 2007 that resulted in the expansion of stem cell science in all major cities of Iran such as Shiraz (8%), Mashhad (5%), Isfahan (5%) and Ahvaz (5%). H-index of Tehran University of Medical Science, which has the highest total citations and document numbers, is the highest among all Iranian research institutes. Citation per paper of Royan Institute (RI) is the highest among the top 10 Iranian institutes, by 13 citations per paper. Conclusion: Stem cell research in Iran is rapidly developing. Since 2007, the number of published documents in major research institutes increased; thus, there is necessity for analysis of the status of publications in this field and choosing a better direction based on needs. Furthermore, it is necessary to expand and organize international collaborations to enrich our research and benefit from different team experiences. [ABSTRACT FROM AUTHOR]

Abstract: Background: Most two‐ dimensional in vitro models for studying host‐ H. pylori interactions rely on tumor‐derived cell lines, which harbor malignant alterations. The recent development of human gastric organoids has overcome this limitation and provides a highly sophisticated, yet costly, short‐term model for H. pylori infection, with restricted use in low‐budget centers. Method: Tissue specimens from upper, middle, and lower stomachs of H. pylori‐negative volunteers were collectively dispersed and cultured on mouse embryonic fibroblast (MEF) or collagen‐coated plates. Gastric primary cells (GPCs) were evaluated by light microscopy, immunostaining, qRT‐PCR and ELISA analysis of cellular secretions, before and after H. pylori infection. Results: The formation and long‐term (up to 1 year) maintenance of GPCs was highly dependent on adherent inactivated MEF cells, cultured in enriched media. These cells were multipassageable and able to undergo stable freezer storage and subsequent revival. The cellular composition of GPCs included the combination of cytokeratin 18 (CK18) and E‐cadherin (E‐cad)‐positive epithelial cells, MUC5AC‐positive gastric cells, and leucine‐rich repeat containing G protein‐coupled receptor 5 (LGR5)‐positive progenitor cells. These cells produced significant amounts of gastric pepsinogens I and II. GPCs also allowed for extended (up to 96 hours) H. pylori infection, during which they underwent morphological alterations (cellular vacuolation and elongation) and hyperproduction of gastric pepsinogens and inflammatory cytokines (IL‐8 and TNF‐α). Conclusion: We, hereby, present a simple, consistent, and cost‐efficient gastric cell culture system, which provides a suitable model for extended in vitro infection of H. pylori. This platform can be employed for a variety of gastric‐related research. [ABSTRACT FROM AUTHOR]

Gastric cancer is a silent killer, claiming more than seven hundred thousand lives every year. This heavy burden creates an irrefutable need for accurate, noninvasive methods of population screening and early detection as well as disease monitoring and management. Gastric cancer is a multi-factorial disease with an uneven geographic distribution, mostly affecting the developing countries and Southeast Asia. The multi-dimensional roles of microRNAs in gene regulation and tumorigenesis have prompted investigators to explore their potentials in diagnosis and treatment of various cancers, including gastric cancer. In this respect, miR-21 has attracted much attention as well as generating some controversies. Here, we aim to describe, in a chronological order, the numerous studies which have explored 1) the interactions of this oncomir with Helicobacter pylori infection, as a class I gastric carcinogen, 2) its potential mechanisms of oncogenicity, by various induction/inhibition assays, and 3) its application as a diagnostic/prognostic invasive (tissue) and non-invasive (circulating) biomarker. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to introduce novel techniques for identifying the genes associated with developing chronic obstructive pulmonary disease (COPD) and to prioritize COPD candidate genes using regression methods. Materials and Methods: This is a secondary analysis of the data from an experimental study. We used penalized logistic regressions with three different types of penalties included least absolute shrinkage and selection operator (LASSO), minimax concave penalty (MCP), and smoothly clipped absolute deviation (SCAD). The models were trained using genome-wide expression profiling to define gene networks relevant to the COPD stages. A 10-fold cross-validation scheme was used to evaluate the performance of the methods. In addition, we validate our results by the external validity approach. We reported the sensitivity, specificity, and area under curve (AUC) of the models. Results: There were 21, 22, and 18 significantly associated genes for LASSO, SCAD, and MCP models, respectively. The most statistically conservative method (detecting less significant features) was MCP detected 18 genes that were all detected by the other two approaches. The most appropriate approach was a SCAD penalized logistic regression (AUC= 96.26, sensitivity= 94.2, specificity= 86.96). In this study, we have a common panel of 18 genes in all three models that show a significant positive and negative correlation with COPD, in which RNF130, STX6, PLCB1, CACNA1G, LARP4B, LOC100507634, SLC38A2, and STIM2 showed the odds ratio (OR) more than 1. However, there was a slight difference between penalized methods. Conclusion: Regularization solves the serious dimensionality problem in using this kind of regression. More exploration of how these genes affect the outcome and mechanism is possible more quickly in this manner. The regression-based approaches we present could apply to overcoming this issue. [ABSTRACT FROM AUTHOR]

Objective: Liver transplantation is the gold standard approach for decompensated liver cirrhosis. In recent years, stem cell therapy has raised hopes that adjusting some clinical and laboratory parameters could lead to successful treatments for this disease. Cirrhotic patients may have multiple systemic abnormalities in peripheral blood and irregular cell populations in bone marrow (BM). Correcting these abnormalities before BM aspiration may improve the effectiveness of cell-based therapy of liver cirrhosis. Materials and Methods: In this controlled clinical trial study, 20 patients with decompensated liver cirrhosis were enrolled. Patients were randomly assigned to control and experimental groups. Blood samples were obtained to measure vitamin B12, folate, serum iron, total iron bonding capacity (TIBC) and ferritin before any intervention. Furthermore, the iron storage and fibrosis level in BM biopsies, as well as the percentage of different cell populations, were evaluated. Prior to cell isolation for transplantation, we performed palliative supplement therapy followed by a correction of nutritional deficiencies. Mononuclear cells (MNCs) were then isolated from BM aspirates and transfused through peripheral vein in patients in the experimental group. The model of end-stage liver disease (MELD) score, The international normalized ratio (INR), serum albumin and bilirubin levels were assessed at 0 (baseline), 3 and 6 months after cell transplantation. Results: The MELD score (P=0.0001), INR (P=0.012), bilirubin (P<0.0001) and total albumin (P<0.0001) levels improved significantly in the experimental group after cell transplantation compared to the baseline and control groups. Moreover, the increase in serum albumin levels of patients in the experimental group was statistically significant 6 months after transplantation. Conclusion: We have successfully improved the conditions of preparing -BM-derived stem cells for transplantation. Although these cells are relatively safe and have been shown to improve some clinical signs and symptoms temporarily, there need to be more basic studies regarding the preparation steps for effective clinical use (Registration number: IRCT2014091919217N1). [ABSTRACT FROM AUTHOR]

Background: Variations in mitochondrial DNA copy number (mtDNA-CN) of peripheral blood leukocytes (PBLs), as a potential biomarker for gastric cancer (GC) screening has currently been subject to controversy. Herein, we have assessed its efficiency in GC screening, in parallel and in combination with serum pepsinogen (sPG) I/II ratio, as an established indicator of gastric atrophy., Methods: The study population included GC (n = 53) and non-GC (n = 207) dyspeptic patients. The non-GC group was histologically categorized into CG (n = 104) and NM (n = 103) subgroups. The MtDNA-CN of PBLs was measured by quantitative real-time PCR. The sPG I and II levels and anti-H. pylori serum IgG were measured by ELISA., Results: The mtDNA-CN was found significantly higher in GC vs. non-GC (OR = 3.0; 95% CI = 1.4, 6.4) subjects. Conversely, GC patients had significantly lower sPG I/II ratio than the non-GC (OR = 3.2; CI = 1.4, 7.2) subjects. The combination of these two biomarkers yielded a dramatic amplification of the odds of GC risk in double-positive (high mtDNA-CN-low sPGI/II) subjects, in reference to double-negatives (low mtDNA-CN-high sPGI/II), when assessed against non-GC (OR = 27.1; CI = 5.0, 147.3), CG (OR = 13.1; CI = 2.4, 72.6), or NM (OR = 49.5; CI = 7.9, 311.6) groups., Conclusion: The combination of these two biomarkers, namely mtDNA-CN in PBLs and serum PG I/II ratio, drastically enhanced the efficiency of GC risk assessment, which calls for further validations.

Gastric cancer is a silent killer, claiming more than seven hundred thousand lives every year. This heavy burden creates an irrefutable need for accurate, noninvasive methods of population screening and early detection as well as disease monitoring and management. Gastric cancer is a multi-factorial disease with an uneven geographic distribution, mostly affecting the developing countries and Southeast Asia. The multi-dimensional roles of microRNAs in gene regulation and tumorigenesis have prompted investigators to explore their potentials in diagnosis and treatment of various cancers, including gastric cancer.  In this respect, miR-21 has attracted much attention as well as generating some controversies. Here, we aim to describe, in a chronological order, the numerous studies which have explored 1) the interactions of this oncomir with Helicobacter pylori infection, as a class I gastric carcinogen, 2) its potential mechanisms of oncogenicity, by various induction/inhibition assays, and 3) its application as a diagnostic/prognostic invasive (tissue) and non-invasive (circulating) biomarker.

Background: Cytokine gene single nucleotide polymorphisms (SNPs) are widely used to study susceptibility to complex diseases and as a tool for anthropological studies., Materials and Methods: To investigate cytokine SNPs in an Iranian multi-ethnic population, we have investigated 10 interleukin (IL) SNPs (IL-1β (C-511T, T-31C), IL-2 (G-384T), IL-4 (C-590T), IL-6 (G-174C), IL-8 (T-251A), IL-10 (G-1082A, C-819T, C-592A) and tumor necrosis factor-alpha (TNF-α) (G-308A) in 415 Iranian subjects comprising of 6 different ethnicities. Allelic and genotypic frequencies as well as Hardy-Weinberg equilibrium (HWE) were calculated by PyPop software. Population genetic indices including observed heterozygosity (Ho), expected heterozygosity (He), fixation index (FIS), the effective number of alleles (N e) and polymorphism information content (PIC) were derived using Popgene 32 software. Multidimensional scaling (MDS) was constructed using Reynold's genetic distance obtained from the frequencies of cytokine gene polymorphism., Results: Genotypic distributions were consistent with the HWE assumptions, except for 3 loci (IL-4-590, IL-8-251 and IL-10-819) in Fars and 4 loci (IL-4-590, IL-6-174, IL-10-1082 and TNF-α-308) in Turks. Pairwise assessment of allelic frequencies, detected differences at the IL-4-590 locus in Gilakis versus Kurds (P = 0.028) and Lurs (P = 0.022). Mazanis and Gilakis displayed the highest (Ho= 0.50 ± 0.24) and lowest (Ho= 0.34 ± 0.16) mean observed heterozygosity, respectively., Conclusions: MDS analysis of our study population, in comparison with others, revealed that Iranian ethnicities except Kurds and Mazanis were tightly located within a single cluster with closest genetic affinity to Europeans.