Integrated Bioinformatic Analysis of Differentially Expressed Genes Associated with Wound Healing.

OBJECTIVE: Wound healing is a complex process involving the coordinated interaction of various genes and molecular
pathways. The study aimed to uncover novel therapeutic targets, biomarkers and candidate genes for drug development
to improve successful wound repair interventions.
Materials and Methods: This study is a network-meta analysis study. Nine wound healing microarray datasets obtained
from the Gene Expression Omnibus (GEO) database were used for this study. Differentially expressed genes (DEGs)
were described using the Limma package and shared genes were used as input for weighted gene co-expression
network analysis. The Gene Ontology analysis was performed using the EnrichR web server, and construction of a
protein-protein interaction (PPI) network was achieved by the STRING and Cytoscape.
Results: A total of 424 DEGs were determined. A co-expression network was constructed using 7692 shared genes
between nine data sets, resulting in the identification of seven modules. Among these modules, those with the top 20
genes of up and down-regulation were selected. The top down-regulated genes, including TJP1, SEC61A1, PLEK,
ATP5B, PDIA6, PIK3R1, SRGN, SDC2, and RBBP7, and the top up-regulated genes including RPS27A, EEF1A1,
HNRNPA1, CTNNB1, POLR2A, CFL1, CSNk1E, HSPD1, FN1, and AURKB, which can potentially serve as therapeutic
targets were identified. The KEGG pathway analysis found that the majority of the genes are enriched in the "Wnt
signaling pathway".
Conclusion: In our study of nine wound healing microarray datasets, we identified DEGs and co-expressed modules
using WGCNA. These genes are involved in important cellular processes such as transcription, translation, and posttranslational
modifications. We found nine down-regulated genes and ten up-regulated genes, which could serve as
potential therapeutic targets for further experimental validation. Targeting pathways related to protein synthesis and cell
adhesion and migration may enhance wound healing, but additional experimental validation is needed to confirm the
effectiveness and safety of targeted interventions.

A Review of Genes Involved in Wound Healing.

Background: Gene therapy holds immense potential in the field of wound healing. However, we still do not recognize this procedure well enough to give oversight effectively to improve healing processes. A wide range of information has been achieved from the database for gene expression profiling by clinical trials, So we performed this study to gain a better understanding of the mechanisms behind wound healing and how it could be utilized to develop new therapies and treatments. Methods: In this study, we have been focusing on wound-healing genes, conducting a thorough review to explore the various genes and pathways involved in this process. For this purpose, a total of 320 articles were collected. All experimental studies, systematic or narrative reviews, studies and clinical trials included in this paper were searched on PubMed, Medline, Embase, Science Direct, and Scopus databases in English using the following terms: Wound Healing, wound regeneration, Gene Transfer, and Gene Therapy were used to search the mentioned databases. Unfortunately, we didn't find a large sample cohort study on this topic. A total amount of 330 articles were collected based on the guidelines of the PRISMA method. Both inclusion and exclusion criteria were settled. Results: During the last decade, different models of gene delivery have been introduced, which include viral transfection and Non-viral techniques. In this regard, TIMP-2 protein and VEGF mutants such as VEGF165, CARP, and HIF-1 are the genes that accelerate the rate of tissue repair. Conclusion: The process of wound healing is mainly related to the change of expression of genes that have a role in the parts of inflammation and repair. In our study, some of the most suitable genes involved in the wound-healing process are mentioned.

Establishment and Preservation of Lymphoblastoid Cell Lines from Fresh and Frozen Whole Blood and Mononuclear Cells.

Although blood cells are interesting sources for genome investigations, one of the main problems in obtaining genomic DNA from blood is the restricted amount of DNA. This obstacle can be avoided by generating Epstein-Barr virus (EBV)-induced B cell lines. This study investigates the efficiency of four different methods to generate lymphoblastoid cell lines (LCLs). Blood samples (n = 120) were obtained from donors and categorized into four groups: fresh whole blood, frozen whole blood, fresh peripheral blood mononuclear cells (PBMCs), and frozen PBMCs. The samples were followed by EBV transformation to generate LCLs. Quality control and authentication of the cells were performed using multiplex PCR and short tandem repeat (STR) analyses. Finally, we assessed the success rate and amount of time to establish the cell lines in each group. The results showed that the cells were not contaminated nor were they misidentified or cross-contaminated with other cells. The success rate of LCLs generated from the whole blood groups was lower than the PBMC groups. The freezing procedures did not have any considerable effect on the establishment of lymphoblastoid cells. These established cells have been preserved in the human and animal cell bank of the Iranian Biological Resource Center (IBRC) and are available for researchers. Due to the management and transformation of a substantial number of blood samples, we recommend that researchers freeze PBMCs for further use with high efficiency and time-saving. We suggest that whole fresh blood should be directly transformed when the volume of the blood sample is less than 0.5 ml.

Effect of flavonoids rich extract of Capparis spinosa on inflammatory involved genes in amyloid-beta peptide injected rat model of Alzheimer's disease.

OBJECTIVES: Alzheimer's disease (AD) is one of the most common forms of neurodegenerative diseases. Despite vast ongoing researches focusing on the area, little is known about novel treatments. In this study, we aimed to survey the effects of Capparis spinosa (C. spinosa) extract on amyloid-beta peptide (Aß)-injected rat. METHODS: For this purpose, hydroalcoholic extracts of caper leaf and fruit were prepared. Total phenolic content, DPPH, and FRAP assay were accomplished to determine antioxidant activity of C. spinosa. HPLC analysis was conducted to measure rutin and quercetin content of selected parts of the plant. Higher levels of flavonoids were observed in leaves of the plant. Twelve male Wistar Aß-induced rats were randomly divided in four groups of (1) Aß-/DW+: Sham-operated group (2) Aß+/DW+: Aß-injected group (3) Aß+/RU+: Standard rutin treatment (4) Aß+/CS+: C. spinosa extract treatment. After 6 weeks of oral administration, real-time qPCR were conducted to determine APP, BACE-1, PSEN-1, and PSEN-2 genes expression in the hippocampus of rats. RESULTS: HPLC analysis showed high levels of rutin and quercetin in leaves of Capparis. Rutin was 16939.2 ± 0.01 and quercetin was 908.93 ± 0.01 µg/g fresh weight. In fruit, 1019.52 ± 0.01 rutin and 97.86 ± 0.01 µg/g FW quercetin were measured. Expression of BACE-1, APP, PSEN-1, and PSEN-2 genes in comparison with the control group showed significant down regulation. DISCUSSION: Results of the study demonstrated that C. spinosa has the potential to down regulate inflammation-involved genes in AD, due to its high levels of flavonoids and could be beneficial as a dietary complement in AD patients.

Congenital Malformations in Singleton Infants Conceived by Assisted Reproductive Technologies and Singleton Infants by Natural Conception in Tehran, Iran.

BACKGROUND: Multiple pregnancies occur more frequently in assisted reproductive technology (ART) compared to normal conception (NC). It is known that the risk of congenital malformations in a multiple pregnancy are higher than single pregnancy. The aim of this study is to compare congenital malformations in singleton infants conceived by ART to singleton infants conceived naturally. MATERIALS AND METHODS: In this historical cohort study, we performed a historical cohort study of major congenital malformations (MCM) in 820 singleton births from January 2012 to December 2014. The data for this analysis were derived from Tehran's ART linked data file. The risk of congenital malformations was compared in 164 ART infants and 656 NC infants. We performed multiple logistic regression analyses for the independent association of ART on each outcome. RESULTS: We found 40 infants with MCM 29 (4.4%) NC infants and 14 (8.3%) ART infants. In comparison with NC infants, ART infants had a significant 2-fold increased risk of MCM (P=0.046). After adjusting individually for maternal age, infant gender, prior stillbirth, mother's history of spontaneous abortion, and type of delivery, we did not find any difference in risk. In this study the majority (95.1%) of all infants were normal but 4.9% of infants had at least one MCM. We found a difference in risk of MCMs between in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). We excluded the possible role of genotype and other unknown factors in causing more malformations in ART infants. CONCLUSION: This study reported a higher risk of MCMs in ART singleton infants than in NC singleton infants. Congenital heart disease, developmental dysplasia of the hip (DDH), and urogenital malformations were the most reported major malformations in singleton ART infants according to organ and system classification.

Association of Two Polymorphisms in H2B.W Gene with Azoospermia and Severe Oligozoospermia in An Iranian Population.

BACKGROUND: During spermatogenesis, the H2B family, member W (H2B.W) gene, en- codes a testis specific histone that is co-localized with telomeric sequences and has the potential role to mediate the sperm-specific chromatin remodeling. Previously H2B.W genetic variants were reported to be involved in susceptibility to spermatogenesis im- pairment. In the present study, two single nucleotide polymorphisms (SNPs) in 5΄UTR and exon 1 of H2B.W gene were examined to investigate possible association of these polymorphisms with male infertility in Iranian population. MATERIALS AND METHODS: This case control study was conducted in Royan institute during four-year period (2010-2013). Genetic alteration of two SNPs loci, -9C>T and 368A>G, in H2B.W gene were indicated in 92 infertile men who were divided into two main groups includ- ing azoospermia (n=46) and sever oligozoospermia (n=46), while there was 60 fertile men as control group. Azoosperima was also divided into three sub-groups including sertoli cell only syndrome (SCOS, n=21), complete maturation arrest (CMA, n=17) and hypo spermatogenesis (n=8) according to testicular biopsy. For analysis, polymerase chain reaction-restriction frag- ment length polymorphism (PCR-RFLP) technique was applied. RESULTS: The frequency of allele -9T was significantly higher in CMA group than in patients with SCOS (P<0.05). The haplotype TA (corresponding to simultaneous occur- rence of -9T and 368A) compared with haplotype CA (corresponding to simultaneous occurrence of -9C and 368A) in patients suffering from CMA significantly increased, compared with patients had SCOS (P<0.05). However, statistical studies indicated that in general, the distribution frequencies of -9C>T and 368A>G had no significant difference between the infertile groups and control (P=0.859 and P=0.812, respectively). CONCLUSION: This investigation showed that SNP -9C>T might be contribute to CMA in azoo- spermic patients and SNP 368A>G had no correlation with male infertility in Iranian population.

Comparison of Congenital Abnormalities of Infants Conceived by Assisted Reproductive Techniques versus Infants with Natural Conception in Tehran.

BACKGROUND: In many countries, 1 to 3% of newborn infants are conceived by assisted reproductive techniques (ART). Despite the success of ART, there is concern about the risk of congenital malformations among these infants. We report our experience to determine whether use of ART is associated with an increase in major congenital malformations or adverse pregnancy outcomes. MATERIALS AND METHODS: Historical cohort study of major congenital malformations (MCM) was performed in 978 births from January 2008 to December 2010. The data for this analysis were derived from a Tehran's ART linked data file by simple sampling method. In our study, the risk of congenital malformations was compared in 326 ART infants and 652 naturally conceived (NC) infants. We also performed multiple logistic regression analyses to calculate the odds ratio (OR) and 95% confidence intervals (CI) for the independent association of ART on each outcome. RESULTS: We found 56 infants with major congenital malformations, these included 29 NC infants (4.4%) and 27 ART infants (8.3%). In comparison with NC infants, ART infants had a significant 1.94-fold increased risk of MCM.After adjustment for maternal age, infant's sex stillbirth, abortion and type of delivery, we found a relatively small difference in risk (OR=2.04). In this study the majority (94.3%) of all infants were normal but 5.7% of infants had at least one MCM. The prevalence rate for the intracytoplasmic sperm injection (ICSI) was 6.5% for the In vitro fertilisation (IVF) group was 15.9% or 2.73-fold higher than ICSI group (P=0.018). Also we ignore the possible role of genotype and other unknown factors in causing more malformations in ART infants. CONCLUSION: Other studies have shown a slightly increased risk of major congenital malformations in pregnancies resulting from ART. Likewise, this study reports a greater risk of MCMs in ART infants than in naturally conceived infants. We also found evidence of a difference in risk of MCMs between IVF and ICSI. Musculoskeletal and urogenital malformations were the most reported MCMs in ART infants according to organs and systems classification.