Interface between Resolvins and Efferocytosis in Health and Disease.

Acute inflammation resolution acts as a vital process for active host response, tissue support, and homeostasis maintenance, during which resolvin D (RvD) and E (RvE) as mediators derived from omega-3 polyunsaturated fatty acids display specific and stereoselective anti-inflammations like restricting neutrophil infiltration and pro-resolving activities. On the other side of the coin, potent macrophage-mediated apoptotic cell clearance, namely efferocytosis, is essential for successful inflammation resolution. Further studies mentioned a linkage between efferocytosis and resolvins. For instance, resolvin D1 (RvD1), which is endogenously formed from docosahexaenoic acid within the inflammation resolution, thereby provoking efferocytosis. There is still limited information regarding the mechanism of action of RvD1-related efferocytosis enhancement at the molecular level. The current review article was conducted to explore recent data on how the efferocytosis process and resolvins relate to each other during the inflammation resolution in illness and health. Understanding different aspects of this connection sheds light on new curative approaches for medical conditions caused by defective efferocytosis and disrupted inflammation resolution.

Whole exome sequencing reveals several novel variants in congenital disorders of glycosylation and glycogen storage diseases in seven patients from Iran.

BACKGROUND: Congenital disorder of glycosylation (CDG) and Glycogen storage diseases (GSDs) are inborn metabolic disorders caused by defects in some metabolic pathways. These disorders are a heterogeneous group of diseases caused by impaired O- as well as N-glycosylation pathways. CDG patients show a broad spectrum of clinical presentations; many GSD types (PGM1-CDG) have muscle involvement and hypoglycemia. METHODS: We applied WES for all seven patients presenting GSD and CDG symptoms. Then we analyzed the data using various tools to predict pathogenic variants in genes related to the patients' diseases. RESULTS: In the present study, we identified pathogenic variants in Iranian patients suffering from GSD and CDG, which can be helpful for patient management, and family counseling. We detected seven pathogenic variants using whole exome sequencing (WES) in known AGL (c.1998A>G, c.3635T>C, c.3682C>T), PGM1 (c.779G>A), DPM1 (c.742T>C), RFT1 (c.127A>G), and GAA (c.1314C>A) genes. CONCLUSION: The suspected clinical diagnosis of CDG and GSD patients was confirmed by identifying missense and or nonsense mutations in PGM1, DPM1, RFT1, GAA, and AGL genes by WES of all 7 cases. This study helps us understand the scenario of the disorder causes and consider the variants for quick disease diagnosis.

Whole-exome sequencing deciphers the genetic profile of visual impairments in patients from Southwest Iran.

Genetic ocular diseases are heterogeneous disorders. Recent advances have led to a paradigm shift in the discovery of eye disease-associated genetic variants from linkage and genome-wide association studies to next-generation sequencing-based genome studies. The aim of the current study was to investigate the spectrum of possible vision impairment-related variants in 66 Iranian patients. Whole-exome sequencing (WES) technology followed by bioinformatics analysis, Sanger validation, and co-segregation study were done to find eye disease-causing variants in the patients with vision impairments from Southwest Iran. WES revealed disease-causing variants in 82% of the enrolled cases. WES of understudied cohorts presented an effective strategy for determining pathogenic variants in heterogeneous eye diseases and demonstrated the distribution of causative genetic mutations in Iranian patients. The present data could provide the potential to accelerate genetic screening and a reference for treatment modalities for patients with different types of eye disorders from Southwest Iran.

Identification of Three Novel Mutations in the FANCA, FANCC, and ITGA2B Genes by Whole Exome Sequencing.

BACKGROUND: Various blood diseases are caused by mutations in the FANCA, FANCC, and ITGA2B genes. Exome sequencing is a suitable method for identifying single-gene disease and genetic heterogeneity complaints. METHODS: Among families who were referred to Narges Genetic and PND Laboratory in 2015-2017, five families with a history of blood diseases were analyzed using the whole exome sequencing (WES) method. RESULTS: We detected two novel mutations (c.190-2A>G and c.2840C>G) in the FANCA gene, c. 1429dupA mutation in the FANCC gene, and c.1392A>G mutation in the ITGA2B gene. The prediction of variant pathogenicity has been done using bioinformatics tools such as Mutation taster PhD-SNP and polyphen2 and were confirmed by Sanger sequencing. CONCLUSIONS: WES could be as a precise tool for identifying the pathologic variants in affected patient and heterozygous carriers among families. This highly successful technique will remain at the forefront of platelet and blood genomic research.

Wound Healing Activity of Extracts and Formulations of Aloe vera, Henna, Adiantum capillus-veneris, and Myrrh on Mouse Dermal Fibroblast Cells.

BACKGROUND: Among the most important factors in wound healing pathways are transforming growth factor beta1 and vascular endothelial growth factor. Fibroblasts are the main cell in all phases wound closure. In this study, the extracts of plant materials such as Adiantum capillus-veneris, Commiphora molmol, Aloe vera, and henna and one mixture of them were used to treatment of normal mouse skin fibroblasts. METHODS: Cytotoxic effects of each extract and their mixture were assessed on mouse skin fibroblasts cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. We performed migration assays to assess migration properties of mouse skin fibroblasts cells in response to the extracts. Changes in the gene expression of the Tgfß1 and Vegf-A genes were monitored by real-time polymerase chain reaction. RESULTS: A. capillus-veneris, C. molmol and henna extract improved the expression of Tgfß1 gene. All used extracts upregulated the expression of Vegf-A gene and promoted the migration of mouse fibroblast cells in vitro. CONCLUSIONS: The present study demonstrated that the mentioned herbal extracts might be effective in wound healing, through the improvement in the migration of fibroblast cells and regulating the gene expression of Tgfß1 and Vegf-A genes in fibroblast cells treated with extracts.

Effect of the herbal mixture composed of Aloe Vera, Henna, Adiantum capillus-veneris, and Myrrha on wound healing in streptozotocin-induced diabetic rats.

BACKGROUND: Wound healing is often impaired in diabetic animals and humans. Matrix metalloproteases act as pro-inflammatory agents in physiological wound healing pathways by stimulating cytokines including the interleukins, IL6, IL1A and IL1B, and the tumor necrosis factor and transforming growth factor beta1. Botanicals are traditionally used to assist healing of different types of wounds, because they produce fewer side effects. Our specific aim here was to develop a plant-based recipe supporting effective wound healing in diabetic animals. METHODS: Plant materials from Adiantum capillus-veneris, Commiphora molmol, Aloe Vera, and henna were collected for this study, and oven-dried at 60 °C. The dried leaves and resins were then crumbled into a powder and mixed in equal parts with Vaseline as a preservative. This mixture was used as an ointment on wounds induced in 60 diabetic and non-diabetic rats that were divided into 6 subgroups receiving agent or control treatments. Necrotic tissue surrounding the wound was periodically removed during wound healing. RNA was extracted from the healing region of the wound at days 7, 14 and 21 for cDNA synthesis to monitor changes in Tgfb1, Mmp3, Mmp9, Il6 and Tnf α expression using real-time PCR. RESULTS: The expression of the Mmp3, the Tnf α, and the Tgfb1 genes from wound tissue were significantly different (p < 0.05) between diabetic and non-diabetic (control) rats treated with the herbal mixture after 14 and 21 days. There was no significant difference (p > 0.05) of the Mmp9 gene expression in diabetic and non-diabetic rats treated only with Vaseline after 7, 14, and 21 days. But, the expression of the Mmp9 gene decreased significantly (p < 0.05) in diabetic rats after 14 days in comparison to non-diabetic rats, when the herbal mixture was added to Vaseline. CONCLUSIONS: Our study presents an herbal treatment that alters the gene expression signature at wounds induced in the rat model for type I diabetes in a manner consistent with accelerated healing, and demonstrates that this herbal treatment might be effective to treat wounds in diabetic patients.