High inflammatory cytokines gene expression can be detected in workers with prolonged exposure to silver and silica nanoparticles in industries.

Occupational health must be strictly considered in industries particularly in nanoparticle factories where workers were exposed to different types of chemicals. We measured the serum levels of inflammatory cytokines in workers who developed skin lesions after exposure to silver and silica nanoparticles. Using a questionnaire in this cross-sectional study, we identified 110 workers in nanoparticle industries who were exposed to silver and silica nanoparticles. We also included 40 healthy subjects as controls from the administrative department of the same factories who were not exposed to nanoparticles. Peripheral blood samples used to measure the mRNA levels of inflammatory cytokines by qRT-PCR. In comparison with the control group, the workers who developed skin lesions had significantly higher levels of interleukin IL4, IL6, IL8, and TNF-α, particularly after two or three decades of exposure to silver and silica nanoparticles. Participants who were exposed to silver had higher levels of IL6 and IL8 compared with those who were exposed to silica. Necessary measures must be considered to protect workers in nanoparticle industries against the potential toxic effects of these compounds. Our network pharmacology study suggests corresponding biochemical pathways for these disorders.

Study of LncRNA BANCR Expression in Tumor Tissues and Adjacent Normal Tissues in Gastric Cancer Patients.

Background: Long non-coding RNAs (lncRNAs) have emerged as crucial regulators in various biological processes, including cancer development and progression. This study aimed to investigate the expression differences of the BRAF-activated non-coding RNA (BANCR) gene in GC tissues compared to adjacent normal tissues. The potential diagnostic significance of BANCR in GC was explored, with the aim of improving diagnostic and therapeutic approaches for this global health burden. Materials and Methods: Tissue samples from 100 gastric cancer (GC) patients were collected, and BANCR expression was analyzed using quantitative real-time PCR. Correlations between BANCR expression and clinicopathological features were assessed, and its biomarker potential was evaluated. Results: In individuals diagnosed with GC, the expression of BANCR was notably elevated in tumor tissues compared to adjacent normal tissues (P < 0.0001). However, the analysis of gene expression data did not demonstrate any statistically significant correlation between elevated BANCR expression and clinicopathological features. According to the ROC analysis, BANCR demonstrated an AUC of 0.6733 (P < 0.0001), with a sensitivity of 73% and a specificity of 45%. However, further evaluation is required to determine its potential as a biomarker (CI 95% = 0.5992 to 0.7473). Conclusions: The observed upregulation of BANCR in GC tissues implies its potential involvement as an oncogenic lncRNA in GC patients. Furthermore, BANCR may serve as a promising biomarker for identification and treatment of GC.

Drug repurposing based on differentially expressed genes suggests drug combinations with possible synergistic effects in treatment of lung adenocarcinoma.

Lung adenocarcinoma is one of the leading causes of cancer-related mortality globally. Various treatment approaches and drugs had little influence on overall survival; thus, new drugs and treatment strategies are needed. Drug repositioning (repurposing) seems a favorable approach considering that developing new drugs needs much more time and costs. We performed a meta-analysis on 6 microarray datasets to obtain the main genes with significantly altered expression in lung adenocarcinoma. Following that, we found major gene clusters and hub genes. We assessed their enrichment in biological pathways to get insight into the underlying biological process involved in lung adenocarcinoma pathogenesis. The L1000 database was explored for drug perturbations that might reverse the expression of differentially expressed genes in lung adenocarcinoma. We evaluated the potential drug combinations that interact the most with hub genes and hence have the most potential to reverse the disease process. A total of 2148 differentially expressed genes were identified. Six main gene clusters and 27 significant hub genes mainly involved in cell cycle regulation have been identified. By assessing the interaction between 3 drugs and hub genes and information gained from previous clinical investigations, we suggested the three possible repurposed drug combinations, Vorinostat - Dorsomorphin, PP-110 - Dorsomorphin, and Puromycin - Vorinostat with a high chance of success in clinical trials.

The Function of Autophagy in the Initiation, and Development of Breast Cancer

Autophagy is a significant catabolic procedure that increases in stressful conditions. This mechanism is mostly triggered after damage to the organelles, the presence of unnatural proteins, and nutrient recycling in reaction to these stresses. One of the key points in this article is that cleaning and preserving damaged organelles and accumulated molecules through autophagy in normal cells helps prevent cancer. Since dysfunction of autophagy is associated with various diseases, including cancer, it has a dual function in tumor suppression and expansion. It has newly become clear that the regulation of autophagy can be used for the treatment of breast cancer, which has a promising effect of increasing the efficiency of anticancer treatment in a tissue- and cell-type-specific manner by affecting the fundamental molecular mechanisms. Regulation of autophagy and its function in tumorigenesis is a vital part of modern anticancer techniques. This study discusses the current advances related to the mechanisms that describe essential modulators of autophagy involved in the metastasis of cancers and the development of new breast cancer treatments.

Rheumatoid arthritis and non-coding RNAs; how to trigger inflammation.

Rheumatoid arthritis (RA) is a systemic and chronic inflammatory disease categorized by continuous synovitis in the joints and systemic inflammatory responses that can cause lifelong disability. The major cause of RA is the dysregulation of the immune response. The development of RA disease includes multiplex association of several interleukins and cells, which leads to synovial cell growth, cartilage and bone damage. The primary stage of RA disease is related to the modification of both the innate and adaptive immune systems, which leads to the formation of autoantibodies. This process results in many damaged molecules and epitope spreading. Both the innate (e.g., dendritic cells, macrophages, and neutrophils) and acquired immune cells (e.g., T and B lymphocytes) will increase and continue the chronic inflammatory condition in the next stages of the RA disease. In recent years, non-coding RNAs have been proved as significant controllers of biological functions, especially immune cell expansion and reactions. Non-coding RNAs were primarily containing microRNA (miRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA). Various studies confirmed non-coding RNAs as hopeful markers for diagnosing and curing RA. This review will describe and cover existing knowledge about RA pathogenesis, which might be favorable for discovering possible ncRNA markers for RA.

An evaluation of gastric adenocarcinoma-associated CircRNAs based on microarray meta-analysis and ceRNA networks.

Gastric cancer is the fourth leading cause of cancer-related mortality and one of the most commonly diagnosed malignancies worldwide. Gastric adenocarcinoma (GAC) accounts for the majority of gastric cancer cases. Circular RNAs (circRNAs) have been shown to be associated with carcinogenesis and cancer progression. This research aims to investigate GAC-associated circRNAs and the underlying mechanisms of circRNA-miRNA-mRNA networks in the development and progression of GAC. Differentially expressed miRNAs and mRNAs (DEMs and DEGs) were identified in Gene Expression Omnibus (GEO) microarray datasets using the R package Limma. A microarray meta-analysis was performed to identify potential GAC-associated circRNAs with high statistical power, resulting in 13 up-regulated and 19 down-regulated circRNAs. CircRNA-miRNA-mRNA networks were constructed by combining predicted and experimentally validated databases and considering differentially expressed miRNAs and mRNAs. The constructed ceRNA networks revealed the potential regulatory effect of hsa_circ_0002019 and hsa_circ_0074736 on key survival-related genes. The expression levels of these two circRNAs were measured in plasma samples from GAC patients and healthy controls using SYBR Green-based real-time PCR. Axon guidance, cellular senescence, AGE-RAGE signaling pathway in diabetic complications, and AMPK signaling pathway were among the major significant (P-value <0.05) enriched pathways of "main mRNAs" in the constructed ceRNA networks. In conclusion, we identified strongly correlated circRNAs and their likely mechanisms of action in GAC, which may improve the knowledge of regulatory networks underlying GAC formation and contribute to developing better strategies for early diagnosis, prognosis, and treatment.

An Updated Review of Epigenetic-Related Mechanisms and their Contribution to Multiple Sclerosis Disease.

Multiple Sclerosis (MS) is a multifactorial, neurodegenerative, and inflammatory demyelination disease with incomplete remyelination in the CNS. It would be more informative to reveal the underlying molecular mechanisms of MS. Molecular mechanisms involving epigenetic changes play a pivotal role in this disease. Epigenetic changes impact gene expression without altering the underlying DNA sequence. The main epigenetic modifications that play a key role in the regulation of gene expression principally include DNA methylation, histone modifications, and microRNA- associated post-transcriptional gene silencing. In this review, we summarize the dynamics of epigenetic changes and their relation to environmental risk factors in MS pathogenesis. Studies suggest that epigenetic changes have a role in the development of MS and environmental risk factors, such as vitamin D, smoking, and Epstein-Barr virus infection seem to influence the development and susceptibility to MS. Investigating epigenetic and environmental factors can provide new opportunities for the molecular basis of the diseases, which shows complicated pathogenesis. Epigenetic research has the potential to complete our understanding of MS initiation and progression. Increased understanding of MS molecular pathways leads to new insights into potential MS therapies. However, there is a need for in vivo evaluation of the role of epigenetic factors in MS therapy. It would be more valuable to indicate the role of various epigenetic factors in MS.

Effects of Hair Follicle Stem Cells Coupled With Polycaprolactone Scaffold on Cutaneous Wound Healing in Diabetic Male Rats.

INTRODUCTION: Chronic wounds are debilitating complications of diabetes mellitus. The present study was conducted to investigate the effect of the hair follicle stem cells (HFSCs) by polycaprolactone scaffold on the healing of incisional cutaneous wounds on streptozotocin-induced diabetic male rats. METHODS: The wound model was obtained by a biopsy punch of the skin of the animals' back. The animals were randomly divided into five groups as follows: (1) Sham (nondiabetic, not treated), (2) Control (diabetic, not treated), (3) Scaffold (diabetic, treated with polycaprolactone nanofiber scaffold), (4) HFSCs (diabetic, treated with HFSCs), and (5) Scaffold + HFSCs (diabetic, treated with combination of Scaffold and HFSCs). The wounds were photographed in the course of the treatment and their healing rate was assessed. The samples were collected from the wound sites 7, 14, and 28 d after their development. Angiogenesis was surveyed by examining messenger RNA expression and the protein synthesis levels of vascular endothelial growth factor receptor 2 (VEGFR2) and platelet/endothelial cell adhesion molecule-1/cluster of differentiation 31. The histological changes were investigated using hematoxylin and eosin and Masson's trichrome staining. Furthermore, the wound breaking strength was measured on the 28th day by tensiometry. RESULTS: The application of the VEGFR2 as a substrate promotes the expression of CD31 in HFSCs and Scaffold + HFSCs groups compared to controls (P < 0.0001). HFSCs and scaffold also rescue the diabetes-induced dysfunction as assessed based on the parameters, such as viability, proliferation, colony formation, cellular adhesion, and chemotactic migration. HFSCs augment the levels of VEGFR2 and promote the restoration of the wound healing in diabetic groups. Furthermore, the maximum biomechanical stress significantly increased in the experimental diabetic groups (Scaffold: 1.38 ± 0.09, HFSCs: 2.13 ± 0.8, Scaffold + HFSCs: 2.38 ± 0.11) compared to the diabetes control group (1.16 ± 0.12). Using of HFSCs and scaffold on diabetic wounds leads to an accelerated wound closure, notably. CONCLUSIONS: Thus, the current data showed that HFSCs and scaffold form excellent biomaterial in the treatment of diabetic wounds.

Association of Aberrant Promoter Methylation Changes in the Suppressor of Cytokine Signaling 3 (SOCS3) Gene with Susceptibility to Crohn's Disease.

Background: Growing evidence supports that changes in the methylation state of Inflammatory Bowel Disease (IBD)-associated genes could significantly alter levels of gene expression, potentially contributing to disease onset and progression. We supposed that alterations in DNA methylation status at promoter region within the suppressor of cytokine signaling 3 (SOCS3) gene in intestinal tissues may be involved in the susceptibility to Crohn's Disease (CD). Methods: DNA methylation status in the promoter region of the human SOCS3 gene of intestinal tissues from 15 patients with CD and 15 age- and sex-matched healthy controls were profiled using the real-time Quantitative Multiplex Methylation Specific PCR (QM-MSP) assay. Results: Based on methylation assay data profiling, we found that patients with CD showed a higher degree of methylation of the SOCS3 gene promoter region than did the healthy controls (unmethylated DNA in CD vs. healthy controls; 0.00048±0.0011 vs. 0.07±0.142, p<0.000). Conclusion: The data presented here demonstrate that aberrant methylation of the CpG islands within promoter regions of SOCS3 gene in colonic mucosa of CD was associated with mucosal inflammatory status, providing insights into the involvement of methylation could contribute to the initiation of the inflammatory process and development of CD.

Epigenetic-related Effects of COVID-19 on Human Cells.

Epigenetics is related to the various pathways that show long-term impacts on the gene expression patterns without alterations in nucleotide sequences. Over the last decade, epigenetics advanced significantly in the science of biology, oncology, innate immunity as well as pathogens and infectious diseases. In the present paper, we aimed to review the relationships between COVID-19 and epigenetic alterations of the infected cells. Coronavirus is one of the known infectious diseases that causes respiratory infection, such as pneumonia and coughing, while in animals, it causes diarrhea and upper respiratory disorders. This virus could be transmitted human to human or human to an animal through droplets. It translocates via membrane ACE-2 exopeptidase into the host cells. In conclusion, hypomethylation of angiotensin II converting enzyme (ACE II) possibly upregulates its expression, enhancing the possibility of SARS-CoV-2 infection.

Identification of potentially functional circular RNAs hsa_circ_0070934 and hsa_circ_0004315 as prognostic factors of hepatocellular carcinoma by integrated bioinformatics analysis.

Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide, which has a high mortality rate and poor treatment outcomes with yet unknown molecular basis. It seems that gene expression plays a pivotal role in the pathogenesis of the disease. Circular RNAs (circRNAs) can interact with microRNAs (miRNAs) to regulate gene expression in various malignancies by acting as competitive endogenous RNAs (ceRNAs). However, the potential pathogenesis roles of the ceRNA network among circRNA/miRNA/mRNA in HCC are unclear. In this study, first, the HCC circRNA expression data were obtained from three Gene Expression Omnibus microarray datasets (GSE164803, GSE94508, GSE97332), and the differentially expressed circRNAs (DECs) were identified using R limma package. Also, the liver hepatocellular carcinoma (LIHC) miRNA and mRNA sequence data were retrieved from TCGA and differentially expressed miRNAs (DEMIs) and mRNAs (DEGs) were determined using the R DESeq2 package. Second, CSCD website was used to uncover the binding sites of miRNAs on DECs. The DECs' potential target miRNAs were revealed by conducting an intersection between predicted miRNAs from CSCD and downregulated DEMIs. Third, candidate genes were uncovered by intersecting targeted genes predicted by miRWalk and targetscan online tools with upregulated DEGs. The ceRNA network was then built using the Cytoscape software. The functional enrichment and the overall survival time of these potential targeted genes were analyzed, and a PPI network was constructed in the STRING database. Network visualization was performed by Cytoscape, and ten hub genes were detected using the CytoHubba plugin tool. Four DECs (hsa_circ_0000520, hsa_circ_0008616, hsa_circ_0070934, hsa_circ_0004315) were obtained and six miRNAs (hsa-miR-542-5p, hsa-miR-326, hsa-miR-511-5p, hsa-miR-195-5p, hsa-miR-214-3p, and hsa-miR-424-5p) which are regulated by the above DECs were identified. Then 543 overlapped genes regulated by six miRNAs mentioned above were predicted. Functional enrichment analysis showed that these genes are mostly associated with regulatory pathways in cancer. Ten hub genes (TTK, AURKB, KIF20A, KIF23, CEP55, CDC6, DTL, NCAPG, CENPF, PLK4) have been screened from the PPI network of the 204 survival-related genes. KIF20A, NCAPG, TTK, PLK4, and CDC6 were selected for the highest significance p-values. At the end, a circRNA-miRNA-mRNA regulatory axis was established for five final selected hub genes. This study implies the potential pathogenesis of the obtained network and proposes that the two DECs (has_circ_0070934 and has_circ_0004315) may be important prognostic markers for HCC.

Update of gene expression/methylation and MiRNA profiling in colorectal cancer; application in diagnosis, prognosis, and targeted therapy.

BACKGROUND: Colorectal cancer is one of the most deadliest malignancies worldwide. Due to the dearth of appropriate biomarkers, the diagnosis of this mortal disease is usually deferred, in its turn, culminating in the failure of prevention. By the same token, proper biomarkers are at play in determining the quality of prognosis. In other words, the survival rate is contingent upon the regulation of such biomarkers. MATERIALS AND METHODS: The information regarding expression (GSE41258, and GSE31905), methylation (GSE101764), and miRNA (dbDEMC) were downloaded. MEXPRESS and GEPIA confirmed the validated differentially expressed/methylated genes using TCGA data. Taking advantage of the correlation plots and receiver-operating-characteristic (ROC) curves, expression and methylation profiles were compared. The interactions between validated differentially expressed genes and differentially expressed miRNA were recognized and visualized by miRTarBase and Cytoscape, respectively. Then, the protein-protein interaction (PPI) network and hub genes were established via STRING and Cytohubba plugin. Utilizing R packages (DOSE, Enrichplot, and clusterProfiler) and DAVID database, the Functional Enrichment analysis and the detection of KEGG pathways were performed. Ultimately, in order to recognize the prognostic value of found biomarkers, they were evaluated through drawing survival plots for CRC patients. RESULTS: In this research, we found an expression profile (with 13 novel genes), a methylation profile (with two novel genes), and a miRNA profile with diagnostic value. Concerning diagnosis, the expression profile was evaluated more powerful in comparison with the methylation profile. Furthermore, a prognosis-related expression profile was detected. CONCLUSION: In addition to diagnostic- and prognostic-applicability, the discerned profiles can assist in targeted therapy and current therapeutic strategies.

Lactobacillus spp. derived biosurfactants effect on expression of genes involved in Proteus mirabilis biofilm formation.

Nosocomial infections (NIs) have been defined as infections ocuurring shortly after hospitalization or discharging from the hospital. It is associated with increased morbidities and mortalities. Proteus mirabilis considered as the hospital-acquired pathogen. The purpose of this study was to investigate the effect of Lactobacillus acidophilus-derived biosurfactant on P. mirabilis biofilm formation and flhDC/rsmA expression level (P. mirabilis standard strain ATCC 7002 and urinary infection isolated P. mirabilis strains). One of the potential strategies for the prevention of nosocomial infections is the use of probiotics. L. acidophilus was selected as a probiotic strain to produce biosurfactants. A biosurfactant reduces the adhesion of strains to microtiter plate and glass slide surfaces due to the reduction of surface tension. By using Real time PCR quantitation method we showed that biosurfactant significantly reduced rsmA expression whereas increased flhDC expression in P. mirabilis isolates. Several properties of P. mirabilis cells (biofilm formation, adhesion, and gene expression) were changed after L. acidophilus- derived biosurfactant treatment. In this study we showed that biosurfacant treatment can pave the way for a possible control of biofilm development. Based on our findings, we suggest that the prepared biosurfactant may interfere with adhesion of P. mirabilis to catheters and other devices.

An Updated Review of the Contribution of Noncoding RNAs to the Progression of Gastric Cancer Stem Cells: Molecular Mechanisms of Viability, Invasion, and Chemoresistance of Gastric Cancer Stem Cells.

Gastric cancer (GC) is the leading cause of death and cancer mortality in the world, with poor survival for cases with higher stages of GC. During the past decade, GC stem cells (GCSCs), a group of cancer cells, have been the focus of significant research on cancer. GCSCs have the capability of selfrenewal and are identified to participate in GC development, invasion, chemoresistance, and tumor relapse. Research projects have indicated the main activities of noncoding RNAs in cellular pathways. Micro (mi)RNAs and lncRNAs play important functions in the modulation of different cellular pathways in the post-transcriptional form through their dysregulated expression in several cancers, including GC. In this paper, we highlight the impact of dysregulated expression of micro- and lncRNAs and their downstream transcripts on GCSCs. Data collection on the progression of GCSCs may be beneficial for the introduction of new insights to the GC treatment.

Identification of let-7f and miR-338 as plasma-based biomarkers for sporadic amyotrophic lateral sclerosis using meta-analysis and empirical validation.

Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease that in most cases occurs sporadic (sALS). The disease is not curable, and its pathogenesis mechanisms are not well understood yet. Given the intricacy of underlying molecular interactions and heterogeneity of ALS, the discovery of molecules contributing to disease onset and progression will open a new avenue for advancement in early diagnosis and therapeutic intervention. Here we conducted a meta-analysis of 12 circulating miRNA profiling studies using the robust rank aggregation (RRA) method, followed by enrichment analysis and experimental verification. We identified miR-451a and let-7f-5p as meta-signature miRNAs whose targets are involved in critical pathogenic pathways underlying ALS, including 'FoxO signaling pathway', 'MAPK signaling pathway', and 'apoptosis'. A systematic review of 7 circulating gene profiling studies elucidated that 241 genes up-regulated in sALS circulation with concomitant being targets of the meta-signature miRNAs. Protein-protein interaction (PPI) network analysis of the candidate targets using MCODE algorithm revealed the main subcluster is involved in multiple cascades eventually leads apoptosis, including 'positive regulation of neuron apoptosis. Besides, we validated the meta-analysis results using RT-qPCR. Indeed, relative expression analysis verified let-7f-5p and miR-338-3p as significantly down-regulated and up-regulated biomarkers in the plasma of sALS patients, respectively. Receiver operating characteristic (ROC) analysis also highlighted the let-7f-5p and miR-338-3p potential as robustness plasma biomarkers for diagnosis and potential therapeutic targets of sALS disease.

An Updated Review of the Pre-Clinical Role of microRNAs and their Contribution to Colorectal Cancer.

Colorectal cancer (CRC) is one of the main causes of malignancy-related mortality worldwide. It was well-identified that microRNAs (miRNAs) decisively participate in cellular biological pathways; in a way that their deregulated expression causes CRC progression. miRNAs can control the translation and degradation of mRNAs by binding to various molecular targets involved in different biological processes, including growth, apoptosis, cell cycle, autophagy, angiogenesis, metastasis, etc. The functions of these dysregulated miRNAs may be either oncogenic or tumorsuppressive. Therefore, these miRNAs can be contributed to prognostic, diagnostic, and therapeutic approaches in CRC. In this study, we reviewed the tumor-suppressive and oncogenic functions of miRNAs in CRC and assessed their molecular activities in CRC development. However, further investigation for the involvement of dysregulated miRNAs in CRC progression is required.

HLA-DRB1 alleles as predisposing and resisting factor in women suffering from vulvovaginal candidiasis.

BACKGROUND: Vulvovaginal candidiasis (VVC) is a vaginal mucosal infection that usually affects women in their reproductive age. When the signs of VVC persist on a daily basis or last for a long time and repeat at least three times per year, the disease is considered chronic and recurrent. OBJECTIVE: The purpose of this study was to evaluate the frequency of HLA-DRB1 alleles in patients with recurrent vulvovaginal candidiasis (RVVC). STUDY DESIGN: 120 patients with RVVC and 136 age-matched healthy controls underwent low-resolution HLA-DRB typing performed using the polymerase chain reaction-sequence-specific primers (PCR-SSP) technique. RESULTS: In the present work, we studied different genes that encode HLA-DRB (HLA-DRB1 / HLA-DRB3 / HLA-DRB4 / HLA-DRB5) and showed that HLA-DRB1×14, found in 25% of the patients. In the present study, the significant frequency of HLA-DRB1×10 in the control group suggests a resistant role of this allele to RVVC infections CONCLUSIONS: In the HLA-DRB region, the DRB1×14 allele showed a higher frequency in the patients with RVVC than in the controls. Moreover, the higher frequency of DRB1×10 observed in the controls than in the patients with RVVC. These results demonstrate the HLA-DRB1 alleles are in relation with both susceptibility and immunity factors in RVVC infection and possible susceptible role of HLA-DRB1×14.

An updated review of the role of lncRNAs and their contribution in various molecular subtypes of breast cancer.

Introduction: Breast cancer (BC) is the most significant threat to women's life. To demonstrate its molecular mechanisms, which results in BC progression, it is crucial to develop approaches to enhance prognosis and survival in BC cases.Areas covered: In the current study, we aimed to highlight the updated data on the oncogenic and tumor suppressive roles of lncRNAs in the progression of various subtypes of BC by specifically putting importance on the functional characteristics, modulatory agents, therapeutic potential, future perspectives and challenges of lncRNAs in BC. We reviewed recent studies published between 2019 and 2020.Expert opinion: The latest investigations have demonstrated that the long non-coding RNAs (lncRNAs) participate in different BC molecular subtypes via different molecular mechanisms; however, the exact functional information of the lncRNAs has yet to be elucidated. The studied lncRNAs could be more applicable as therapeutic targets in BC treatment after pre-clinical and clinical studies.

Clinical features of children with atopic dermatitis according to filaggrin gene variants

Background: Filament aggregating protein (Filaggrin) is a skeletal cell component that provides a protective function for the epidermis. Mutations of the filaggrin gene (FLG) cause a loss of filaggrin protein. These mutations are seen in 50% of atopic dermatitis (AD). The aim of the study was to investigate the polymorphisms and mutations of the FLG in Iranian children with AD. Materials and methods: This project was a case-controlled study with 25 children diagnosed with AD as the case group and 25 healthy children as the control group. Demographic data, clinical manifestations, and filaggrin single nucleotide polymorphisms (SNPs) and mutations were recorded. Blood samples were collected for the immunoglobulin E (IgE) assay and complete blood count tests. Results: We found a significant association between the presence of polymorphism (rs66831674) and patients’ age, and polymorphism (rs41267154) and early onset of AD. We found no significant differences between the FLG polymorphisms with respect to the severity of AD, ethnicity, concurrent allergic diseases, eosinophilia, and IgE serum levels. Conclusion: Interestingly, FLG variants (rs66831674 and rs41267154) were associated with age and early onset of AD. However, additional studies are required to confirm these results on a large scale of Iranian population. Moreover, establishing a cohort prospective study is suggested to assess the progression of other atopic disorders based on FLG polymorphisms (AU)

Promising therapeutic approaches using CRISPR/Cas9 genome editing technology in the treatment of Duchenne muscular dystrophy.

Duchenne muscular dystrophy is an X-linked recessive hereditary monogenic disorder caused by inability to produce dystrophin protein. In most patients, the expression of dystrophin lost due to disrupting mutations in open reading frame. Despite the efforts in a large number of different therapeutic approaches to date, the treatments available for DMD remain mitigative and supportive to improve the symptoms of the disease, rather than to be curative. The advent of CRISPR/Cas9 technology has revolutionized genome editing scope and considered as pioneer in effective genomic engineering. Deletions or excisions of intragenic DNA by CRISPR as well as a similar strategy with exon skipping at the DNA level induced by antisense oligonucleotides, are new and promising approaches in correcting DMD gene, which restore the expression of a truncated but functional dystrophin protein. Also, CRISPR/Cas9 technology can be used to treat DMD by removing duplicated exons, precise correction of causative mutation by HDR-based pathway and inducing the expression of compensatory proteins such as utrophin. In this study, we briefly explained the molecular genetics of DMD and a historical overview of DMD gene therapy. We in particular focused on CRISPR/Cas9-mediated therapeutic approaches that used to treat DMD.