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Amyotrophic lateral sclerosis (ALS) is a rare disorder that affects both upper and lower motor neurons. Mutations in Alsin Rho Guanine Nucleotide Exchange Factor (ALS2) correlates with three similar but distinctive syndromes, including the juvenile form of ALS. An Iranian Kurdish family was involved in this study and all members were evaluated with relevant clinical guidelines. Whole exome sequencing and sanger sequencing were applied to all family members to undermine the possible genetic factors. A substitution c. 2110 C>T (p. Arg704X) identified in the ALS2 gene. Bioinformatics analysis indicated the mutation is located in the well-conserved and functional domain of the protein. This study recognized a novel mutation in the ALS2 gene in a proband with the juvenile form of ALS. To our knowledge, this is the first identified ALS2 mutation among the Iranian population.

Since the authors are not responding to the editor’s requests to fulfill the editorial requirement, therefore, the article has been withdrawn., Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused., The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policiesmain. php, Bentham Science Disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net)

Purpose: Primary congenital glaucoma (PCG) (OMIM#231,300) can be caused by pathogenic sequence variations in CYP1B1, LTBP2, MYOC and PXDN genes. The purpose of this study was to investigate mutations in the CYP1B1 gene in families affected with primary congenital glaucoma (PCG) using linkage analysis and Sanger sequencing., Methods: A total number of four families with nine affected PCG patients during six months were included in this study. The mutations were identified by homozygosity mapping to find the linked loci and then direct sequencing of all coding exons, the exon-intron boundaries and the 5' untranslated region of CYP1B1 using genomic DNA obtained from affected family members and their parents. Moreover, bioinformatic tools were applied to study mutation effect on protein structure and function., Results: A total of four mutations were identified, and three of these were novel. Two were missense mutations: One was truncating mutation, and the other was an in-frame deletion. Mutations in CYP1B1 could fully explain the PCG phenotype in all of the patients. Also, the bioinformatic study of the mutations showed the structure of the protein is affected, and it is well conserved among similar species., Conclusion: In this study, we identified 4 CYP1B1 mutations, 3 of which were novel. In silico analysis of identified mutations confirmed their molecular pathogenicity. A similar analysis will help understand the biological role of CYP1B1 and the effect of mutations on the regulatory and enzymatic functions of CYP1B1 that result in PCG., Clinical Trials Registration: Not relevant., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Most commonly recognized as a catabolic pathway, autophagy is a perplexing mechanism through which a living cell can free itself of excess cytoplasmic components, i.e., organelles, by means of certain membranous vesicles or lysosomes filled with degrading enzymes. Upon exposure to external insult or internal stimuli, the cell might opt to activate such a pathway, through which it can gain control over the maintenance of intracellular components and thus sustain homeostasis by intercepting the formation of unnecessary structures or eliminating the already present dysfunctional or inutile organelles. Despite such appropriateness, autophagy might also be considered a frailty for the cell, as it has been said to have a rather complicated role in tumorigenesis. A merit in the early stages of tumor formation, autophagy appears to be salutary because of its tumor-suppressing effects. In fact, several investigations on tumorigenesis have reported diminished levels of autophagic activity in tumor cells, which might result in transition to malignancy. On the contrary, autophagy has been suggested to be a seemingly favorable mechanism to progressed malignancies, as it contributes to survival of such cells. Based on the recent literature, this mechanism might also be activated upon the entry of engineered nanomaterials inside a cell, supposedly protecting the host from foreign materials. Accordingly, there is a good chance that therapeutic interventions for modulating autophagy in malignant cells using nanoparticles may sensitize cancerous cells to certain treatment modalities, e.g., radiotherapy. In this review, we will discuss the signaling pathways involved in autophagy and the significance of the mechanism itself in apoptosis and tumorigenesis while shedding light on possible alterations in autophagy through engineered nanomaterials and their potential therapeutic applications in cancer. SIGNIFICANCE STATEMENT: Autophagy has been said to have a complicated role in tumorigenesis. In the early stages of tumor formation, autophagy appears to be salutary because of its tumor-suppressing effects. On the contrary, autophagy has been suggested to be a favorable mechanism to progressed malignancies. This mechanism might be affected upon the entry of nanomaterials inside a cell. Accordingly, therapeutic interventions for modulating autophagy using nanoparticles may sensitize cancerous cells to certain therapies., (Copyright © 2021 by The American Society for Pharmacology and Experimental Therapeutics.)

The term 'MicroRNA' (miRNA) refers to a class of small endogenous non-coding RNAs (ncRNAs) regenerated from hairpin transcripts. Recent studies reveal miRNAs' regulatory involvement in essential biological processes through translational repression or mRNA degradation. Recently, there is a growing body of literature focusing on the importance of miRNAs and their functions. In this respect, several databases have been developed to manage the dispersed data produced. Therefore, it is necessary to know the parameters and characteristics of each database to benefit their data. Besides, selecting the correct database is of great importance to scientists who do not have enough experience in this field. A comprehensive classification along with an explanation of the information contained in each database leads to facilitating access to these resources. In this regard, we have classified relevant databases into several categories, including miRNA sequencing and annotation, validated/predicted miRNA targets, disease-related miRNA, SNP in miRNA sequence or target site, miRNA-related pathways, or gene ontology, and mRNA-miRNA interactions. Hence, this review introduces available miRNA databases and presents a convenient overview to inform researchers of different backgrounds to find suitable miRNA-related bioinformatics web tools and relevant information rapidly., (Copyright © 2021. Published by Elsevier Ltd.)

Purpose: Bardet-Biedl syndrome (BBS: OMIM 209,900) is a rare ciliopathic human genetic disorder that affects many parts of the body systems. BBS is a genetically heterogeneous disorder with a wide spectrum of clinical manifestations which makes its diagnosis and management more challenging. RetNet reports 18 genes that cause BBS and each of genes has had several known mutations. Genetic studies suggesting that serologically defined colon cancer antigen 8 (SDCCAG8) gene mutations are a major cause of BBS., Materials and Methods: In this section, we investigated the consanguineous Iranian family members with BBS. Whole-exome sequencing and Sanger sequencing, were performed to screen and confirm the suspicious pathogenic mutations. The identified mutation was investigated using bioinformatics tools to predict the effect of the mutation on protein structure., Results: Sequential analysis identified a novel splice site mutation c.1221 + 2 T > A in the SDCCAG8 gene in BBS patients. Structure-based approaches have predicted significant structural alterations in SDCCAG8 protein., Conclusions: This study was conducted to show the aberrant alternative splicing as one of the single splicing mutations identified can cause BBS by affecting the function of SDCCAG8 protein.

DNA damage usually happens in all cell types, which may originate from endogenous sources (i.e., DNA replication errors) or be emanated from radiations or chemicals. These damages range from changes in few nucleotides to significant structural abnormalities on chromosomes and, if not repaired, could disturb the cellular homeostasis or cause cell death. As the most significant response to DNA damage, DNA repair provides biological pathways by which DNA damages are corrected and returned into their natural circumstance. However, an aberration in the DNA repair mechanisms may result in genomic and chromosomal instability and the accumulation of mutations. The activation of oncogenes and/or inactivation of tumor suppressor genes is a serious consequence of genomic and chromosomal instability and may bring the cells into a cancerous phenotype. Therefore, genomic and chromosomal instability is usually considered a crucial factor in carcinogenesis and an important hallmark of various human malignancies. In the present study, we review our current understanding of the most updated mechanisms underlying genomic instability in cancer and discuss the potential promises of these mechanisms in finding new targets for the treatment of cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Gastric cancer (GC) is a major health issue in the Western world. Current clinical imperatives for this disease include the identification of more effective biomarkers to detect GC at early stages and enhance the prevention and treatment of metastatic and chemoresistant GC. The advent of non-coding RNAs (ncRNAs), particularly microRNAs (miRNAs) and long-non coding RNAs (lncRNAs), has led to a better understanding of the mechanisms by which GC cells acquire features of therapy resistance. ncRNAs play critical roles in normal physiology, but their dysregulation has been detected in a variety of cancers, including GC. A subset of ncRNAs is GC-specific, implying their potential application as biomarkers and/or therapeutic targets. Hence, evaluating the specific functions of ncRNAs will help to expand novel treatment options for GC., Conclusions: In this review, we summarize some of the well-known ncRNAs that play a role in the development and progression of GC. We also review the application of such ncRNAs in clinical diagnostics and trials as potential biomarkers. Obviously, a deeper understanding of the biology and function of ncRNAs underlying chemoresistance can broaden horizons toward the development of personalized therapy against GC.

Pancreatic cancer is the most lethal malignancy of the gastrointestinal tract. Due to its propensity for early local and distant spread, affected patients possess extremely poor prognosis. Currently applied treatments are not effective enough to eradicate all cancer cells, and minimize their migration. Besides, these treatments are associated with adverse effects on normal cells and organs. These therapies are not able to increase the overall survival rate of patients; hence, finding novel adjuvants or alternatives is so essential. Up to now, medicinal herbs were utilized for therapeutic goals. Herbal-based medicine, as traditional biotherapeutics, were employed for cancer treatment. Of them, apigenin, as a bioactive flavonoid that possesses numerous biological properties (e.g., anti-inflammatory and anti-oxidant effects), has shown substantial anticancer activity. It seems that apigenin is capable of suppressing the proliferation of cancer cells via the induction of cell cycle arrest and apoptosis. Besides, apigenin inhibits metastasis via down-regulation of matrix metalloproteinases and the Akt signaling pathway. In pancreatic cancer cells, apigenin sensitizes cells in chemotherapy, and affects molecular pathways such as the hypoxia inducible factor (HIF), vascular endothelial growth factor (VEGF), and glucose transporter-1 (GLUT-1). Herein, the biotherapeutic activity of apigenin and its mechanisms toward cancer cells are presented in the current review to shed some light on anti-tumor activity of apigenin in different cancers, with an emphasis on pancreatic cancer., (Copyright © 2020 Ashrafizadeh, Bakhoda, Bahmanpour, Ilkhani, Zarrabi, Makvandi, Khan, Mazaheri, Darvish and Mirzaei.)

Although 70 % of the genome is transcribed to RNA in humans, only ∼2% of these transcripts are translated into proteins. The rest of the transcripts are defined as noncoding RNAs, including Long noncoding RNAs (LncRNAs) and MicroRNAs (miRNAs) that mostly function post-transcriptionally to regulate the gene expression. The outbreak of a novel coronavirus (SARS-CoV) has caused a major public health concern across the globe. The SARS-CoV is the seventh coronavirus that is known to cause human disease. There are currently no promising antiviral drugs with proven efficacy nor are there vaccines for its prevention. As of August 10, 2020, SARS-CoV has been infected more than 13 million cases in more than 213 countries, with an estimated mortality rate of ∼3 %. Thus, it is of utmost important priority to develop novel therapies for COVID-19. It is not fully investigated whether noncoding RNAs regulate signaling pathways that SARS-CoV involved in. Hence, computational analysis of the noncoding RNA interactions and determining importance of key regulatory noncoding RNAs in antiviral defense mechanisms will likely be helpful in developing new drugs to attack SARS-CoV infection. To elucidate this, we utilized bioinformatic approaches to find the interaction network of SARS-CoV/human proteins, miRNAs, and lncRNAs. We found TGF-beta signaling pathway as one of the potential interactive pathways. Furthermore, potential miRNAs/lncRNAs networks that the virus might engage during infection in human host cells have been shown. Altogether, TGF-beta signaling pathway as well as hub miRNAs, and LncRNAs involve during SARS-CoV pathogenesis can be considered as potential therapeutic targets., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Multiple sclerosis (MS) is an inflammatory autoimmune disease characterized by neurodegeneration in the CNS. Interferon-beta (IFN-β) is an FDA-approved drug used as the first-line treatment for relapse-remitting multiple sclerosis (RRMS). The exact mechanism of IFN-β during the treatment of RRMS still remains unknown. Recently, many studies have shifted towards the role of miRNAs in the treatment of MS patients., Methods: Herein, the expression level of miR-185-5p and miR-320a has been evaluated in order to candidate them as novel biomarkers for monitoring the response to IFN-β therapy. For this purpose, one-hundred whole blood samples from patients with RRMS were collected, consisting of 50 responders and 50 non-responders to IFN-β therapy. To predict the possible molecular mechanisms of IFN-β and highlight the role of these miRNAs, in silico analysis was applied to enrich the signaling pathways which may be involved based on the target genes of miR-185-5p and miR-320a., Results: It is identified that the differentially expressed miR-185-5p was statistically significant between the two treated groups with IFN-β. Furthermore, MAPK signaling pathway was suggested as the main non-canonical pathway involved in IFN-β therapy., Conclusion: miR-185-5p could be considered as a novel biomarker for monitoring the response to IFN-β therapy., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Podocytes play an essential role in the regulation of glomerular filtration and the appropriate function of the kidney. Podocytes injury is involved in the pathogenesis of nephrotic syndrome (NS), a common renal glomerulus dysfunction characterized by proteinuria. Some in vivo studies in Dicer/Drosha knockout mice indicate the importance of Dicer, Drosha, and microRNAs (miRNAs) in the pathogenesis of NS. In the present study, the expression levels of Dicer and Drosha along with miR-30 family, miR-186, miR-193, and miR-217 were evaluated in peripheral blood mononuclear cell samples of patients with NS (N = 60) using real-time PCR. Dicer expression level in NS patients was significantly upregulated when compared to healthy controls (p = .008). No significant change was observed in the Drosha expression level in the NS group. Upregulated levels of the studied microRNAs were observed in NS group in comparison to controls, the miR-30c-5p (p = .005) and miR-193-3p (p = .041) were statistically significant. In conclusion, dysregulation in expression level of Dicer and Drosha and consequently, alteration in miRNA levels are involved in the pathophysiology of NS., (© 2020 International Union of Biochemistry and Molecular Biology.)

Infertility is a major health problem across the world. One of the main reasons for male infertility are defects in sperm. Semen analysis is the most common test utilized to evaluate male fertility and since it suffers from multiple drawbacks, reproduction scientists have tried to find new molecular markers for detecting sperm defects. MicroRNAs (miRNAs) are small molecules in cells which take part in regulating gene expression. Various studies have confirmed miRNAs to have a role in defining multiple sperm characteristics, including sperm count, motility, and morphology. In this paper, we have systematically reviewed the role of miRNAs in infertile men with sperm defects including azoospermia, oligospermia, asthenozoospermia, and teratozoospermia. Also, we have assembled various bioinformatics tools to come up with a pipeline for predicting novel miRNAs which could possibly participate in sperm count, motility, and morphology. Also, related KEGG and GO terms for predicted miRNAs have been included in order to highlight their role in sperm function. Our study emphasizes the potential role of miRNAs in male infertility and provides a general overview for future studies aiming to find robust molecular markers for this condition.

Multiple sclerosis is immune-mediated disease of the central nervous system characterized by demyelination in axons. IFN-β is first-line treatment of MS. Biomarkers are needed for early prediction of responders and non-responders to therapy in the first month of treatment to avoid further disabilities. In this study, we analyzed the expression level of miR-504 and miR-711 in 52 IFN-β responder patients in comparison to 53 non-responders. In the next step, the in-silico analysis was used to enrich related signaling pathways. The expression level of miR-504 was significantly higher in patients who respond to IFN-β therapy, compared with non-responders and we obtain related statistically significant KEGG molecular signaling pathways. Our findings suggest that miR-504 can be considered as a novel biomarker for response to IFN-b therapy., Competing Interests: Declaration of Competing Interest Authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Cervical cancer (CC) is the fourth most common cause of cancer death in women. The most important risk factor for the development of CC is cervical infection with human papilloma virus (HPV). Inflammation is a protective strategy that is triggered by the host against pathogens such as viral infections that acts rapidly to activate the innate immune response. Inflammation is beneficial if it is brief and well controlled; however, if the inflammation is excessive or it becomes of chronic duration, it can produce detrimental effects. HPV proteins are involved, both directly and indirectly, in the development of chronic inflammation, which is a causal factor in the development of CC. However, other factors may also have a potential role in stimulating chronic inflammation. MicroRNAs (miRNAs) (a class of noncoding RNAs) are strong regulators of gene expression. They have emerged as key players in several biological processes, including inflammatory pathways. Abnormal expression of miRNAs may be linked to the induction of inflammation that occurs in CC. Exosomes are a subset of extracellular vesicles shed by almost all types of cells, which can function as cargo transfer vehicles. Exosomes contain proteins and genetic material (including miRNAs) derived from their parent cells and can potentially affect recipient cells. Exosomes have recently been recognized to be involved in inflammatory processes and can also affect the immune response. In this review, we discuss the role of HPV proteins, miRNAs and exosomes in the inflammation associated with CC., (© 2019 UICC.)

Breast cancer (BC) is one of the widespread lethal diseases affecting a large number of women worldwide. As such, employing and identifying significant markers for detecting BC in different stages can assist in better diagnosis and management of the disease. Several diverse markers have been introduced for diagnosis, but their limitations, including low specificity and sensitivity, reduce their application. microRNAs (miRNAs), as short noncoding RNAs, have been shown to significantly influence gene expression in different disease pathologies, especially BC. Clearly, among different samples used for detecting miRNA expressions, circulating miRNAs present as promising and useful biomarkers. Among different body fluid samples, serum serves as one of the most reliable samples, thanks to its high stability under various severe conditions and some unique features. Extensive research has suggested that BC-related miRNAs can remain stable in the serum. The objective of this review is to describe different samples used for detecting miRNAs in BC subjects with emphasis on serum miRNAs. So, this study highlights serum miRNAs with the potential of acting as biomarkers for different stages of BC. We reviewed the possible correlation between potential miRNAs and the risk of early breast cancer, metastatic breast cancer, response to chemotherapy, and relapse., (© 2019 Wiley Periodicals, Inc.)

In both men and women around the world, lung cancer accounts as the principal cause of cancer-related death after breast cancer. Therefore, early detection of the disease is a cardinal step in improving prognosis and survival of patients. Today, the newly-defined microRNAs regulate about 30 to 60 percent of the gene expression. Changes in microRNA Profiles are linked to numerous health conditions, making them sophisticated biomarkers for timely, if not early, detection of cancer. Though evaluation of microRNAs in real samples has proved to be rather challenging, which is largely attributable to the unique characteristics of these molecules. Short length, sequence similarity, and low concentration stand among the factors that define microRNAs. Recently, diagnostic technologies with a focus on wide-scale point of care have recently garnered attention as great candidates for early diagnosis of cancer. Electrochemical nano-biosensors have recently garnered much attention as a molecular method, showing great potential in terms of sensitivity, specificity and reproducibility, and last but not least, adaptability to point-of-care testing. Application of nanoscale materials in electrochemical devices as promising as it is, brings multiplexing potential for conducting simultaneous evaluations on multiple cancer biomarkers. Thanks to their enthralling properties, these materials can be used to improve the efficiency of cancer diagnostics, offer more accurate predictions of prognosis, and monitor response to therapy in a more efficacious way. This article presents a concise overview of recent advances in the expeditiously evolving area of electrochemical biosensors for microRNA detection in lung cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)