Identification of microRNA-mRNA Regulatory Networks with Therapeutic Values in Alzheimer's Disease by Bioinformatics Analysis.

Background: Alzheimer's disease (AD) is the most prevalent neurological disorder worldwide, affecting approximately 24 million individuals. Despite more than a century of research on AD, its pathophysiology is still not fully understood. Objective: Recently, genetic studies of AD have focused on analyzing the general expression profile by employing high-throughput genomic techniques such as microarrays. Current research has leveraged bioinformatics advancements in genetic science to build upon previous efforts. Methods: Data from the GSE118553 dataset used in this investigation, and the analyses carried out using programs such as Limma and BioBase. Differentially expressed genes (DEGs) and differentially expressed microRNAs (DEmiRs) associated with AD identified in the studied areas of the brain. Target genes of the DEmiRs identified using the MultiMiR package. Gene ontology (GO) completed using the Enrichr website, and the protein-protein interaction (PPI) network for these genes drawn using STRING and Cytoscape software. Results: The findings introduced DEGs including CTNNB1, PAK2, MAP2K1, PNPLA6, IGF1R, FOXL2, DKK3, LAMA4, PABPN1, and GDPD5, and DEmiRs linked to AD (miR-106A, miR-1826, miR-1253, miR-10B, miR-18B, miR-101-2, miR-761, miR-199A1, miR-379 and miR-668), (miR-720, miR-218-2, miR-25, miR-602, miR-1226, miR-548K, miR-H1, miR-410, miR-548F2, miR-181A2), (miR-1470, miR-651, miR-544, miR-1826, miR-195, miR-610, miR-599, miR-323, miR-587 and miR-340), and (miR-1282, miR-1914, miR-642, miR-1323, miR-373, miR-323, miR-1322, miR-612, miR-606 and miR-758) in cerebellum, frontal cortex, temporal cortex, and entorhinal cortex, respectively. Conclusions: The majority of the genes and miRNAs identified by our findings may be employed as biomarkers for prediction, diagnosis, or therapy response monitoring.

The Traces of Dysregulated lncRNAs-Associated ceRNA Axes in Retinoblastoma: A Systematic Scope Review.

PURPOSE: Long non-coding RNAs are an essential component of competing endogenous RNA regulatory axes and play their role by sponging microRNAs and interfering with the regulation of gene expression. Because of the broadness of competing endogenous RNA interaction networks, they may help investigate treatment targets in complicated disorders. METHODS: This study performed a systematic scoping review to assess verified loops of competing endogenous RNAs in retinoblastoma, emphasizing the competing endogenous RNAs axis related to long non-coding RNAs. We used a six-stage approach framework and the PRISMA guidelines. A systematic search of seven databases was done to locate suitable papers published before February 2022. Two reviewers worked independently to screen articles and collect data. RESULTS: Out of 363 records, fifty-one articles met the inclusion criteria, and sixty-three axes were identified in desired articles. The majority of the research reported several long non-coding RNAs that were experimentally verified to act as competing endogenous RNAs in retinoblastoma: XIST/NEAT1/MALAT1/SNHG16/KCNQ1OT1, respectively. At the same time, around half of the studies investigated unique long non-coding RNAs. CONCLUSIONS: Understanding the many features of this regulatory system may aid in elucidating the unknown etiology of Retinoblastoma and providing novel molecular targets for therapeutic and clinical applications.

Identification of differentially expressed genes associated with the pathogenesis of gastric cancer by bioinformatics analysis.

AIM: Gastric cancer (GC) is one of the most diagnosed cancers worldwide. GC is a heterogeneous disease whose pathogenesis has not been entirely understood. Besides, the GC prognosis for patients remains poor. Hence, finding reliable biomarkers and therapeutic targets for GC patients is urgently needed. METHODS: GSE54129 and GSE26942 datasets were downloaded from Gene Expression Omnibus (GEO) database to detect differentially expressed genes (DEGs). Then, gene set enrichment analyses and protein-protein interactions were investigated. Afterward, ten hub genes were identified from the constructed network of DEGs. Then, the expression of hub genes in GC was validated. Performing survival analysis, the prognostic value of each hub gene in GC samples was investigated. Finally, the databases were used to predict microRNAs that could regulate the hub genes. Eventually, top miRNAs with more interactions with the list of hub genes were introduced. RESULTS: In total, 203 overlapping DEGs were identified between both datasets. The main enriched KEGG pathway was "Protein digestion and absorption." The most significant identified GO terms included "primary alcohol metabolic process," "basal part of cell," and "extracellular matrix structural constituent conferring tensile strength." Identified hub modules were COL1A1, COL1A2, TIMP1, SPP1, COL5A2, THBS2, COL4A1, MUC6, CXCL8, and BGN. The overexpression of seven hub genes was associated with overall survival. Moreover, among the list of selected miRNAs, hsa-miR-27a-3, hsa-miR-941, hsa-miR-129-2-3p, and hsa-miR-1-3p, were introduced as top miRNAs targeting more than five hub genes. CONCLUSIONS: The present study identified ten genes associated with GC, which may help discover novel prognostic and diagnostic biomarkers as well as therapeutic targets for GC. Our results may advance the understanding of GC occurrence and progression.

Association of Genetic Polymorphisms in Long Noncoding RNA HOTTIP with Risk of Idiopathic Recurrent Spontaneous Abortion.

The clustered homeobox gene family known as the Hox family plays a fundamental role in the morphogenesis of the vertebrate's embryo. A long noncoding RNA (lncRNA), known as HOTTIP (HOXA transcript at the distal tip), has been functionally characterized and contributed to the pathogenesis of various conditions. The current case-control study was undertaken to examine the gene frequencies and shared alleles of the HOTTIP  gene in Iranian participants with or without idiopathic recurrent spontaneous abortion (RSA). Both ARMS-PCR reaction and RFLP-PCR techniques were employed to detect three HOTTIP polymorphisms (rs2023843C/T, rs78248039A/T, and rs1859168C/A) in a DNA sample of 161 women with RSA and 177 healthy women. We found that the TT genotype of the HOTTIP rs2023843 C/T polymorphism was associated with a lower risk for idiopathic RSA. In contrast, the TT genotype of the HOTTIP rs78248039 A/T polymorphism was correlated with an enhanced risk of RSA. The presence of the A-allele for HOTTIP rs1859168 C/A polymorphism was associated with an increased risk for idiopathic RSA. Haplotype analysis showed that the T/T/A, C/T/A, T/T/C, and T/A/A haplotypes of rs2023843/rs78248039/rs1859168 enhanced RSA susceptibility. Computational analysis predicted that this lncRNA might act as a potential sponge for some microRNAs; therefore, affecting the expression of genes being targeted by them. In addition, both rs2023843 and rs1859168 variants could alter the local secondary structure of HOTTIP. Our results showed that HOTTIP rs2023843C/T, rs78248039A/T, and rs1859168C/A polymorphisms may confer genetic susceptibility to idiopathic RSA in an Iranian population.

The recent development of carbon-based nanoparticles as a novel approach to skin tissue care and management - A review.

Since the skin is the first barrier of the body's defense against pathogens, delays in the healing process are affected by infections. Therefore, applying advanced substitute assistance improves the patient's quality of life. Carbon-based nanomaterials show better capabilities than conventional methods for managing skin wound infections. Due to their physicochemical properties such as small size, large surface area, great surface-to-volume ratio, and excellent ability to communicate with the cells and tissue, carbon-based nanoparticles have been considered in regenerative medicine. moreover, the carbon nano family offers attractive potential in wound healing via the improvement of angiogenesis and antibacterial compared to traditional approaches become one of the particular research interests in the field of skin tissue engineering. This review emphasizes the wound-healing process and the role of carbon-based nanoparticles in wound care management interaction with tissue engineering technology.

The future opportunities and remaining challenges in the application of nanoparticle-mediated hyperthermia combined with chemo-radiotherapy in cancer.

A pivotal cause of death in the modern world, cancer is an insidious pathology that should be diagnosed at an early stage for successful treatment. Development of therapeutic interventions with minimal invasiveness and high efficacy that can discriminate between tumor and normal cells is of particular interest to the clinical science, as they can enhance patient survival. Nanoparticles are an invaluable asset that can be adopted for development of such diagnostic and therapeutic modalities, since they come in very small sizes with modifiable surface, are highly safe and stable, and can be synthesized in a controlled fashion. To date, different nanoparticles have been incorporated into numerous modalities such as tumor-targeted therapy, thermal therapy, chemotherapy, and radiotherapy. This review article seeks to deliver a brief account of recent advances in research and application of nanoparticles in hyperthermia-based cancer therapies. The most recent investigations are summarized to highlight the latest advances in the development of combined thermo-chemo-radiotherapy, along with the challenges associated with the application of nanoparticles in cancer therapy. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Nanotechnology-Based Strategies for Extended-Release Delivery of Angiotensin Receptor Blockers (ARBs): A Comprehensive Review.

There has been a significant shift in the perception of hypertension as an important contributor to the global disease burden. Approximately 6 % and 8 % of pregnancies are affected by hypertension, which can adversely affect the mother and the fetus. Furthermore, a hypertensive individual is at increased risk of developing kidney disease, arterial hardening, eye damage, and strokes. Using angiotensin receptor blockers (ARBs) is widespread in treating hypertension, heart failure, coronary artery disease, and diabetic nephropathy. Despite this, some ARBs have limited use due to their poor oral bioavailability and water solubility. To tackle this, a variety of nanoparticle (NP)-based systems, such as polymeric NPs (i. e., dendrimers), polymeric micelles, polymer-drug conjugates, lipid NPs, nanoemulsions, self-emulsifying drug delivery systems (SEDDS), solid lipid NPs (SLNs), nanostructured lipid carriers (NLCs), carbon-based nanocarriers, inorganic NPs, and nanocrystals, have been recently developed for efficient delivery of losartan, Valsartan (Val), Olmesartan (OLM), Telmisartan (TEL), Candesartan, Eprosartan, Irbesartan, and Azilsartan to target cells. This review article provides a literature-based comparison of the various classes of ARBs, their mechanisms of action, and an overview of the nanoformulations developed for ARB delivery and successfully applied to managing hypertension, diabetic complications, and other conditions.

Promotor methylation in ocular surface squamous neoplasia development: epigenetics implications in molecular diagnosis.

INTRODUCTION: Cancer is heavily influenced by epigenetic mechanisms that include DNA methylation, histone modifications, and non-coding RNA. A considerable proportion of human malignancies are believed to be associated with global DNA hypomethylation, with localized hypermethylation at promoters of certain genes. AREA COVERED: The present review aims to emphasize on recent investigations on the epigenetic landscape of ocular surface squamous neoplasia, that could be targeted/explored using novel approaches such as personalized medicine. EXPERT OPINION: While the former is thought to contribute to genomic instability, promoter-specific hypermethylation might facilitate tumorigenesis by silencing tumor suppressor genes. Ocular surface squamous neoplasia, the most prevalent type of ocular surface malignancy, is suggested to be affected by epigenetic mechanisms, as well. Although the exact role of epigenetics in ocular surface squamous neoplasia has mostly been unexplored, recent findings have greatly contributed to our understanding regarding this pathology of the eye.

Non-coding RNA-mediated epigenetic alterations in Grave's ophthalmopathy: A scoping systematic review.

Background: It is becoming more and more apparent that Grave's Ophthalmopathy (GO) pathogenesis may be aided by epigenetic processes such as DNA methylation modifications, histone tail covalent modifications, and non-coding RNA (ncRNA)-based epigenetic processes. In the present study, we aimed to focus more on the miRNAs rather than lncRNAs due to lack of investigations on these non-coding RNAs and their role in GO's pathogenesis. Methods: A six-stage methodology framework and the PRISMA recommendation were used to conduct this scoping review. A comprehensive search was conducted across seven databases to discover relevant papers published until February 2022. The data extraction separately, and quantitative and qualitative analyses were conducted. Results: A total of 20 articles were found to meet inclusion criteria. According to the results, ncRNA were involved in the regulation of inflammation (miR-146a, LPAL2/miR-1287-5p axis, LINC01820:13/hsa miR-27b-3p axis, and ENST00000499452/hsa-miR-27a-3p axis), regulation of T cell functions (miR-146a/miR-183/miR-96), regulation of glycosaminoglycan aggregation and fibrosis (miR-146a/miR-21), glucocorticoid sensitivity (miR-224-5p), lipid accumulation and adipogenesis (miR-27a/miR-27b/miR-130a), oxidative stress and angiogenesis (miR-199a), and orbital fibroblast proliferation (miR-21/miR-146a/miR-155). Eleven miRNAs (miR-146a/miR-224-5p/miR-Let7d-5p/miR-96-5p/miR-301a-3p/miR-21-5p) were also indicated to have the capacity to be used as biomarkers. Conclusions: Regardless of the fact that there is significant documentation of ncRNA-mediated epigenetic dysfunction in GO, additional study is needed to thoroughly comprehend the epigenetic connections concerned in disease pathogenesis, paving the way for novel diagnostic and prognostic tools for epigenetic therapies among the patients.

Physico-chemical and MR relaxometry study of bovine serum albumin-coated magneto-plasmonic nanoparticles designed for potential use in cancer nanotheranostics.

PURPOSE: In recent years, the use of nanoparticles has been developed to improve MRI contrast. To improve the contrast agents in image-guided therapy by Multifunctional nanoparticles, in this study, we synthesized a theranostic magneto-plasmonic nanocomplex based on magnetic iron oxide nanoparticles and bovine serum albumin-modified gold nanorod (Au@BSA-Fe3O4@CMD). The purpose of synthesizing these nanoparticles was to use them as MRI contrast agent and photothermal agents in in vitro and in vivo experiments. MATERIALS AND METHODS: Initially, the properties of the synthesized nanoparticles were investigated by methods such as DLS, TEM, FTIR. MTT assay was used to evaluate the toxicity of nanoparticles. Finally, to evaluate the contrast ability of nanoparticles, MRI images were taken in in vitro and in vivo conditions and then the images were analyzed. RESULTS: MTT test results on CT26 cell line showed no significant cytotoxicity for Au@BSA-Fe3O4@CMD nanoparticles at concentrations up to 20 ppm. The in vitro results demonstrated that the Au@BSA-Fe3O4@CMD nanocomplex has high T2 relaxation rate and great relaxivities (r2 = 140.14 mM-1 s-1, r1 = 2.066 mM-1 s-1, r2/r1 = 67.83). For in vivo conditions, a decrease in T2 signal of 9.64 and 11.01, respectively, was observed for intratumoral and intraperitoneal injection of nanoparticles. CONCLUSION: These in vitro and in vivo studies show that Au @ BSA-Fe3O4@CMD nanoparticles can significantly reduce the signal intensity of T2-weight MRI images, and therefore can offer significant potential as a theranostic platform for effective tumor MR imaging.

Aptamer-functionalized quantum dots as theranostic nanotools against cancer and bacterial infections: A comprehensive overview of recent trends.

Aptamers (Apts) are synthetic nucleic acid ligands that can be engineered to target various molecules, including amino acids, proteins, and pharmaceuticals. Through a series of adsorption, recovery, and amplification steps, Apts are extracted from combinatorial libraries of synthesized nucleic acids. Using aptasensors in bioanalysis and biomedicine can be improved by combining them with nanomaterials. Moreover, Apt-associated nanomaterials, including liposomes, polymeric, dendrimers, carbon nanomaterials, silica, nanorods, magnetic NPs, and quantum dots (QDs), have been widely used as promising nanotools in biomedicine. Following surface modifications and conjugation with appropriate functional groups, these nanomaterials can be successfully used in aptasensing. Advanced biological assays can use Apts immobilized on QD surfaces through physical interaction and chemical bonding. Accordingly, modern QD aptasensing platforms rely on interactions between QDs, Apts, and targets to detect them. QD-Apt conjugates can be used to directly detect prostate, ovarian, colorectal, and lung cancers or simultaneously detect biomarkers associated with these malignancies. Tenascin-C, mucin 1, prostate-specific antigen, prostate-specific membrane antigen, nucleolin, growth factors, and exosomes are among the cancer biomarkers that can be sensitively detected using such bioconjugates. Furthermore, Apt-conjugated QDs have shown great potential for controlling bacterial infections such as Bacillus thuringiensis, Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, Campylobacter jejuni, Staphylococcus aureus, and Salmonella typhimurium. This comprehensive review discusses recent advancements in the design of QD-Apt bioconjugates and their applications in cancer and bacterial theranostics.

An update in the applications of exosomes in cancer theranostics: from research to clinical trials.

Exosomes are nanosized extracellular vesicles secreted by nearly all viable cells following the fusing of multivesicular bodies and the plasma membrane and discharged into the encircling bodily fluids. Exosomes can transport cell-specific components from the source cell to the target cell. Given the enormous potential of exosomes as non-invasive diagnostic biomarkers and therapeutic nanovehicles. Lately, accumulated evidence has demonstrated that exosomes serve an important role in prognosis, diagnosis, and even treatment strategies. While several reviews have collective information on the biomedical application of exosomes, a comprehensive review incorporating updated and improved methodologies for beneficial applications of such vesicles in cancer theranostics is indispensable. In the current review, we first provided a comprehensive review of the introduction of exosomes, featuring their discovery, separation, characterization, function, biogenesis, secretion. The implications of exosomes as promising nanovehicles for drug and gene delivery, application of exosome inhibitors in the management of cancers, completed and ongoing clinical trials on the biological relevance of exosomes are then discussed in detail. As the field of exosome research grows, a better understanding of the subcellular parts and mechanisms involved in exosome secretion and targeting of specific cells will help figure out what their exact physiological functions are in the body.

Bioinformatic Analysis Divulged Novel Prognostic Circulating MicroRNAs and Their Potential Target Genes in Breast Cancer.

Breast cancer (BC) is both an inherited and environmental-based disease which is the leading cause of death among women. Early detection of BC can prevent invasion and metastasis in patients. Currently, researchers endeavor to find non-invasive biological markers from body fluids. Circulating non-coding RNAs such as microRNAs (miRNAs) can potentially be valuable prognostic and detective biomarkers. To identify novel miRNA-based biomarkers, we utilized bioinformatic tools. To reach this goal, the miRNA expression profiles of GSE31309, GSE 44,281, GSE98181, and GSE118782 were analyzed through a limma package of R. Target gene prediction of differentially expressed miRNAs, called differentially expressed miRNAs (DEMs), between samples of healthy individuals and BC patients was implemented through Multimir package of R. Functional enrichment analysis of predicted target genes through Enrich R (online database) revealed that most of the genes are enriched in the mitochondrial outer membrane for cellular component, intrinsic apoptotic signaling regulations for biological processes, transcription co-receptor activity for molecular functions, and dopaminergic synapse pathway. Furthermore, our survival analysis results revealed that miR-29c and mir-361 have the potential to serve as prognostic biomarkers.

Development and classification of RNA aptamers for therapeutic purposes: an updated review with emphasis on cancer.

Today, RNA aptamers are being considered promising theranostic tools against a wide variety of disorders. RNA aptamers can fold into complex shapes and bind to diverse nanostructures, macromolecules, cells, and viruses. It is possible to isolate RNA aptamers from a vast pool of nucleic acids via the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) method. As therapeutics, aptamers have great potential because of their ability to bind to proteins and selectively limit their activities with negligible side effects. Several RNA aptamers with potential implications in cancer diagnosis are known to confer a great affinity for single-stranded DNA molecules, long non-coding RNAs, circulating tumor cells, vascular endothelial growth factors, and tissue and sera-derived exosomes in patients with different malignancies. Furthermore, clinical investigations have revealed the efficacy of RNA aptamer-based agents in imaging modalities. This review seeks to deliver new insights into the development, classification, nanomerization, and modification of RNA aptamers, as well as their applications in cancer theranostics. The aptamers' mechanism of action and their interest to clinical trials as theranostic agents are also discussed.

Diagnostic accuracy of clinically applied nanoparticle-based biosensors at detecting SARS-CoV-2 RNA and surface proteins in pharyngeal swabs compared to RT-PCR as a reference test.

INTRODUCTION: Nanoparticle-based biosensors (NPBs) are point-of-care diagnostic platforms that can be used for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with high accuracy. AREAS COVERED: EBSCOhost Web, Embase, ProQuest, PubMed/MEDLINE, Scopus, Web of Science, and WHO Global Literature on Coronavirus Disease 2019 (COVID-19) were searched for relevant records published from 1 November 2019 to 30 April 2022. Records reporting original data on the accuracy of clinically applied nanoparticle-based biosensors at detecting SARS-CoV-2 RNA and surface proteins from pharyngeal swab specimens were considered. Findings were reported based on the PRISMA 2020 statement. The QUADAS-2 tool was used for assessment of quality and risk of bias among the included studies. EXPERT OPINION: A total of 50 relevant records were identified, of which 13 were included. The included studies explored the diagnostic performance of 13 clinically applied distinct nanoparticle-based biosensors in a total of 789 pharyngeal swabs collected from 376 COVID-19 patients and 413 otherwise healthy individuals. The mean sensitivity, specificity, and accuracy were 97.07%, 94.43%, and 96.91%, respectively, in comparison to RT-qPCR as the reference test. Considering their ease-of-operation, portability, low-cost manufacturing, NPBs could be considered suitable candidate diagnostic platforms for substituting RT-qPCR.

Short-term celecoxib (celebrex) adjuvant therapy: a clinical trial study on COVID-19 patients.

BACKGROUND: It is known that severe acute respiratory coronavirus 2 (SARS-CoV-2) is the viral strain responsible for the recent coronavirus disease 2019 (COVID-19) pandemic. Current documents have demonstrated that the virus causes a PGE2 storm in a substantial proportion of patients via upregulating cyclooxygenase-2 (COX-2) and downregulating prostaglandin E2 (PGE2)-degrading enzymes within the host cell. AIM: Herein, we aimed to study how short-term treatment with celecoxib (Celebrex), a selective COX-2 inhibitor, affects demographic features, early symptoms, O2 saturation, and hematological indices of cases with COVID-19. METHODS: A total of 67 confirmed COVID-19 cases with a mild or moderate disease, who had been referred to an institutional hospital in south-eastern Iran from October 2020 to September 2021, were enrolled. Demographic characteristics, symptoms, and hematological indices of the patients were recorded within different time periods. One-way ANOVA or Kruskal-Wallis tests were used to determine differences between data sets based on normal data distribution. RESULTS: O2 saturation was statistically different between the control group and patients receiving celecoxib (p = 0.039). There was no marked difference between the groups in terms of the symptoms they experienced (p > 0.05). On the first days following Celebrex therapy, analysis of complete blood counts showed that white blood cell (WBC) counts were markedly lower in patients treated with a high dose of celecoxib (0.4 g/day) than in controls (p = 0.026). However, mean lymphocyte levels in patients receiving a high dose of celecoxib (0.4 g/day) were markedly higher than in patients receiving celecoxib with half of the dose (0.2 g/day) for one week or the untreated subjects (p = 0.004). Changes in platelet count also followed the WBC alteration pattern. CONCLUSION: Celecoxib is a relatively safe, inexpensive, and widely available drug with non-steroidal anti-inflammatory properties. The therapeutic efficacy of celecoxib depends on the administrated dose. Celecoxib might improve disease-free survival in patients with COVID-19.

Effects of folate-conjugated Fe2O3@Au core-shell nanoparticles on oxidative stress markers, DNA damage, and histopathological characteristics: evidence from in vitro and in vivo studies.

The aim of this work was to assess the cytotoxicity, genotoxicity, and histopathological effects of Fe2O3@Au-FA NPs using in vitro and in vivo models. Cytotoxicity and cellular uptake of nanoparticles (NPs) by HUVECs were examined via 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and inductively coupled plasma-mass-spectrometry (ICP-MS). This safe dose was then used for cytotoxicity assays, including total protein, total antioxidant capacity, lipid peroxidation, cell membrane integrity, reactive oxygen species, enzyme activity, and DNA damage. In the animal model, 32 Wistar rats were randomly categorized into 4 groups and received intraperitoneal injections of NPs. Blood samples for biochemical properties and histopathological changes were investigated. MTT results indicated 20 µg/ml as the safe dose for NPs. According to ICP-MS, treated cells showed significantly higher levels of the intracellular content of Fe (p < 0.001) and Au (p < 0.01) compared with the control group. In vitro tests did not show any significant cytotoxicity or genotoxicity at the safe dose of NPs. We found no significant elevation in intracellular γ-H2AX levels after treatment of HUVEC cells with Fe2O3@Au core-shell NPs (P > 0.05). As for the in vivo analysis, we observed no marked difference in serum biochemical parameters of rats treated with 50 mg/kg and 100 mg/kg doses of our NPs. Histopathological assessments indicated that liver, kidney, and testis tissues were not significantly affected at 50 mg/kg (liver), 50 mg/kg, and 100 mg/kg (kidney and testis) on NPs administration. These findings imply that the nanotoxicity of Fe2O3@Au-FA NPs in HUVECs and animals depends largely on the administrated dose. Our study suggests that Fe2O3@Au-FA NPs at a safe dose could be considered as new candidates in nanobiomedicine.

WITHDRAWN: In silico and Experimental Analysis of miR-125b-5 and miR-485-5p Expression in Serum of Patients with Breast Cancer

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Long noncoding RNA HOTAIR polymorphisms and susceptibility to bipolar disorder: a preliminary case-control study.

Recent studies have shown that long noncoding RNAs contribute to the pathogenesis of bipolar disorder (BD). In this study, we genotyped four HOX Transcript Antisense Intergenic RNA (HOTAIR) gene polymorphisms to investigate if these variations could affect the risk of BD and its clinical subtypes. A total of 357 subjects, comprised of 194 BD patients and 163 age-matched healthy controls, were enrolled. Genotyping was carried out using PCR-RFLP and ARMS-PCR methods. We detected significant associations between the HOTAIR gene rs1899663 G/T, rs12826786 C/T, rs4759314 A/G, and rs920778 C/T polymorphism and the risk of BD under allelic, recessive, dominant, and codominant contrasted genetic models. The CT genotype of rs920778 C/T, GT genotype of rs1899663 G/T, and CT genotype of rs12826786 C/T polymorphisms enhanced the risk of BD type II (BDII). In contrast, the GG genotype of rs4759314 A/G polymorphism significantly diminished BDII risk by 83%. A positive association was noticed between CTTA and CTCG haplotypes of rs920778/rs1899663/rs12826786/rs4759314 and BD risk. Our findings reveal an interactive effect of HOTAIR polymorphisms on the development of BD and its subtypes. Further functional studies are needed to elucidate the role of these variations on HOTAIR expression and epigenetic status.

Association of Polymorphisms within HOX Transcript Antisense RNA (HOTAIR) with Type 2 Diabetes Mellitus and Laboratory Characteristics: A Preliminary Case-Control Study.

Type 2 diabetes mellitus (T2DM) is a complex heterogeneous disease resulting from the environment and genetic interactions. Lately, genetic association studies have shown that polymorphisms in long noncoding RNAs (lncRNAs) are associated with T2DM susceptibility. This preliminary study is aimed at investigating if HOX transcript antisense RNA (HOTAIR) polymorphisms contribute to T2DM development. Five hundred clinically diagnosed T2DM cases and 500 healthy controls were recruited from the southeast Iranian population. Genomic DNA was isolated from nucleated blood cells and genotyped for MspI (C/T) (rs920778) and AluI (A/G) (rs4759314) polymorphisms using the PCR-RFLP technique. For genotyping rs12826786 C/T and rs1899663 G/T variants, ARMS-PCR method was applied. Our findings indicated that HOTAIR rs920778 C/T, rs12826786 C/T, and rs4759314 A/G polymorphisms have a significant positive association with T2DM, while a negative association was observed between rs1899663 G/T T2DM susceptibility. Significant associations were also observed between rs920778 C/T and HDL-C as well as s4759314 A/G and both FBS and LDL-C in T2DM patients. Haplotype analysis indicated that the CGCG, CTTG, TGTA, and TTTG haplotypes of rs920778/rs1899663/rs12826786/rs4759314 significantly enhanced T2DM risk by 1.47, 1.96, 2.81, and 4.80 folds, respectively. No strong linkage disequilibrium was found between the four HOTAIR SNPs. We firstly reported that HOTAIR rs1899663 G/T, rs12826786 C/T, rs4759314 A/G, and rs920778 C/T polymorphisms might influence T2DM susceptibility by modulating different signaling pathways and could be regarded as potential prognostic markers in T2DM patients.