A comprehensive review of online resources for microRNA-diseases associations: the state of the art.

MicroRNAs (miRNAs) as small 19- to 24-nucleotide noncoding RNAs regulate several mRNA targets and signaling pathways. Therefore, miRNAs are considered key regulators in cellular pathways as well as various pathologies. There is substantial interest in the relationship between disease and miRNAs, which made that one of the important research topics. Interestingly, miRNAs emerged as an attractive approach for clinical application, not only as biomarkers for diagnosis and prognosis or in the prediction of therapy response but also as therapeutic tools. For these purposes, the identification of crucial miRNAs in disease is very important. Databases provided valuable experimental and computational miRNAs-disease information in an accessible and comprehensive manner, such as miRNA target genes, miRNA related in signaling pathways and miRNA involvement in various diseases. In this review, we summarized miRNAs-disease databases in two main categories based on the general or specific diseases. In these databases, researchers could search diseases to identify critical miRNAs and developed that for clinical applications. In another way, by searching particular miRNAs, they could recognize in which disease these miRNAs would be dysregulated. Despite the significant development that has been done in these databases, there are still some limitations, such as not being updated and not providing uniform and detailed information that should be resolved in future databases. This survey can be helpful as a comprehensive reference for choosing a suitable database by researchers and as a guideline for comparing the features and limitations of the database by developer or designer. Short abstract We summarized miRNAs-disease databases that researchers could search disease to identify critical miRNAs and developed that for clinical applications. This survey can help choose a suitable database for researchers.

Targeting PCSK9 as a key player in lipid metabolism: exploiting the therapeutic and biosensing potential of aptamers.

The degradation of low-density lipoprotein receptor (LDLR) is induced by proprotein convertase subtilisin/kexin type 9 (PCSK9), resulting in elevated plasma concentrations of LDL cholesterol. Therefore, inhibiting the interactions between PCSK9 and LDLR is a desirable therapeutic goal for managing hypercholesterolemia. Aptamers, which are RNA or single-stranded DNA sequences, can recognize their targets based on their secondary structure. Aptamers exhibit high selectivity and affinity for binding to target molecules. The systematic evolution of ligands by exponential enrichment (SELEX), a combination of biological approaches, is used to screen most aptamers in vitro. Due to their unique advantages, aptamers have garnered significant interest since their discovery and have found extensive applications in various fields. Aptamers have been increasingly utilized in the development of biosensors for sensitive detection of pathogens, analytes, toxins, drug residues, and malignant cells. Furthermore, similar to monoclonal antibodies, aptamers can serve as therapeutic tools. Unlike certain protein therapeutics, aptamers do not elicit antibody responses, and their modified sugars at the 2'-positions generally prevent toll-like receptor-mediated innate immune responses. The focus of this review is on aptamer-based targeting of PCSK9 and the application of aptamers both as biosensors and therapeutic agents.

Impact of curcumin on ferroptosis-related genes in colorectal cancer: Insights from in-silico and in-vitro studies.

Colorectal cancer (CRC) is responsible for a significant number of cancer-related fatalities worldwide. Researchers are investigating the therapeutic potential of ferroptosis, a type of iron-dependent controlled cell death, in the context of CRC. Curcumin, a natural compound found in turmeric, exhibits anticancer properties. This study explores the effects of curcumin on genes related to ferroptosis (FRGs) in CRC. To gather CRC data, we used the Gene Expression Profiling Interactive Analysis (GEPIA) and Gene Expression Omnibus (GEO) databases, while FRGs were obtained from the FerrDb database and PubMed. We identified 739 CRC differentially expressed genes (DEGs) in CRC and discovered 39 genes that were common genes between FRGs and CRC DEGs. The DEGs related to ferroptosis were enriched with various biological processes and molecular functions, including the regulation of signal transduction and glucose metabolism. Using the Drug Gene Interaction Database (DGIdb), we predicted drugs targeting CRC-DEGs and identified 17 potential drug targets. Additionally, we identified eight essential proteins related to ferroptosis in CRC, including MYC, IL1B, and SLC1A5. Survival analysis revealed that alterations in gene expression of CDC25A, DDR2, FABP4, IL1B, SNCA, and TFAM were associated with prognosis in CRC patients. In SW480 human CRC cells, treatment with curcumin decreased the expression of MYC, IL1B, and EZH2 mRNA, while simultaneously increasing the expression of SLCA5 and CAV1. The findings of this study suggest that curcumin could regulate FRGs in CRC and have the potential to be utilized as a therapeutic agent for treating CRC.

In vitro attrition wear resistance of four types of paste-like bulk-fill composite resins.

BACKGROUND: Recently, the application of bulk-fill composite resins has increased significantly. Attrition wear and the consequently increased surface roughness of composite resins are among the causes of restoration failure in the posterior teeth. This study aimed to compare the attrition wear and surface roughness of four types of bulk-fill composite resins compared to a conventional composite resin. METHODS: EverX-Posterior, X-tra fil, SonicFill 2, and Filtek Bulk-Fill composites (bulk-fill) and Z250 composite (conventional resin composite) were evaluated. Thirty cylindrical specimens (n = 6) were weighed and monitored for 24 h until their weight was stabilized. The primary surface roughness of the specimens was measured by a profilometer. The specimens were then subjected to attrition wear in a chewing simulator. Next, the specimens were weighed, and the surface roughness was measured again. Data were analyzed by one-way ANOVA and Tukey's post-hoc test at P < 0.05 significance level. RESULTS: According to one-way ANOVA, the difference in weight loss was significant among the groups (P = 0.004) but the difference in surface roughness of the groups was not significant after the attrition wear (P > 0.05). Tukey's post-hoc test showed that the weight loss of bulk-fill composites was not significantly different from that of Z250 conventional composite after the attrition wear (P > 0.05). CONCLUSION: Within the limitations of this study, it appears that the tested bulk-fill composite resins are comparable to the conventional composite regarding their attrition wear, increased surface roughness, and weight loss.

Effects of therapeutic probiotics on modulation of microRNAs.

Probiotics are beneficial bacteria that exist within the human gut, and which are also present in different food products and supplements. They have been investigated for some decades, due to their potential beneficial impact on human health. Probiotics compete with pathogenic microorganisms for adhesion sites within the gut, to antagonize them or to regulate the host immune response resulting in preventive and therapeutic effects. Therefore, dysbiosis, defined as an impairment in the gut microbiota, could play a role in various pathological conditions, such as lactose intolerance, gastrointestinal and urogenital infections, various cancers, cystic fibrosis, allergies, inflammatory bowel disease, and can also be caused by antibiotic side effects. MicroRNAs (miRNAs) are short non-coding RNAs that can regulate gene expression in a post-transcriptional manner. miRNAs are biochemical biomarkers that play an important role in almost all cellular signaling pathways in many healthy and disease states. For the first time, the present review summarizes current evidence suggesting that the beneficial properties of probiotics could be explained based on the pivotal role of miRNAs. Video Abstract.

Androgen receptor-related micro RNAs in prostate cancer and their role in antiandrogen drug resistance.

Prostate cancer (PCa) is one of the most common cancers and the fifth most common reason for cancer deaths in the males. Surgical castration combined with androgen deprivation therapy, antiandrogens, and androgen synthesis inhibitors is the current therapeutic modalities for PCa. These strategies inhibit androgen synthesis or reduce its binding to the androgen receptor (AR) but the development of resistance to these therapies and transient responsiveness are challenging issues in the treatment of this cancer. Deregulation of ARs has a vital role in the initiation and progression of PCa. Also, recent findings imply that micro RNAs (miRNAs) are involved in the evolution of PCa and mediate drug resistance in different cancers. Hence, discovering and targeting miRNAs might represent a novel therapeutic approach. This review paid particular attention to the AR pathway and existing information on the possible roles of miRNAs associated with AR pathway and drug resistance to two second-generation antiandrogens, that is, enzalutamide and abiraterone.

Electrochemical-based biosensors for microRNA detection: Nanotechnology comes into view.

Nanotechnology plays an undeniable significant role in medical sciences, particularly in the field of biomedicine. Development of several diagnostic procedures in medicine has been possible through the beneficial application of nano-materials, among which electrochemical nano-biosensors can be mentioned. They can be employed to quantify various clinical biomarkers in detection, evaluation, and follow up stages of the illnesses. MicroRNAs, a group of regulatory short RNA fragments, added a new dimension to the management and diagnosis of several diseases. Mature miRNAs are single-stranded RNA molecules approximately 22 nucleotides in length, which regulate a vast range of biological functions from cellular proliferation and death to cancer development and progression. Recently, diagnostic value of miRNAs in various diseases has been demonstrated. There are many traditional methods for detection of miRNAs including northern blotting, quantitative real time PCR (qRT-PCR), microarray technology, nanotechnology-based approaches, and molecular biology tools including miRNA biosensors. In comparison with other techniques, electrochemical nucleic acid biosensor methods exhibit many interesting features, and could play an important role in the future nucleic acid analysis. This review paper provides an overview of some different types of nanotechnology-based biosensors for detection of miRNAs.

Nanospheres for curcumin delivery as a precision nanomedicine in cancer therapy.

Cancer is ranked among the top causes of mortality throughout the world. Conventional therapies are associated with toxicity and undesirable side effects, rendering them unsuitable for prolonged use. Additionally, there is a high occurrence of resistance to anticancer drugs and recurrence in certain circumstances. Hence, it is essential to discover potent anticancer drugs that exhibit specificity and minimal unwanted effects. Curcumin, a polyphenol derivative, is present in the turmeric plant (Curcuma longa L.) and has chemopreventive, anticancer, radio-, and chemo-sensitizing activities. Curcumin exerts its anti-tumor effects on cancer cells by modulating the disrupted cell cycle through p53-dependent, p53-independent, and cyclin-dependent mechanisms. This review provides a summary of the formulations of curcumin based on nanospheres, since there is increasing interest in its medicinal usage for treating malignancies and tumors. Nanospheres are composed of a dense polymeric matrix, and have a size ranging from 10 to 200 nm. Lactic acid polymers, glycolic acid polymers, or mixtures of them, together with poly (methyl methacrylate), are primarily used as matrices in nanospheres. Nanospheres are suitable for local, oral, and systemic delivery due to their minuscule particle size. The majority of nanospheres are created using polymers that are both biocompatible and biodegradable. Previous investigations have shown that the use of a nanosphere delivery method can enhance tumor targeting, therapeutic efficacy, and biocompatibility of different anticancer agents. Moreover, these nanospheres can be easily taken up by mammalian cells. This review discusses the many curcumin nanosphere formulations used in cancer treatment.

Dysregulated microRNAs in prostate cancer: In silico prediction and in vitro validation.

Objectives: MicroRNAs, which are micro-coordinators of gene expression, have been recently investigated as a potential treatment for cancer. The study used computational techniques to identify microRNAs that could target a set of genes simultaneously. Due to their multi-target-directed nature, microRNAs have the potential to impact multiple key pathways and their pathogenic cross-talk. Materials and Methods: We identified microRNAs that target a prostate cancer-associated gene set using integrated bioinformatics analyses and experimental validation. The candidate gene set included genes targeted by clinically approved prostate cancer medications. We used STRING, GO, and KEGG web tools to confirm gene-gene interactions and their clinical significance. Then, we employed integrated predicted and validated bioinformatics approaches to retrieve hsa-miR-124-3p, 16-5p, and 27a-3p as the top three relevant microRNAs. KEGG and DIANA-miRPath showed the related pathways for the candidate genes and microRNAs. Results: The Real-time PCR results showed that miR-16-5p simultaneously down-regulated all genes significantly except for PIK3CA/CB in LNCaP; miR-27a-3p simultaneously down-regulated all genes significantly, excluding MET in LNCaP and PIK3CA in PC-3; and miR-124-3p could not down-regulate significantly PIK3CB, MET, and FGFR4 in LNCaP and FGFR4 in PC-3. Finally, we used a cell cycle assay to show significant G0/G1 arrest by transfecting miR-124-3p in LNCaP and miR-16-5p in both cell lines. Conclusion: Our findings suggest that this novel approach may have therapeutic benefits and these predicted microRNAs could effectively target the candidate genes.

Therapeutic potential of decoys for prostate cancers: A review of recent updates.

Prostate cancer is ranked second among the most common male cancers. Androgen deprivation therapy (ADT) has long been the first-line treatment and the basis for all other therapies, reducing circulating androgens to castration levels and preventing disease development. Nevertheless, ADT monotherapy may not always limit disease development, and even at low testosterone levels, hormone-sensitive prostate cancer will become castration-resistant. Recent research demonstrates that prostate cancer can have a range of potentially actionable genetic abnormalities; no medications that target these variations have yet been shown to elicit therapeutic advantages. Despite their established efficacy in the management of other cancers, advanced genetic or immunological approaches are not regularly used to treat prostate cancer patients. As a result, there is an unmet demand for medicines that offer a better chance of survival than the existing castration-resistance prostate cancer (CRPC) therapy regimens. The use of oligodeoxynucleotides (ODN) and peptides in decoy technology have been developed as novel therapeutic approaches. Decoy ODNs bind to a particular transcription factor with high affinity and may suppress gene transcription. Peptide decoys bind to specific ligands with high specificity and inhibit signaling pathways. Recent evidence supports the notion that these techniques are promising and attractive in the fight against cancer. In the present review, we discuss the use of decoy technology as a novel therapeutic approach against prostate cancer.

Harnessing the Therapeutic Potential of Antimicrobial Peptides for Cancers: State of the Art.

Despite significant breakthroughs in cancer treatment, cancer remains a serious global health concern that takes thousands of lives each year. Still, drug resistance and adverse effects are the main problems in conventional cancer therapeutic approaches. Thus, the discovery of new anticancer agents with distinct mechanisms of action is a critical requirement that offers significant obstacles. Antimicrobial peptides (AMPs), which can be found in various forms of life, are recognized as defensive weapons against infections of microbial pathogens. Surprisingly, they are also capable of killing a variety of cancer cells. These powerful peptides can cause cell death in the gastrointestinal, urinary tract, and reproductive cancer cell lines. To emphasize the anti-cancer properties of AMPs, we summarize the research that examined their impact on cancer cell lines in this review.

Decoys as potential therapeutic tools for diabetes.

Current therapeutic approaches for diabetes are focused on improving glycemic control to prevent diabetes-related complications, but such approached are not completely successful. Decoy technologies such as decoy oligodeoxynucleotides (ODNs) and decoy peptides have emerged as therapeutic tools in diabetes. Decoy ODNs carry a DNA recognition motif for the binding of transcription factors in order to trap them and block their effects, whereas decoy peptides mimic the binding structure of the receptor protein, bind to the docking site of the target ligand, and prevent the interaction of the ligand and receptor. This review summarizes the technologies that have been developed to date and the studies that have investigated the therapeutic effects of decoy ODNs and peptides in diabetes.

New epigenetic players in stroke pathogenesis: From non-coding RNAs to exosomal non-coding RNAs.

Non-coding RNAs (ncRNAs) have critical role in the pathophysiology as well as recovery after ischemic stroke. ncRNAs, particularly microRNAs, and the long non-coding RNAs (lncRNAs) are critical for angiogenesis and neuroprotection, and they have been suggested to be therapeutic, diagnostic and prognostic tools in cerebrovascular diseases, including stroke. Moreover, exosomes have been considered as nanocarriers capable of transferring various cargos, such as lncRNAs and miRNAs to recipient cells, with prominent inter-cellular roles in the mediation of neuro-restorative events following strokes and neural injuries. In this review, we summarize the pathogenic role of ncRNAs and exosomal ncRNAs in the stroke.

Joint application of biochemical markers and imaging techniques in the accurate and early detection of glioblastoma.

Glioblastoma is a primary brain tumor with the most metastatic effect in adults. Despite the wide range of multidimensional treatments, tumor heterogeneity is one of the main causes of tumor spread and gives great complexity to diagnostic and therapeutic methods. Therefore, featuring noble noninvasive prognostic methods that are focused on glioblastoma heterogeneity is perceived as an urgent need. Imaging neuro-oncological biomarkers including MGMT (O6-methylguanine-DNA methyltransferase) promoter methylation status, tumor grade along with other tumor characteristics and demographic features (e.g., age) are commonly referred to during diagnostic, therapeutic and prognostic processes. Therefore, the use of new noninvasive prognostic methods focused on glioblastoma heterogeneity is considered an urgent need. Some neuronal biomarkers, including the promoter methylation status of the promoter MGMT, the characteristics and grade of the tumor, along with the patient's demographics (such as age and sex) are involved in diagnosis, treatment, and prognosis. Among the wide array of imaging techniques, magnetic resonance imaging combined with the more physiologically detailed technique of H-magnetic resonance spectroscopy can be useful in diagnosing neurological cancer patients. In addition, intracranial tumor qualitative analysis and sometimes tumor biopsies help in accurate diagnosis. This review summarizes the evidence for biochemical biomarkers being a reliable biomarker in the early detection and disease management in GBM. Moreover, we highlight the correlation between Imaging techniques and biochemical biomarkers and ask whether they can be combined.

Decoy oligodeoxynucleotide technology: an emerging paradigm for breast cancer treatment.

Breast cancer is the most common cancer in women worldwide. Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer, which is resistant to conventional therapies. Therefore, there is an urgent need to identify new therapies for treating incurable breast cancer in patients. Decoy oligodeoxynucleotides (ODNs) are synthetic oligonucleotides that have a high affinity for a specific transcription factor and can be transfected into target cells to bind to their respective target and alter gene transcription. With these powerful tools available, it is highly possible to effectively regulate the expression of genes that are involved in the pathogenesis of breast cancer. Here, we highlight the studies using decoy ODNs for the development of novel therapies against breast cancer.

Circular RNAs: New players in thyroid cancer.

The prevalence of thyroid cancer the most frequent endocrine malignancy, is rapidly increasing. Most of thyroid cancers are relatively indolent, however, some cases still possess a risk of developing into lethal types of thyroid cancer. Regarding its multistep tumorigenesis, the determination of the underlying mechanisms is a vital issue for thyroid cancer therapy. Circular RNAs (circRNAs) are a type of non-coding RNAs with a closed loop structure. Numerous circRNAs have been identified in cancerous tissues. Mounting data recommends that the biological activities of circRNAs, such as serving as microRNA or ceRNAs sponges, interacting with proteins, modulating gene translation and transcription, suggesting that circRNAs will be potential targets as well as agents for the prognosis and diagnosis of diseases, including cancer. Given that circular RNAs acts as oncogenes or tumor suppressors in the thyroid cancer. Several studies documented that circular RNAs via microRNA and protein sponges could regulate a sequences of cellular and molecular mechanisms e.g., apoptosis, angiogenesis, tumor growth, and invasion that are involved in thyroid cancer pathogenesis. Herein, we summarized the role of circular RNAs as therapeutic and diagnostic biomarkers in the thyroid cancer. Moreover, we highlighted the role of these molecules in the pathogenesis of various cancers.

Peptide decoys: a new technology offering therapeutic opportunities for breast cancer.

Breast cancer is the most common cancer among women. Absence of hormone receptors (estrogen and progesterone) and lack of overexpression of Human Epidermal Growth Factor 2 (HER2) make triple-negative breast cancer (TNBC) an aggressive subtype of breast cancer that is resistant to conventional therapies. Peptide decoys have emerged as a novel therapeutic approach for the treatment of breast cancer. Decoy peptide technology entails the use of soluble proteins or peptides, including binding proteins or inactive cell surface receptors. Peptide decoys bind to certain ligands (e.g., inflammatory cytokines) with high affinity and specificity as receptors but cannot initiate any signaling pathway that is involved in the pathogenesis of breast cancer. In this review, we discuss the use of decoy peptides as a novel therapeutic approach for breast cancer treatment.

Autophagy-related MicroRNAs in chronic lung diseases and lung cancer.

Chronic lung disease has become a leading cause of death in recent years. Despite several attempts to discover and develop new therapeutic approaches, patients often suffer a poor quality of life, and are faced with an increased risk of developing lung cancer. Lung cancer often occurs as an end-stage after years of chronic lung disease. An increased understanding of the pathophysiology of chronic lung disease may be obtained from studying the role of autophagy in its initiation and progression. MicroRNAs (miRNAs) play a critical role in the modulation of autophagy, and their deregulation could be associated with the initiation and progression of several chronic lung diseases. Herein, we documented that up/down regulation of miRNAs can activate or inhibit autophagy in chronic lung diseases including lung cancer. Therefore, theses miRNAs could be a promising therapeutic tool for lung cancer specially in drug-resistance lung cancer cells.

Electrochemical-Based Biosensors: New Diagnosis Platforms for Cardiovascular Disease.

One of the major reasons for mortality throughout the world is cardiovascular diseases. Therefore, bio-markers of cardiovascular disease are of high importance to diagnose and manage procedure. Detecting biomarkers provided a promising procedure in developing bio-sensors. Fast, selective, portable, accurate, inexpensive, and sensitive biomarker sensing instruments will be necessary for detecting and predicting diseases. One of the cardiac biomarkers may be ordered as C-reactive proteins, lipoprotein-linked phospho-lipase, troponin I or T, myoglobin, interleukin-6, interleukin-1, tumor necrosis factor alpha, LDL and myeloperoxidase. The biomarkers are applied to anticipate cardio-vascular illnesses. Initial diagnoses of these diseases are possible by several techniques; however, they are laborious and need costly apparatus. Current researches designed various bio-sensors for resolving the respective issues. Electrochemical instruments and the proposed bio-sensors are preferred over other methods due to its inexpensiveness, mobility, reliability, repeatability. The present review comprehensively dealt with detecting biomarkers of cardiovascular disease through electro-chemical techniques.

Polymerization Shrinkage of Five Bulk-Fill Composite Resins in Comparison with a Conventional Composite Resin.

OBJECTIVES: The polymerization shrinkage of methacrylate-based composites is among the most important causes of failure of composite restorations. The manufacturers claim that bulk-fill composites have a lower polymerization shrinkage than conventional composites. This study aimed to assess the polymerization shrinkage of five bulk-fill composites in comparison with a conventional composite. MATERIALS AND METHODS: In this in-vitro experimental study, composite discs (n=30) were fabricated using everX Posterior (EXP), Filtek Bulk-Fill Posterior (FBP), SonicFill 2 (SF2), Tetric N-Ceram Bulk-Fill (TNB), X-tra fil (XF), and Filtek Z250 conventional composite at the center of a metal ring bonded to a microscope slide and were covered with a coverslip. This assembly was transferred to a linear variable differential transformer (LVDT). Light-curing (1200 mW/cm2) was performed from underneath the slide for 30 seconds. The deflecting disc method and LVDT were used to assess the dimensional changes of the samples (indicative of polymerization shrinkage) at 1, 30, 60, and 1800 seconds following the onset of light irradiation. Data were analyzed using one-way analysis of variance (ANOVA) and Tukey's test. RESULTS: The groups were significantly different regarding polymerization shrinkage (P<0.002). The polymerization shrinkage of the tested composites following the onset of light irradiation ranged from 0.19 to 3.03. EXP showed a significantly higher polymerization shrinkage than other composites at 30, 60, and 1800 seconds after light irradiation, while XF showed the lowest polymerization shrinkage at the aforementioned time points. CONCLUSIONS: The tested bulk-fill composites had a polymerization shrinkage similar to that of the conventional composite.