Electrochemical biosensors for early diagnosis of glioblastoma.

Glioblastoma (GBM) is a highly aggressive and life-threatening neurological malignancy of predominant astrocyte origin. This type of neoplasm can develop in either the brain or the spine and is also known as glioblastoma multiforme. Although current diagnostic methods such as magnetic resonance imaging (MRI) and positron emission tomography (PET) facilitate tumor location, these approaches are unable to assess disease severity. Furthermore, interpretation of imaging studies requires significant expertise which can have substantial inter-observer variability, thus challenging diagnosis and potentially delaying treatment. In contrast, biosensing systems offer a promising alternative to these traditional approaches. These technologies can continuously monitor specific molecules, providing valuable real-time data on treatment response, and could significantly improve patient outcomes. Among various types of biosensors, electrochemical systems are preferred over other types, as they do not require expensive or complex equipment or procedures and can be made with readily available materials and methods. Moreover, electrochemical biosensors can detect very small amounts of analytes with high accuracy and specificity by using various signal amplification strategies and recognition elements. Considering the advantages of electrochemical biosensors compared to other biosensing methods, we aim to highlight the potential application(s) of these sensors for GBM theranostics. The review's innovative insights are expected to antecede the development of novel biosensors and associated diagnostic platforms, ultimately restructuring GBM detection strategies.

Autophagy and the unfolded protein response shape the non-alcoholic fatty liver landscape: decoding the labyrinth.

The incidence of nonalcoholic fatty liver disease (NAFLD) is on the rise, mirroring a global surge in diabetes and metabolic syndrome, as its major leading causes. NAFLD represents a spectrum of liver disorders, ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), which can potentially progress to cirrhosis and hepatocellular carcinoma (HCC). Mechanistically, we know the unfolded protein response (UPR) as a protective cellular mechanism, being triggered under circumstances of endoplasmic reticulum (ER) stress. The hepatic UPR is turned on in a broad spectrum of liver diseases, including NAFLD. Recent data also defines molecular mechanisms that may underlie the existing correlation between UPR activation and NAFLD. More interestingly, subsequent studies have demonstrated an additional mechanism, i.e. autophagy, to be involved in hepatic steatosis, and thus NAFLD pathogenesis, principally by regulating the insulin sensitivity, hepatocellular injury, innate immunity, fibrosis, and carcinogenesis. All these findings suggest possible mechanistic roles for autophagy in the progression of NAFLD and its complications. Both UPR and autophagy are dynamic and interconnected fluxes that act as protective responses to minimize the harmful effects of hepatic lipid accumulation, as well as the ER stress during NAFLD. The functions of UPR and autophagy in the liver, together with findings of decreased hepatic autophagy in correlation with conditions that predispose to NAFLD, such as obesity and aging, suggest that autophagy and UPR, alone or combined, may be novel therapeutic targets against the disease. In this review, we discuss the current evidence on the interplay between autophagy and the UPR in connection to the NAFLD pathogenesis.

Circular RNAs and cervical cancer: friends or foes? A landscape on circRNA-mediated regulation of key signaling pathways involved in the onset and progression of HPV-related cervical neoplasms.

Cervical cancer (CC) is a common gynecologic malignancy, accounting for a significant proportion of women death worldwide. Human papillomavirus (HPV) infection is one of the major etiological causes leading to CC onset; however, genetic, and epigenetic factors are also responsible for disease expansion. Circular RNAs (circRNAs), which are known as a particular subset of non-coding RNA (ncRNA) superfamily, with covalently closed loop structures, have been reported to be involved in the progression of diverse diseases, especially neoplasms. In this framework, abnormally expressed circRNAs are in strong correlation with CC pathogenesis through regulating substantial signaling pathways. Also, these RNA molecules can be considered as promising biomarkers and therapeutic targets for CC diagnosis/prognosis and treatment, respectively. Herein, we first review key molecular mechanisms, including Wnt/ß-catenin, MAPK, and PI3K/Akt/mTOR signaling pathways, as well as angiogenesis and metastasis, by which circRNAs interfere with CC development. Then, diagnostic, prognostic, and therapeutic potentials of these ncRNA molecules will be highlighted in depth.

Non-coding RNAs in leukemia drug resistance: new perspectives on molecular mechanisms and signaling pathways.

Like almost all cancer types, timely diagnosis is needed for leukemias to be effectively cured. Drug efflux, attenuated drug uptake, altered drug metabolism, and epigenetic alterations are just several of the key mechanisms by which drug resistance develops. All of these mechanisms are orchestrated by up- and downregulators, in which non-coding RNAs (ncRNAs) do not encode specific proteins in most cases; albeit, some of them have been found to exhibit the potential for protein-coding. Notwithstanding, ncRNAs are chiefly known for their contribution to the regulation of physiological processes, as well as the pathological ones, such as cell proliferation, apoptosis, and immune responses. Specifically, in the case of leukemia chemo-resistance, ncRNAs have been recognized to be responsible for modulating the initiation and progression of drug resistance. Herein, we comprehensively reviewed the role of ncRNAs, specifically its effect on molecular mechanisms and signaling pathways, in the development of leukemia drug resistance.

Liver Disorders Caused by Inborn Errors of Metabolism.

Inborn errors of metabolism (IEMs) are a vast array of inherited/congenital disorders, affecting a wide variety of metabolic pathways and/or biochemical processes inside the cells. Although IEMs are usually rare, they can be represented as serious health problems. During the neonatal period, these inherited defects can give rise to almost all key signs of liver malfunction, including jaundice, coagulopathy, hepato- and splenomegaly, ascites, etc. Since the liver is a vital organ with multiple synthetic, metabolic, and excretory functions, IEM-related hepatic dysfunction could seriously be considered life-threatening. In this context, the identification of those hepatic manifestations and their associated characteristics may promote the differential diagnosis of IEMs immediately after birth, making therapeutic strategies more successful in preventing the occurrence of subsequent events. Among all possible liver defects caused by IEMs, cholestatic jaundice, hepatosplenomegaly, and liver failure have been shown to be manifested more frequently. Therefore, the current study aims to review substantial IEMs that mostly result in the aforementioned hepatic disorders, relying on clinical principles, especially through the first years of life. In this article, a group of uncommon hepatic manifestations linked to IEMs is also discussed in brief.

Associations between the circumstances and severity of head impacts in men's university ice hockey.

Improved evidence on the most common and severe types of head impacts in ice hockey can guide efforts to preserve brain health through improvements in protective gear, rink design, player training, and rules of play. In this observational cohort study of men's university hockey, we compared video evidence on the circumstances of 234 head impacts to measures of head impact severity (peak linear accelerations and rotational velocities) from helmet-mounted sensors (GForceTracker). Videos were analyzed with a validated questionnaire, and paired with helmet sensor data. Shoulder-to-head impacts were more common than hand- or elbow-, but there were no differences in head impact severity between upper limb contact sites (p ≥ 0.2). Head-to-glass impacts were nearly four times more common, and just as severe as head-to-board impacts (p ≥ 0.4). Head impacts resulting in major penalties (versus no penalty), or visible signs of concussion (versus no signs), involved greater head rotational velocities (p = 0.038 and 0.049, respectively). Head impacts occurred most often to the side of the head, along the boards to players in their offensive zone without puck possession. Head impact severity did not differ between cases where the head was (versus was not) the primary site of contact (p ≥ 0.6). Furthermore, penalties were called in only 4% of cases where the head was the initial point of contact. Accordingly, rules that focus on primary targeting of the head, while important and in need of improved enforcement, offer a limited solution.

The crosstalk between ubiquitin-conjugating enzyme E2Q1 and p53 in colorectal cancer: An in vitro analysis.

Colorectal cancer (CRC) is a prevalent gastrointestinal neoplasm that ranks fourth in terms of cancer-related deaths worldwide. In the process of CRC progression, multiple ubiquitin-conjugating enzymes (E2s) are involved; UBE2Q1 is one of those newly identified E2s that is markedly expressed in human colorectal tumors. Since p53 is a well-known tumor suppressor and defined as a key factor to be targeted by the ubiquitin-proteasome system, we hypothesized that UBE2Q1 might contribute to CRC progression through the modulation of p53. Using the lipofection method, the cultured SW480 and LS180 cells were transfected with the UBE2Q1 ORF-containing pCMV6-AN-GFP vector. Then, quantitative RT-PCR was used to assay the mRNA expression levels of p53's target genes, i.e., Mdm2, Bcl2, and Cyclin E. Moreover, Western blot analysis was performed to confirm the cellular overexpression of UBE2Q1 and assess the protein levels of p53, pre- and post-transfection. The expression of p53's target genes were cell line-dependent except for Mdm2 that was consistent with the findings of p53. The results of Western blotting demonstrated that the protein levels of p53 were greatly lower in UBE2Q1-transfected SW480 cells compared to the control SW480 cells. However, the reduced levels of p53 protein were not remarkable in the transfected LS180 cells compared to the control cells. The suppression of p53 is believed to be the result of UBE2Q1-dependent ubiquitination and its subsequent proteasomal degradation. Furthermore, the ubiquitination of p53 can act as a signal for degradation-independent functions, such as nuclear export and suppressing the p53's transcriptional activities. In this context, the decreased Mdm2 levels can moderate the proteasome-independent mono-ubiquitination of p53. The ubiquitinated p53 modulates the transcriptional levels of target genes. Therefore, the up-modulation of UBE2Q1 may influence the transcriptional activities depending on p53, and thereby contributes to CRC progression through regulating the p53.

Bilirubin, an endogenous antioxidant that affects p53 protein and its downstream apoptosis/autophagy-related genes in LS180 and SW480 cell culture models of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the commonest neoplasms worldwide, which its pathogenesis is strongly correlated with p53 mutations. Antioxidants are believed to decelerate the CRC progression, possibly through interfering with p53 and its downstream target genes and mechanisms. Regarding the potential antioxidant effects of bilirubin, as an incredible endogenous antioxidant, we sought to investigate how bilirubin affected the expression levels of p53 protein and its downstream target genes, including Mdm2, Bcl-2, BECN1 and LC3, in LS180 and SW480 cell culture models of CRC. METHODS AND RESULTS: Using the MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazolium bromide) assay, 50 and 100 µM concentrations of bilirubin were determined to be non-toxic for both LS180 and SW480 cell lines. Western blot analysis was employed to evaluate the protein expression levels of p53. The results revealed that p53 protein levels were higher in LS180 cells treated with bilirubin compared to the control group. Notwithstanding, in SW480 cells, no considerable changes were observed in p53 protein levels of treated cells compared to the control ones. The quantitative reverse transcriptase-polymerase chain reaction (q RT-PCR) method was used to measure the mRNA expression levels of the apoptosis/autophagy-related genes, Mdm2, Bcl-2, BECN1, and LC3 , as the p53's downstream target genes. Consequently, the expression of Bcl-2 and Mdm2 genes were affected by p53, while BECN1 and LC3 expression levels were decreased in both cell lines. CONCLUSION: Bilirubin is an endogenous antioxidant with significant anti-tumor effects in the studied CRC cell lines, probably through the regulation of p53 protein expression levels and subsequent control of apoptosis and autophagy, as two key processes involved in cell survival and progression of tumor cells.

The landscape of exosomal non-coding RNAs in breast cancer drug resistance, focusing on underlying molecular mechanisms.

Breast cancer (BC) is the most common malignancy among women worldwide. Like many other cancers, BC therapy is challenging and sometimes frustrating. In spite of the various therapeutic modalities applied to treat the cancer, drug resistance, also known as, chemoresistance, is very common in almost all BCs. Undesirably, a breast tumor might be resistant to different curative approaches (e.g., chemo- and immunotherapy) at the same period of time. Exosomes, as double membrane-bound extracellular vesicles 1) secreted from different cell species, can considerably transfer cell products and components through the bloodstream. In this context, non-coding RNAs (ncRNAs), including miRNAs, long ncRNAs (lncRNAs), and circular RNAs (circRNAs), are a chief group of exosomal constituents with amazing abilities to regulate the underlying pathogenic mechanisms of BC, such as cell proliferation, angiogenesis, invasion, metastasis, migration, and particularly drug resistance. Thereby, exosomal ncRNAs can be considered potential mediators of BC progression and drug resistance. Moreover, as the corresponding exosomal ncRNAs circulate in the bloodstream and are found in different body fluids, they can serve as foremost prognostic/diagnostic biomarkers. The current study aims to comprehensively review the most recent findings on BC-related molecular mechanisms and signaling pathways affected by exosomal miRNAs, lncRNAs, and circRNAs, with a focus on drug resistance. Also, the potential of the same exosomal ncRNAs in the diagnosis and prognosis of BC will be discussed in detail.

Circular RNAs: pivotal role in the leukemogenesis and novel indicators for the diagnosis and prognosis of acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aggressive hematological malignancy and affected patients have poor overall survival (OS) rates. Circular RNAs (circRNAs) are a novel class of non-coding RNAs (ncRNAs) with a unique loop structure. In recent years, with the development of high-throughput RNA sequencing, many circRNAs have been identified exhibiting either up-regulation or down-regulation in AML patients compared with healthy controls. Recent studies have reported that circRNAs regulate leukemia cell proliferation, stemness, and apoptosis, both positively and negatively. Additionally, circRNAs could be promising biomarkers and therapeutic targets in AML. In this study, we present a comprehensive review of the regulatory roles and potentials of a number of dysregulated circRNAs in AML.

Bilirubin improves renal function by reversing the endoplasmic reticulum stress and inflammation in the kidneys of type 2 diabetic rats fed high-fat diet.

Diabetic kidney disease (DKD), as a chronic diabetes-induced complication, is considered the most frequent leading cause of end-stage renal disease (ESRD). Regarding the observed protective effects of bilirubin, as a potential endogenous antioxidant/anti-inflammatory compound, against DKD progression, we planned to evaluate the effects of bilirubin administration on endoplasmic reticulum (ER) stress and inflammation in type 2 diabetic (T2D) rats fed high-fat diet (HFD). In this regard, thirty 8-week adult male Sprague Dawley rats were divided into five groups (n = 6). T2D and obesity were induced by streptozotocin (STZ) (35 mg/kg) and HFD (700 kcal/day), respectively. Bilirubin treatment was carried out for 6- and 14-week intervals (10 mg/kg/day), intraperitoneally. Then, the expression levels of ER stress-related genes (i.e. binding immunoglobulin protein (Bip), C/EBP homologous protein (Chop), and spliced x-box-binding protein 1 (sXbp1), as well as nuclear factor-κB (NF-κB) were analyzed using quantitative Real-time PCR experiments. Moreover, histopathological and stereological changes of kidney and its related structures were investigated for the studied rats. Bip, Chop, and NF-κB expression levels were significantly decreased under bilirubin treatment, while sXbp1 was up-regulated following the bilirubin administration. More interestingly, glomerular constructive damages seen in HFD-T2D rats, were considerably improved in the animals received bilirubin. Stereological assessments also revealed that bilirubin could desirably reverse the mitigation of kidney's total volume and its related structures, such as cortex, glomeruli, and convoluted tubules. Taken together, bilirubin has potential protective/ameliorative effects on DKD progression, especially through alleviating the renal ER stress and inflammatory responses in T2D rats with injured kidneys. In this era, clinical benefits of mild hyperbilirubinemia can be considered in human DKD.

Ameliorative effects of bilirubin on cell culture model of non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is defined as the most prevalent hepatic disorder that affects a significant population worldwide. There are several genes/proteins, involving in the modulation of NAFLD pathogenesis; sirtuin1 (SIRT1), TP53-inducible regulator gene (TIGAR), and autophagy-related gene 5 (Atg5) are considered a chief group of these modulators that principally act by regulating the hepatic lipid metabolism, as well as preventing the lipid accumulation. Surprisingly, bilirubin, especially in its unconjugated form, might be able to alleviate NAFLD progression by decreasing lipid accumulation and regulating the expression levels of the above-stated genes. METHODS AND RESULTS: Herein, the interactions between bilirubin and the corresponding genes' products were first analyzed by docking assessments. Afterwards, HepG2 cells were cultured under the optimum conditions, and then were incubated with high concentrations of glucose to induce NAFLD. After treating normal and fatty liver cells with particular bilirubin concentrations for 24- and 48-hour periods, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay, colorimetric method, and quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) were employed to assess cell viability status, intracellular triglycerides content, and mRNA expression levels of the genes, respectively. Intracellular lipid accumulation of HepG2 cells was significantly decreased after treating with bilirubin. Bilirubin also increased SIRT1 and Atg5 gene expression levels in fatty liver cells. TIGAR gene expression levels were variable upon the conditions and the cell type, suggesting a dual role for TIGAR during the NAFLD pathogenesis. CONCLUSION: Our findings indicate the potential of bilirubin in the prevention from or amelioration of NAFLD through influencing SIRT1-related deacetylation and the process of lipophagy, as well as decreasing the intrahepatic lipid content. In vitro model of NAFLD was treated with unconjugated bilirubin under the optimal conditions.Desirably, bilirubin moderated the accumulation of triglycerides within the cells possibly through modulation of the expression of SIRT1, Atg5, and TIGAR genes. In the context, bilirubin was shown to increase the expression levels of SIRT1 and Atg5, while the expression of TIGAR was demonstrated to be either increased or decreased, depending on the treatment conditions. Created with BioRender.com.

The Effects of Statins on Respiratory Symptoms and Pulmonary Fibrosis in COVID-19 Patients with Diabetes Mellitus: A Longitudinal Multicenter Study.

The aim of this prospective cohort study was to explore the effect of statins on long-term respiratory symptoms and pulmonary fibrosis in coronavirus disease 2019 (COVID-19) patients with diabetes mellitus (DM). Patients were recruited from three tertiary hospitals, categorized into Statin or Non-statin groups, and assessed on days 0, 28, and 90 after symptoms onset to record the duration of symptoms. Pulmonary fibrosis was scored at baseline and follow-up time points by high-resolution computed tomography scans. Each group comprised 176 patients after propensity score matching. Data analysis revealed that the odds of having cough and dyspnea were significantly higher in the Non-statin group compared to the Statin group during the follow-up period. Overall, there was no significant difference in the change in pulmonary fibrosis score between groups. However, Non-statin patients with > 5 years of DM were more likely to exhibit a significantly higher fibrosis score during the follow-up period as compared to their peers in the Statin group. Our results suggest that the use of statins is associated with a lower risk of developing chronic cough and dyspnea in diabetic patients with COVID-19, and may reduce pulmonary fibrosis associated with COVID-19 in patients with long-term (> 5 years) DM.

A review of highly sensitive electrochemical genosensors for microRNA detection: A novel diagnostic platform for neurodegenerative diseases diagnostics.

The significant role of microRNAs in regulating gene expression and in disease tracking has handed the possibility of robust and accurate diagnosis of various diseases. Measurement of these biomarkers has also had a significant impact on the preparation of natural samples. Discovery of miRNAs is a major challenge due to their small size in the real sample and their short length, which is generally measured by complex and expensive methods. Electrochemical nanobiosensors have made significant progress in this field. Due to the delicate nature of nerve tissue repair and the significance of rapid-fire feature of neurodegenerative conditions, these biosensors can be reliably promising. This review presents advances in the field of neurodegenerative diseases diagnostics. At the same time, there are still numerous openings in this field that are a bright prospect for researchers in the rapid-fire opinion of neurological diseases and indeed nerve tissue repair.

Recent insights into the roles of circular RNAs in human brain development and neurologic diseases.

Circular RNAs (circRNAs) are a novel class of non-coding RNAs. They are single-stranded RNA transcripts characterized with a closed loop structure making them resistant to degrading enzymes. Recently, circRNAs have been suggested with regulatory roles in gene expression involved in controlling various biological processes. Notably, they have demonstrated abundance, dynamic expression, back-splicing events, and spatiotemporally regulation in the human brain. Accordingly, they are expected to be involved in brain functions and related diseases. Studies in animals and human brain have revealed differential expression of circRNAs in brain compartments. Interestingly, contributing roles of circRNAs in the regulation of central nervous system (CNS) development have been demonstrated in a number of studies. It has been proposed that circRNAs play role in substantial neurological functions like neurotransmitter-associated tasks, neural cells maturation, and functions of synapses. Furthermore, 3 main pathways have been identified in association with circRNAs's host genes including axon guidance, Wnt signaling, and transforming growth factor beta (TGF-ß) signaling pathways, which are known to be involved in substantial functions like migration and differentiation of neurons and specification of axons, and thus play role in brain development. In this review, we have an overview to the biogenesis, biological functions of circRNAs, and particularly their roles in human brain development and the pathogenesis of neurodegenerative diseases including Alzheimer's diseases, multiple sclerosis, Parkinson's disease and brain tumors.

Review of electrochemical and optical biosensors for testosterone measurement.

Testosterone is an anabolic steroid and a major sex hormone in males. It plays vital roles, including developing the testis, penis, and prostate, increasing muscle and bone, and sperm production. In both men and women, testosterone levels should be in normal ranges. Besides, testosterone and its analogs are major global contributors to doping in sport. Due to the importance of testosterone testing, novel, accurate biosensors have been developed. This review summarizes the various methods for testosterone measurement. Also, recent optical and electrochemical approaches for the detection of testosterone and its analogs have been discussed.

Possible Mechanisms and Molecular Signaling of Incretins against the Development of Type 2 Diabetes Mellitus.

The increasing number of cases of diabetes mellitus (DM) and related diseases has become a global health concern. In this context, controlling blood glucose levels is critical to prevent and/or slow down the development of diabetes-related complications. Incretins, as gutderived hormones that trigger the post-meal secretion of insulin, are a well-known family of blood glucose modulators. Currently, incretin medications, including glucagon-like peptide-1 receptor agonist (GLP-1RA) and dipeptidyl peptidase-4 (DPP-4) inhibitors, are extensively used to treat patients with type 2 diabetes mellitus (T2D). Several experimental and clinical studies illustrate that these metabolic hormones exert their antidiabetic effects through multiple molecular mechanisms. Accordingly, the current review aims to investigate key mechanisms and signaling pathways, such as the cAMP/PKA, Nrf2, PI3K/Akt, and AMPK pathways, associated with the antidiabetic effects of incretins. It also summarizes the outcomes of a group of clinical trials evaluating the incretins' antidiabetic potential in diabetic patients.

Exosomal noncoding RNAs in prostate cancer.

Prostate cancer (PCa) is the second most common cancer and the fifth leading cause of mortality among men. The recurrent reports of false-positive results of common PCa biomarkers have led to the introduction of some promising biomarkers for PCa, such as exosomal non-coding RNAs (ncRNAs). Exosomes contain various components, such as several ncRNAs (miRNAs and lncRNAs), which are important in the initiation and progression of PCa. These ncRNAs also reflect the state of the origin cell. In this article, we reviewed research on the importance and roles of ncRNAs in PCa, focusing on exosomal ncRNAs. We highlighted plasma exosomal miRNAs (8 miRNAs), urine exosomal miRNAs (19miRNAs), serum miRNAs (2 miRNAs), and five miRNAs in semen used for PCa diagnosis. Also, four exosomal lncRNAs in plasma and urine can be used as biomarkers for PCa diagnosis.

Epigenetic regulation of autophagy in gastrointestinal cancers.

The development of novel therapeutic approaches is necessary to manage gastrointestinal cancers (GICs). Considering the effective molecular mechanisms involved in tumor growth, the therapeutic response is pivotal in this process. Autophagy is a highly conserved catabolic process that acts as a double-edged sword in tumorigenesis and tumor inhibition in a context-dependent manner. Depending on the stage of malignancy and cellular origin of the tumor, autophagy might result in cancer cell survival or death during the GICs' progression. Moreover, autophagy can prevent the progression of GIC in the early stages but leads to chemoresistance in advanced stages. Therefore, targeting specific arms of autophagy could be a promising strategy in the prevention of chemoresistance and treatment of GIC. It has been revealed that autophagy is a cytoplasmic event that is subject to transcriptional and epigenetic regulation inside the nucleus. The effect of epigenetic regulation (including DNA methylation, histone modification, and expression of non-coding RNAs (ncRNAs) in cellular fate is still not completely understood. Recent findings have indicated that epigenetic alterations can modify several genes and modulators, eventually leading to inhibition or promotion of autophagy in different cancer stages, and mediating chemoresistance or chemosensitivity. The current review focuses on the links between autophagy and epigenetics in GICs and discusses: 1) How autophagy and epigenetics are linked in GICs, by considering different epigenetic mechanisms; 2) how epigenetics may be involved in the alteration of cancer-related phenotypes, including cell proliferation, invasion, and migration; and 3) how epidrugs modulate autophagy in GICs to overcome chemoresistance.

Circular RNAs in Alzheimer's Disease: A New Perspective of Diagnostic and Therapeutic Targets.

BACKGROUND: Circular RNAs (circRNAs), as covalently closed single-stranded noncoding RNA molecules, have been recently identified to involve in several biological processes, principally through targeting microRNAs. Among various neurodegenerative diseases (NDs), accumulating evidence has proposed key roles for circRNAs in the pathogenesis of Alzheimer's disease (AD); although the exact relationship between these RNA molecules and AD progression is not clear, they have been believed to mostly act as miRNA sponges or gene transcription modulators through correlating with multiple proteins, involved in the accumulation of Amyloid ß (Aß) peptides, as well as tau protein, as AD's pathological hallmark. More interestingly, circRNAs have also been reported to play diagnostic and therapeutic roles during AD progression. OBJECTIVE: Literature review indicated that circRNAs could essentially contribute to the onset and development of AD. Thus, in the current review, the circRNAs' biogenesis and functions are addressed at first, and then the interplay between particular circRNAs and AD is comprehensively discussed. Eventually, the diagnostic and therapeutic significance of these noncoding RNAs is highlighted in brief. RESULTS: A large number of circRNAs are expressed in the brain. Thereby, these RNA molecules are noticed as potential regulators of neural functions in healthy circumstances, as well as neurological disorders. Moreover, circRNAs have also been reported to have potential diagnostic and therapeutic capacities in relation to AD, the most prevalent ND. CONCLUSION: CircRNAs have been shown to act as sponges for miRNAs, thereby regulating the function of related miRNAs, including oxidative stress, reduction of neuroinflammation, and the formation and metabolism of Aß, all of which developed in AD. CircRNAs have also been proposed as biomarkers that have potential diagnostic capacities in AD. Despite these characteristics, the use of circRNAs as therapeutic targets and promising diagnostic biomarkers will require further investigation and characterization of the function of these RNA molecules in AD.