Determination of 3‐D Alumina Grain Orientation,Size, Shape,and Growth Kinetics from 2‐D Data in Nextel™ 610 Fibers

Nextel^? 610 alumina fibers were heat‐treated at 1100°C–1500°C for 1–100 h in air. Grain size distributions (GSDs) and grain orientation distributions (ODs) with respect to the fiber axis were characterized by analysis of TEM images from longitudinal fiber sections. The 2‐D GSDs and ODs were characterized as ellipses. 3‐D GSDs and ODs were calculated by fitting distributions of oriented oblate ellipsoids to 2‐D GSDs and ODs formed by ellipsoid–section‐plane intersections. The standard deviations (SDs) of log‐normal GSDs consistently increased with grain size, which is not diagnostic of normal grain growth. The grain aspect ratio (α) and the tendency of the short grain axis to orient perpendicular to the fiber axis also increased with grain size, resulting in more textured fibers at larger grain sizes. Average 3‐D grain sizes were larger than 2‐D sizes for GSDs with small SDs, but smaller for GSDs with large SDs because of under sampling of small grains. 3‐D grain growth kinetics had the same 815 kJ/mol activation energy as that found by 2‐D analysis, but the grain growth exponent m of 6.0 was larger and the pre‐exponential factor much smaller. Expressions for 3‐D log‐normal GSDs as a function of heat treatment temperature and time were determined. α‐distributions and ODs were determined as a function of grain size. Methods for determining 3‐D GSDs are discussed.     

The Involvement of Long Non-Coding RNAs in Bone

A harmonious balance between osteoblast and osteoclast activity guarantees optimal bone formation and resorption, pathological conditions affecting the bone may arise. In recent years, emerging evidence has shown that epigenetic mechanisms play an important role during osteoblastogenesis and osteoclastogenesis processes, including long non-coding RNAs (lncRNAs). These molecules are a class of ncRNAs with lengths exceeding 200 nucleotides not translated into protein, that have attracted the attention of the scientific community as potential biomarkers to use for the future development of novel diagnostic and therapeutic approaches for several pathologies, including bone diseases. This review aims to provide an overview of the lncRNAs and their possible molecular mechanisms in the osteoblastogenesis and osteoclastogenesis processes. The deregulation of their expression profiles in common diseases associated with an altered bone turnover is also described. In perspective, lncRNAs could be considered potential innovative molecular biomarkers to help with earlier diagnosis of bone metabolism-related disorders and for the development of new therapeutic strategies.     

A Sex Perspective in Neurodegenerative Diseases: microRNAs as Possible Peripheral Biomarkers

Sex is a significant variable in the prevalence and incidence of neurological disorders. Sex differences exist in neurodegenerative disorders (NDs), where sex dimorphisms play important roles in the development and progression of Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. In the last few years, some sex specific biomarkers for the identification of NDs have been described and recent studies have suggested that microRNA (miRNA) could be included among these, as influenced by the hormonal and genetic background. Failing to consider the possible differences between males and females in miRNA evaluation could introduce a sex bias in studies by not considering some of these sex-related biomarkers. In this review, we recapitulate what is known about the sex-specific differences in peripheral miRNA levels in neurodegenerative diseases. Several studies have reported sex-linked disparities, and from the literature analysis miR-206 particularly has been shown to have a sex-specific involvement. Hopefully, in the near future, patient stratification will provide important additional clues in diagnosis, prognosis, and tailoring of the best therapeutic approaches for each patient. Sex-specific biomarkers, such as miRNAs, could represent a useful tool for characterizing subgroups of patients.     

Emerging Roles of Exosomes in Huntington’s Disease

Huntington’s disease (HD) is a rare hereditary autosomal dominant neurodegenerative disorder, which is caused by expression of mutant huntingtin protein (mHTT) with an abnormal number of glutamine repeats in its N terminus, and characterized by intracellular mHTT aggregates (inclusions) in the brain. Exosomes are small extracellular vesicles that are secreted generally by all cell types and can be isolated from almost all body fluids such as blood, urine, saliva, and cerebrospinal fluid. Exosomes may participate in the spreading of toxic misfolded proteins across the central nervous system in neurodegenerative diseases. In HD, such propagation of mHTT was observed both in vitro and in vivo. On the other hand, exosomes might carry molecules with neuroprotective effects. In addition, due to their capability to cross blood-brain barrier, exosomes hold great potential as sources of biomarkers available from periphery or carriers of therapeutics into the central nervous system. In this review, we discuss the emerging roles of exosomes in HD pathogenesis, diagnosis, and therapy.     

The role of alpha-dystrobrevin in striated muscle

Muscular dystrophies are a group of diseases that primarily affect striated muscle and are characterized by the progressive loss of muscle strength and integrity. Major forms of muscular dystrophies are caused by the abnormalities of the dystrophin glycoprotein complex (DGC) that plays crucial roles as a structural unit and scaffolds for signaling molecules at the sarcolemma. α-Dystrobrevin is a component of the DGC and directly associates with dystrophin. α-Dystrobrevin also binds to intermediate filaments as well as syntrophin, a modular adaptor protein thought to be involved in signaling. Although no muscular dystrophy has been associated within mutations of the α-dystrobrevin gene, emerging findings suggest potential significance of α-dystrobrevin in striated muscle. This review addresses the functional role of α-dystrobrevin in muscle as well as its possible implication for muscular dystrophy.     

Tear Proteomics Study of Dry Eye Disease: Which Eye Do You Adopt as the Representative Eye for the Study?

Most studies about dry eye disease (DED) chose unilateral eye for investigation and drew conclusions based on monocular results, whereas most studies involving tear proteomics were based on the results of pooling tears from a group of DED patients. Patients with DED were consecutively enrolled for binocular clinical tests, tear biochemical markers of DED, and tear proteome. We found that bilateral eyes of DED patients may have similar but different ocular surface performance and tear proteome. Most ocular surface homeostatic markers and tear biomarkers were not significantly different in the bilateral eyes of DED subjects, and most clinical parameters and tear biomarkers were correlated significantly between bilateral eyes. However, discrepant binocular presentation in the markers of ocular surface homeostasis and the associations with tear proteins suggested that one eye’s performance cannot represent that of the other eye or both eyes. Therefore, in studies for elucidating tear film homeostasis of DED, we may lose some important messages hidden in the fellow eye if we collected clinical and proteomic data only from a unilateral eye. For mechanistic studies, it is recommended that researchers collect tear samples from the eye with more severe DED under sensitive criteria for identifying the more severe eye and evaluating the tear biochemical and proteomic markers with binocular concordance drawn in prior binocular studies.     

Circulating RNA Molecules as Biomarkers in Liver Disease

Liver disease is a major cause of morbidity and mortality worldwide. As in other fields of medicine, there is a stringent need for non-invasive markers to improve patient diagnostics, monitoring and prognostic ability in liver pathology. Cell-free circulating RNA molecules have been recently acknowledged as an important source of potential medical biomarkers. However, many aspects related to the biology of these molecules remain to be elucidated. In this review, we summarize current concepts related to the origin, transportation and possible functions of cell-free RNA. We outline current development of extracellular RNA-based biomarkers in the main forms of non-inherited liver disease: chronic viral hepatitis, hepatocellular carcinoma, non-alcoholic fatty liver, hepato-toxicity, and liver transplantation. Despite recent technological advances, the lack of standardization in the assessment of these markers makes their adoption into clinical practice difficult. We thus finally review the main factors influencing quantification of circulating RNA. These factors should be considered in the reporting and interpretation of current findings, as well as in the proper planning of future studies, to improve reliability and reproducibility of results.     

The Diagnostic Potential of Amyloidogenic Proteins

Neurodegenerative disorders are a highly prevalent class of diseases, whose pathological mechanisms start before the appearance of any clear symptoms. This fact has prompted scientists to search for biomarkers that could aid early treatment. These currently incurable pathologies share the presence of aberrant aggregates called amyloids in the nervous system, which are composed of specific proteins. In this review, we discuss how these proteins, their conformations and modifications could be exploited as biomarkers for diagnostic purposes. We focus on proteins that are associated with the most prevalent neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases, amyotrophic lateral sclerosis, and frontotemporal dementia. We also describe current challenges in detection, the most recent techniques with diagnostic potentials and possible future developments in diagnosis.     

CLA prevents alterations in glycolytic metabolites induced by a high fat diet

CLA has been reported to have beneficial and controversial effects on glucose and lipid metabolism. Besides, high fat (HF) diets induce alterations in liver and muscle lipid deposition, which could be associated with anomalous glucose utilization. Therefore, our aim was to evaluate whether the intake of CLA could prevent alterations in glycolytic intermediate metabolites and glycogen deposition induced by a HF diet. For this purpose, growing mice were fed a control diet (7% corn oil), a HF diet (20% corn oil), or a HF diet containing 17% corn oil + 3% CLA for 30 days. Liver and muscle glucose intermediate metabolites and glycogen were assessed. Liver glycolysis was inhibited by HF, reflected by a decreased flow of substrates through phosphofructokinase‐1α linked to elevated citrate. CLA at HF diet prevented these alterations while increasing the lactate and glycogen synthesis. In the muscle, the HF diet emphasized the reduction of the flux through phosphofructokinase‐1α, without additional changes in total glycogen levels. In conclusion, dietary CLA partially prevented glycolytic pathway alterations in the liver but not in the muscle of mice fed a HF diet, associated with adverse effects as sustained hyperglycemia and hepatic lactate accumulation. Practical applications: The present study evaluates the potential use of CLA and its consequences on several aspects of glucose metabolism. Considering that the FDA has recently approved CLA as a Generally Recognized as Safe (GRAS) category, a measure that will foster the commercial production of food and beverages with CLA supplementation, we believe it is relevant to study its potential functional properties on glucose metabolism in an experimental animal model characterized by alterations in liver and muscle lipid deposition.     

Alcohol-Related Liver Disease: Basic Mechanisms and Clinical Perspectives

Alcohol-related liver disease (ALD) refers to the liver damage occurring due to excessive alcohol consumption and involves a broad spectrum of diseases that includes liver steatosis, steatohepatitis, hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). The progression of ALD is mainly associated with the amount and duration of alcohol usage; however, it is also influenced by genetic, epigenetic, and environmental factors. The definite diagnosis of ALD is based on a liver biopsy, although several non-invasive diagnostic tools and serum biomarkers have emerging roles in the early detection of ALD. While alcohol abstinence and nutritional support remain the cornerstone of ALD treatment, growing evidence has revealed that the therapeutic agents that target oxidative stress or gut-liver axis, inflammatory response inhibition, and liver regeneration enhancement also play a role in ALD management. Furthermore, microRNAs modulation and mesenchymal stem cell-based therapy have emerging potential as ALD therapeutic options. This review summarizes the updated understanding of the pathophysiology, diagnosis, and novel therapeutic approaches for ALD.     

MicroRNAs,Parkinson’s Disease,and Diabetes Mellitus

Parkinson’s disease (PD) is a neurodegenerative disorder that affects 1% of the population over the age of 60. Diabetes Mellitus (DM) is a metabolic disorder that affects approximately 25% of adults over the age of 60. Recent studies showed that DM increases the risk of developing PD. The link between DM and PD has been discussed in the literature in relation to different mechanisms including mitochondrial dysfunction, oxidative stress, and protein aggregation. In this paper, we review the common microRNA (miRNA) biomarkers of both diseases. miRNAs play an important role in cell differentiation, development, the regulation of the cell cycle, and apoptosis. They are also involved in the pathology of many diseases. miRNAs can mediate the insulin pathway and glucose absorption. miRNAs can also regulate PD-related genes. Therefore, exploring the common miRNA biomarkers of both PD and DM can shed a light on how these two diseases are correlated, and targeting miRNAs is a potential therapeutic opportunity for both diseases.     

Extracellular Heat Shock Proteins as Therapeutic Targets and Biomarkers in Fibrosing Interstitial Lung Diseases

Interstitial lung diseases (ILDs) include a large number of diseases and causes with variable outcomes often associated with progressive fibrosis. Although each of the individual fibrosing ILDs are rare, collectively, they affect a considerable number of patients, representing a significant burden of disease. Idiopathic pulmonary fibrosis (IPF) is the typical chronic fibrosing ILD associated with progressive decline in lung. Other fibrosing ILDs are often associated with connective tissues diseases, including rheumatoid arthritis-ILD (RA-ILD) and systemic sclerosis-associated ILD (SSc-ILD), or environmental/drug exposure. Given the vast number of progressive fibrosing ILDs and the disparities in clinical patterns and disease features, the course of these diseases is heterogeneous and cannot accurately be predicted for an individual patient. As a consequence, the discovery of novel biomarkers for these types of diseases is a major clinical challenge. Heat shock proteins (HSPs) are molecular chaperons that have been extensively described to be involved in fibrogenesis. Their extracellular forms (eHSPs) have been recently and successfully used as therapeutic targets or circulating biomarkers in cancer. The current review will describe the role of eHSPs in fibrosing ILDs, highlighting the importance of these particular stress proteins to develop new therapeutic strategies and discover potential biomarkers in these diseases.     

Putative biomarkers and targets of estrogen receptor negative human breast cancer

Breast cancer is a progressive and potentially fatal disease that affects women of all ages. Like all progressive diseases, early and reliable diagnosis is the key for successful treatment and annihilation. Biomarkers serve as indicators of pathological, physiological, or pharmacological processes. Her2/neu, CA15.3, estrogen receptor (ER), progesterone receptor (PR), and cytokeratins are biomarkers that have been approved by the Food and Drug Administration for disease diagnosis, prognosis, and therapy selection. The structural and functional complexity of protein biomarkers and the heterogeneity of the breast cancer pathology present challenges to the scientific community. Here we review estrogen receptor-related putative breast cancer biomarkers, including those of putative breast cancer stem cells, a minor population of estrogen receptor negative tumor cells that retain the stem cell property of self-renewal. We also review a few promising cytoskeleton targets for ER alpha negative breast cancer.     

Biomarkers in Alzheimer’s Disease Analysis by Mass Spectrometry-Based Proteomics

Alzheimer’s disease (AD) is a common chronic and destructive disease. The early diagnosis of AD is difficult, thus the need for clinically applicable biomarkers development is growing rapidly. There are many methods to biomarker discovery and identification. In this review, we aim to summarize Mass spectrometry (MS)-based proteomics studies on AD and discuss thoroughly the methods to identify candidate biomarkers in cerebrospinal fluid (CSF) and blood. This review will also discuss the potential research areas on biomarkers.     

A Review of Microsatellite Markers and Their Applications in Rice Breeding Programs to Improve Blast Disease Resistance

Over the last few decades, the use of molecular markers has played an increasing role in rice breeding and genetics. Of the different types of molecular markers, microsatellites have been utilized most extensively, because they can be readily amplified by PCR and the large amount of allelic variation at each locus. Microsatellites are also known as simple sequence repeats (SSR), and they are typically composed of 1–6 nucleotide repeats. These markers are abundant, distributed throughout the genome and are highly polymorphic compared with other genetic markers, as well as being species-specific and co-dominant. For these reasons, they have become increasingly important genetic markers in rice breeding programs. The evolution of new biotypes of pests and diseases as well as the pressures of climate change pose serious challenges to rice breeders, who would like to increase rice production by introducing resistance to multiple biotic and abiotic stresses. Recent advances in rice genomics have now made it possible to identify and map a number of genes through linkage to existing DNA markers. Among the more noteworthy examples of genes that have been tightly linked to molecular markers in rice are those that confer resistance or tolerance to blast. Therefore, in combination with conventional breeding approaches, marker-assisted selection (MAS) can be used to monitor the presence or lack of these genes in breeding populations. For example, marker-assisted backcross breeding has been used to integrate important genes with significant biological effects into a number of commonly grown rice varieties. The use of cost-effective, finely mapped microsatellite markers and MAS strategies should provide opportunities for breeders to develop high-yield, blast resistance rice cultivars. The aim of this review is to summarize the current knowledge concerning the linkage of microsatellite markers to rice blast resistance genes, as well as to explore the use of MAS in rice breeding programs aimed at improving blast resistance in this species. We also discuss the various advantages, disadvantages and uses of microsatellite markers relative to other molecular marker types.     

Receptor Tyrosine Kinases as Candidate Prognostic Biomarkers and Therapeutic Targets in Meningioma

Meningioma (MGM) is the most common type of intracranial tumor in adults. The validation of novel prognostic biomarkers to better inform tumor stratification and clinical prognosis is urgently needed. Many molecular and cellular alterations have been described in MGM tumors over the past few years, providing a rational basis for the identification of biomarkers and therapeutic targets. The role of receptor tyrosine kinases (RTKs) as oncogenes, including those of the ErbB family of receptors, has been well established in several cancer types. Here, we review histological, molecular, and clinical evidence suggesting that RTKs, including the epidermal growth factor receptor (EGFR, ErbB1), as well as other members of the ErbB family, may be useful as biomarkers and therapeutic targets in MGM.     

Recent Advances in Strategies for Imaging Detection and Intervention of Cellular Senescence

Cellular senescence is a stable cell cycle arrest state that can be triggered by a wide range of intrinsic or extrinsic stresses. Increased burden of senescent cells in various tissues is thought to contribute to aging and age-related diseases. Thus, the detection and interventions of senescent cells are critical for longevity and treatment of disease. However, the highly heterogeneous feature of senescence makes it challenging for precise detection and selective clearance of senescent cells in different age-related diseases. To address this issue, considerable efforts have been devoted to developing senescence-targeting molecular theranostic strategies, based on the potential biomarkers of cellular senescence. Herein, we review recent advances in the field of anti-senescence research and highlight the specific visualization and elimination of senescent cells. Additionally, the challenges in this emerging field are outlined.     

Epithelial-Cell-Derived Extracellular Vesicles in Pathophysiology of Epithelial Injury and Repair in Chronic Rhinosinusitis: Connecting Immunology in Research Lab to Biomarkers in Clinics

Epithelial barrier disruption and failure of epithelial repair by aberrant epithelial-mesenchymal transition (EMT)-induced basal cells observed in nasal mucosa of chronic rhinosinusitis (CRS) are speculated to play important roles in disease pathophysiology. Microparticles (MPs) are a type of extracellular vesicle (EV) released by budding or shedding from the plasma membrane of activated or apoptotic cells. MPs are detected in nasal lavage fluids (NLFs) and are now receiving attention as potential biomarkers to evaluate the degree of activation of immune cells and injury of structural cells in nasal mucosa of subjects with sinus disease. There are three types of epithelial-cell-derived MPs, which are defined by the expression of different epithelial specific markers on their surface: EpCAM, E-cadherin, and integrin β6 (ITGB6). When these markers are on MPs that are also carrying canonical EMT/mesenchymal markers (Snail (SNAI1); Slug (SNAI2); alpha-smooth muscle actin (αSMA, ACTA2)) or pro- and anti-coagulant molecules (tissue factor (TF); tissue plasminogen activator (tPA); plasminogen activator inhibitor-1 (PAI-1)), they provide insight as to the roles of epithelial activation for EMT or regulation of coagulation in the underlying disease. In this review, we discuss the potential of epithelial MPs as research tools to evaluate status of nasal mucosae of CRS patients in the lab, as well as biomarkers for management and treatment of CRS in the clinic.     

Next-Generation Biomarkers in Multiple Myeloma: Understanding the Molecular Basis for Potential Use in Diagnosis and Prognosis

Multiple myeloma (MM) is considered to be the second most common blood malignancy and it is characterized by abnormal proliferation and an accumulation of malignant plasma cells in the bone marrow. Although the currently utilized markers in the diagnosis and assessment of MM are showing promising results, the incidence and mortality rate of the disease are still high. Therefore, exploring and developing better diagnostic or prognostic biomarkers have drawn global interest. In the present review, we highlight some of the recently reported and investigated novel biomarkers that have great potentials as diagnostic and/or prognostic tools in MM. These biomarkers include angiogenic markers, miRNAs as well as proteomic and immunological biomarkers. Moreover, we present some of the advanced methodologies that could be utilized in the early and competent diagnosis of MM. The present review also focuses on understanding the molecular concepts and pathways involved in these biomarkers in order to validate and efficiently utilize them. The present review may also help in identifying areas of improvement for better diagnosis and superior outcomes of MM.     

Peripheral Glycolysis in Neurodegenerative Diseases

Neurodegenerative diseases are a group of nervous system conditions characterised pathologically by the abnormal deposition of protein throughout the brain and spinal cord. One common pathophysiological change seen in all neurodegenerative disease is a change to the metabolic function of nervous system and peripheral cells. Glycolysis is the conversion of glucose to pyruvate or lactate which results in the generation of ATP and has been shown to be abnormal in peripheral cells in Alzheimer’s disease, Parkinson’s disease, and Amyotrophic Lateral Sclerosis. Changes to the glycolytic pathway are seen early in neurodegenerative disease and highlight how in multiple neurodegenerative conditions pathology is not always confined to the nervous system. In this paper, we review the abnormalities described in glycolysis in the three most common neurodegenerative diseases. We show that in all three diseases glycolytic changes are seen in fibroblasts, and red blood cells, and that liver, kidney, muscle and white blood cells have abnormal glycolysis in certain diseases. We highlight there is potential for peripheral glycolysis to be developed into multiple types of disease biomarker, but large-scale bio sampling and deciphering how glycolysis is inherently altered in neurodegenerative disease in multiple patients’ needs to be accomplished first to meet this aim.