Biomineralization can be considered as nature's strategy to produce and sustain biominerals, primarily via creation of hard tissues for protection and support. This review examines the ...biomineralization process within the hard tissues of the human body with special emphasis on the mechanisms and principles of bone and teeth mineralization. We describe the detailed role of proteins and inorganic ions in mediating the mineralization process. Furthermore, we highlight the various available models for studying bone physiology and mineralization starting from the historical static cell line-based methods to the most advanced 3D culture systems, elucidating the pros and cons of each one of these methods. With respect to the mineralization process in teeth, enamel and dentin mineralization is discussed in detail. The key role of intrinsically disordered proteins in modulating the process of mineralization in enamel and dentine is given attention. Finally, nanotechnological interventions in the area of bone and teeth mineralization, diseases and tissue regeneration is also discussed.
This article provides an overview of the biomineralization process within hard tissues of the human body, which encompasses the detailed mechanism innvolved in the formation of structures like teeth and bone. Moreover, we have discussed various available models used for studying biomineralization and also explored the nanotechnological applications in the field of bone regeneration and dentistry.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Cancer is a major global health issue. It causes extensive individual suffering and gives a huge burden on the health care in society. Despite extensive research and different tools have been ...developed it still remains a challenge for early detection of this disease. FTIR imaging has been used to diagnose and differentiate the molecular differences between normal and diseased tissues.
Fourier Transform Infrared Spectroscopy (FTIR) is able to measure biochemical changes in tissue, cell and biofluids based on the vibrational signature of their components. This technique enables to the distribution and structure of lipids, proteins, nucleic acids as well as other metabolites. These differences depended on the type and the grade of cancer.
We emphasize here, that the FTIR spectroscopy and imaging can be considered as a promising technique and will find its place on the detection of this dreadful disease because of high sensitivity, accuracy and inexpensive technique. Now the medical community started using and accepting this technique for early stage cancer detection. We discussed this technique and the several challenges in its application for the diagnosis of cancer in regards of sample preparations, data interpretation, and data analysis. The sensitivity of chemotherapy drugs on individual specific has also discussed.
So far progressed has done with the FTIR imaging in understanding of cancer disease pathology. However, more research is needed in this field and it is necessary to understand the morphology and biology of the sample before using the spectroscopy and imaging because invaluable information to be figured out.
Neurodegenerative diseases (ND) remains to be one of the biggest burdens on healthcare systems and serves as a leading cause of disability and death. Alzheimer's disease (AD) is among the most common ...of such disorders, followed by Parkinson's disease (PD). The basic molecular details of disease initiation and pathology are still under research. Only recently, the role of exosomes has been linked to the initiation and progression of these neurodegenerative diseases. Exosomes are small bilipid layer enclosed extracellular vesicles, which were once considered as a cellular waste and functionless. These nano-vesicles of 30-150 nm in diameter carry specific proteins, lipids, functional mRNAs, and high amounts of non-coding RNAs (miRNAs, lncRNAs, and circRNAs). As the exosomes content is known to vary as per their originating and recipient cells, these vesicles can be utilized as a diagnostic biomarker for early disease detection. Here we review exosomes, their biogenesis, composition, and role in neurodegenerative diseases. We have also provided details for their characterization through an array of available techniques. Their updated role in neurodegenerative disease pathology is also discussed. Finally, we have shed light on a novel field of salivary exosomes as a potential candidate for early diagnosis in neurodegenerative diseases and compared the biomarkers of salivary exosomes with other blood/cerebrospinal fluid (CSF) based exosomes within these neurological ailments.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Neurodegenerative diseases are a set of progressive and currently incurable diseases that are primarily caused by neuron degeneration. Neurodegenerative diseases often lead to cognitive impairment ...and dyskinesias. It is now well recognized that molecular events precede the onset of clinical symptoms by years. Over the past decade, intensive research attempts have been aimed at the early diagnosis of these diseases. Recently, exosomes have been shown to play a pivotal role in the occurrence and progression of many diseases including cancer and neurodegenerative diseases. Additionally, because exosomes can cross the blood-brain barrier, they may serve as a diagnostic tool for neural dysfunction. In this review, we detail the mechanisms and current challenges of these diseases, briefly review the role of exosomes in the progression of neurodegenerative diseases, and propose a novel strategy based on salivary neuronal exosomes and nanoparticle tracking analysis that could be employed for screening the early onset of neurodegenerative diseases.
We present an electrical sensor that uses rolling circle amplification (RCA) of DNA to stretch across the gap between two electrodes, interact with metal nanoparticle seeds to generate an ...electrically conductive nanowire, and produce electrical signals upon detection of specific target DNA sequences. RCA is a highly specific molecular detection mechanism based on DNA probe circularization. With this technique, long single-stranded DNA with simple repetitive sequences are produced. Here we show that stretched RCA products can be metalized using silver or gold solutions to form metal wires. Upon metallization, the resistance drops from TΩ to kΩ for silver and to Ω for gold. Metallization is seeded by gold nanoparticles aligned along the single-stranded DNA product through hybridization of functionalized oligonucleotides. We show that combining RCA with electrical DNA detection produces results in readout with very high signal-to-noise ratio, an essential feature for sensitive and specific detection assays. Finally, we demonstrate detection of 10 ng of Escherichia coli genomic DNA using the sensor concept.
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IJS, KILJ, NUK, PNG, UL, UM
Autism spectrum disorder (ASD) is considered a complicated neurodevelopment disorder with rising prevalence globally. ASD is characterized by a series of events including varying degrees of defects ...in communication, learning, and social interaction which is accompanied by stereotypical behavioral patterns. Despite extensive research, the current diagnosis for ASD is complex and almost solely based on the behavioral assessments of the suspected individuals. The multifactorial etiopathology of this disease along with the diversity of symptoms among different individuals adds to the current intricacies for accurate prognosis of ASD. Hence, there exists a dire need for biologically relevant biomarkers for an early diagnosis and for tracking the efficacy of therapeutic interventions. Until recently, among various biofluids, saliva has gained increasing interest for biomarker identification, the advantages include the non-invasive nature and ease of sample handling. This mini-review aims to provide a succinct summary of recent literature on saliva-based diagnostic modalities for ASD, examine various studies that highlight the potential use of proteomic and/or RNA-based biomarkers. Finally, some conclusive perspectives of using the salivary system for ASD mechanistic details and diagnosis are also discussed.
Breast cancer, a leading cause of female mortality due to delayed detection owing to asymptomatic nature and limited early diagnostic tools, was investigated using a multi-modal approach. ...Plasma-derived small EVs from breast cancer patients (BrCa, n = 74) and healthy controls (HC, n = 30) were analyzed. Small EVs (n = 104), isolated through chemical precipitation, underwent characterization via transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Validation involved antibody-based tests (TSG101, CD9, CD81, CD63). Infrared spectra of small EVs were obtained, revealing significant differences in lipid acyl chains, particularly in the C-H stretching of CH3. The study focused on the lipid region (3050-2900 cm
), identifying peaks (3015 cm
, 2960 cm
, 2929 cm
) as distinctive lipid characteristics. Spectroscopic lipid-to-lipid ratios (I3015/I2929), (I2960/I2929) emerged as prominent breast cancer markers. Exploration of protein, nucleic acid, and carbohydrate ratios indicated variations in alpha helices, asymmetric C-H stretching vibrations, and C-O stretching at 1033 cm
. Principal component analysis (PCA) successfully differentiated BrCa and HC small EVs, and heatmap analysis and receiver operating characteristic (ROC) curve evaluations underscored the discriminatory power of lipid ratios. Notably, (I2960/I2929) exhibited 100% sensitivity and specificity, highlighting its potential as a robust BrCa sEV marker for breast cancer detection.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Pancreatic Neuroendocrine tumors (PanNET) are challenging to diagnose and often detected at advanced stages due to a lack of specific and sensitive biomarkers. This study utilized proteomics as a ...valuable approach for cancer biomarker discovery; therefore, mass spectrometry-based proteomic profiling was conducted on plasma samples from 12 subjects (3 controls; 5 Grade I, 4 Grade II PanNET patients) to identify potential proteins capable of effectively distinguishing PanNET from healthy controls. Data are available via ProteomeXchange with the identifier PXD045045. 13.2% of proteins were uniquely identified in PanNET, while 60% were commonly expressed in PanNET and controls. 17 proteins exhibiting significant differential expression between PanNET and controls were identified with downstream analysis. Further, 5 proteins (C1QA, COMP, HSP90B1, ITGA2B, and FN1) were selected by pathway analysis and were validated using Western blot analysis. Significant downregulation of C1QA (p = 0.001: within groups, 0.03: control vs. grade I, 0.0013: grade I vs. grade II) and COMP (p = 0.011: within groups, 0.019: control vs grade I) were observed in PanNET Grade I & II than in controls. Subsequently, ELISA on 38 samples revealed significant downregulation of C1QA and COMP with increasing disease severity. This study shows the potential of C1QA and COMP in the early detection of PanNET, highlighting their role in the search for early-stage (Grade-I and Grade-II) diagnostic markers and therapeutic targets for PanNET.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
An acoustic microfluidic system for miniaturized fluorescence-activated cell sorting (μFACS) is presented. By excitation of a miniaturized piezoelectric transducer at 10 MHz in the microfluidic ...channel bottom, an acoustic standing wave is formed in the channel. The acoustic radiation force acting on a density interface causes fluidic movement, and the particles or cells on either side of the fluid interface are displaced in a direction perpendicular to the standing wave direction. The small size of the transducer enables individual manipulation of cells passing the transducer surface. At constant transducer activation the system was shown to accomplish up to 700 μm sideways displacement of 10 μm beads in a 1 mm wide channel. This is much larger than if utilizing the acoustic radiation force acting directly on particles, where the limitation in maximum displacement is between a node and an antinode which at 10 MHz is 35 μm. In the automatic sorting setup, the system was demonstrated to successfully sort single cells of E-GFP expressing β-cells.
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IJS, KILJ, NUK, PNG, UL, UM
Background Alzheimer's disease (AD) is a neurodegenerative disease characterized by Abeta plaques and neurofibrillary tangles. Chronic inflammation and synaptic dysfunction lead to disease ...progression and cognitive decline. Small extracellular vesicles (sEVs) are implicated in AD progression by facilitating the spread of pathological proteins and inflammatory cytokines. This study investigates synaptic dysfunction and neuroinflammation protein markers in plasma-derived sEVs (PsEVs), their association with Amyloid-beta and tau pathologies, and their correlation with AD progression. Methods A total of 90 AD = 35, mild cognitive impairment (MCI) = 25, and healthy age-matched controls (AMC) = 30 participants were recruited. PsEVs were isolated using a chemical precipitation method, and their morphology was characterized by transmission electron microscopy. Using nanoparticle tracking analysis, the size and concentration of PsEVs were determined. Antibody-based validation of PsEVs was done using CD63, CD81, TSG101, and L1CAM antibodies. Synaptic dysfunction and neuroinflammation were evaluated with synaptophysin, TNF-alpha, IL-1beta, and GFAP antibodies. AD-specific markers, amyloid-beta (1-42), and p-Tau were examined within PsEVs using Western blot and ELISA. Results Our findings reveal higher concentrations of PsEVs in AD and MCI compared to AMC (p < 0.0001). Amyloid-beta (1-42) expression within PsEVs is significantly elevated in MCI and AD compared to AMC. We could also differentiate between the amyloid-beta (1-42) expression in AD and MCI. Similarly, PsEVs-derived p-Tau exhibited elevated expression in MCI compared with AMC, which is further increased in AD. Synaptophysin exhibited downregulated expression in PsEVs from MCI to AD (p = 0.047) compared to AMC, whereas IL-1beta, TNF-alpha, and GFAP showed increased expression in MCI and AD compared to AMC. The correlation between the neuropsychological tests and PsEVs-derived proteins (which included markers for synaptic integrity, neuroinflammation, and disease pathology) was also performed in our study. The increased number of PsEVs correlates with disease pathological markers, synaptic dysfunction, and neuroinflammation. Conclusions Elevated PsEVs, upregulated amyloid-beta (1-42), and p-Tau expression show high diagnostic accuracy in AD. The downregulated synaptophysin expression and upregulated neuroinflammatory markers in AD and MCI patients suggest potential synaptic degeneration and neuroinflammation. These findings support the potential of PsEV-associated biomarkers for AD diagnosis and highlight synaptic dysfunction and neuroinflammation in disease progression. Keywords: Alzheimer's disease, Mild cognitive impairment, Small extracellular vesicles, Synaptic dysfunction, Neuroinflammation
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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