Diverse Clinical Applications Research Articles

High-Content Drug Discovery Screening of Endocytosis Pathways.

Endocytosis is the dynamic internalization of cargo (receptors, hormones, viruses) for cellular signaling or processing. It involves multiple mechanisms, classified depending on critical proteins involved, speed, morphology of the derived intracellular vesicles, or substance trafficked. Pharmacological targeting of specific endocytosis pathways has a proven utility for diverse clinical applications from epilepsy to cancer. A multiplexable, high-content screening assay has been designed and implemented to assess various forms of endocytic trafficking and the associated impact of potential small molecule modulators. The applications of this assay include (1) drug discovery in the search for specific, cell-permeable endocytosis pathway inhibitors (and associated analogues from structure-activity relationship studies), (2) deciphering the mechanism of internalization for a novel ligand (using pathway-specific inhibitors), (3) assessment of the importance of specific proteins in the trafficking process (using CRISPR-Cas9 technology, siRNA treatment, or transfection), and (4) identifying whether endocytosis inhibition is an off-target for novel compounds designed for alternative purposes. We describe this method in detail and provide a range of troubleshooting options and alternatives to modify the protocol for lab-specific applications.

Platelet Rich Fibrin Membrane Grafting After Laser Excision for Oral Mucosal Lesions.

Platelet rich fibrin (PRF) is a novel surgical biomaterial which has shown immense healing and regenerative potential with diverse clinical applications. Surgical excision is a routinely employed treatment modality for mucosal oral lesions with or without grafting or repair of the base of the wound. We proposed a hypothesis that covering of the base of excised lesion with this platelet rich fibrin membrane can accelerate the rate of physiological healing process and regeneration. To evaluate the role, efficacy, advantages and adverse effects if any, of placement of PRF membrane grafts over surgical excision sites of oral mucosal lesions. Platelet rich fibrin membrane graft was prepared as per recommendation and established protocols. Patients were selected for surgical excision of localized, superficial oral mucosal lesions after meticulous clinical and radiological considerations and informed consent was taken. After laser excision with safe margins, the base of wound was covered with PRF membrane graft, stitched in place by 3-0 vicryl sutures. The operated site was clinically evaluated at regular intervals and a healing score was calculated and statistically tabulated on the basis of various parameters of healing. A total of 34 patients were included in the study with a male preponderance (21 males and 13 females). Satisfactory and clinically acceptable wound healing was observed in most of the patient with minimal morbidities. Surgical site demonstrated good healing score and clinically complete healing with good epithelialisation was achieved in all patients. Platelet rich fibrin membrane is an effective grafting biomaterial after excision of oral mucosal lesions as it enhances the rate of healing with minimal complications. We recommend further multicentre studies with higher sample size to explore its utility and clinical applications in different avenues of oral and head neck surgery.

Marine Algae-PLA composites as de novo alternative to porcine derived collagen membranes

Resorbable and volume-stable collagen matrices have been preferred as grafting materials for diverse clinical applications in recent years. On the other hand, there is always an existing risk of transmission of infection with the cells or the tissues of the graft in using such collagen matrices. Moreover, considering the economic aspects, there is also a need for cost-efficient alternative materials. In this sense, marine algae can be considered as alternatives since they represent vast and cheap source of potential biopolymers. This work covers a comprehensive cytocompatibility study of composite biopolymers derived from different types of marine algae.

A Comprehensive Review on Therapeutic Potential of Benzimidazole: A Miracle Scaffold

Background: Benzimidazole is a category of heterocyclic aromatic compounds formed from the fusion of six membered benzene with five membered imidazolering. The moiety possesses diverse biological and clinical applications. A number of studies have shown that a varied substituent around the benzimidazole nucleus results in pharmacologically active compounds of therapeutic interest. Purpose: Owing to its number of pharmacological properties, this moiety is of choice of interest in designing and synthesis of new therapeutic compounds. The existence of the benzimidazole core in numerous groups of biological agents like antimicrobial, antiviral, antiparasitic, antihypertensive, anticancer, CNS stimulant as well as depressants has made important scaffold for development of many newer therapeutic agents. There is utmost need to understand the synthesis and associated role of benzimidazole derived compounds in different diseases. Therefore, in the present review, we attempt to discuss various derivatives of benzimidazole nucleus with different pharmacological activities. Conclusion: Benzimidazoles have played a great role in discovery of drug and development. Huge attempt has been made towards benzimidazole heterocyclic-based organic compounds with great excellence that resulted in drugs with enormous biological activity. Therapeutic drugs containing benzimidazole nucleus are used in building drugs that serve to be an active area of research. This article becomes a source that will lead to discovery of new opportunities for all researchers interested in benzimidazole-based heterocyclic medicinal chemistry.

Machine and deep learning methods for radiomics.

Radiomics is an emerging area in quantitative image analysis that aims to relate large-scale extracted imaging information to clinical and biological endpoints. The development of quantitative imaging methods along with machine learning has enabled the opportunity to move data science research towards translation for more personalized cancer treatments. Accumulating evidence has indeed demonstrated that noninvasive advanced imaging analytics, that is, radiomics, can reveal key components of tumor phenotype for multiple three-dimensional lesions at multiple time points over and beyond the course of treatment. These developments in the use of CT, PET, US, and MR imaging could augment patient stratification and prognostication buttressing emerging targeted therapeutic approaches. In recent years, deep learning architectures have demonstrated their tremendous potential for image segmentation, reconstruction, recognition, and classification. Many powerful open-source and commercial platforms are currently available to embark in new research areas of radiomics. Quantitative imaging research, however, is complex and key statistical principles should be followed to realize its full potential. The field of radiomics, in particular, requires a renewed focus on optimal study design/reporting practices and standardization of image acquisition, feature calculation, and rigorous statistical analysis for the field to move forward. In this article, the role of machine and deep learning as a major computational vehicle for advanced model building of radiomics-based signatures or classifiers, and diverse clinical applications, working principles, research opportunities, and available computational platforms for radiomics will be reviewed with examples drawn primarily from oncology. We also address issues related to common applications in medical physics, such as standardization, feature extraction, model building, and validation.

Bioprinting on sheet-based scaffolds applied to the creation of implantable tissue-engineered constructs with potentially diverse clinical applications: Tissue-Engineered Muscle Repair (TEMR) as a representative testbed

ABSTRACTPurpose: This report explores the overlooked potential of bioprinting to automate biomanufacturing of simple tissue structures, such as the uniform deposition of (mono)layers of progenitor cells on sheetlike decellularized extracellular matrices (dECM). In this scenario, dECM serves as a biodegradable celldelivery matrix to provide enhanced regenerative microenvironments for tissue repair. The Tissue-Engineered Muscle Repair (TEMR) technology—where muscle progenitor cells are seeded onto a porcine bladder acellular matrix (BAM), serves as a representative testbed for bioprinting applications. Previous work demonstrated that TEMR implantation improved functional outcomes following VML injury in biologically relevant rodent models.Materials and Methods: In the described bioprinting system, a cell-laden hydrogel bioink is used to deposit high cell densities (1.4 × 105-3.5 × 105 cells/cm2), onto both sides of the bladder acellular matrix as proof-of-concept.Results: These bioprinting methods achieve a reproducible and homogeneous distribution of cells, on both sides of the BAM scaffold, after just 24hrs, with cell viability as high as 98%. These preliminary results suggest bioprinting allows for improved dual-sided cell coverage compared to manual-seeding.Conclusions: Bioprinting can enable automated fabrication of TEMR constructs with high fidelity and scalability, while reducing biomanufacturing costs and timelines. Such bioprinting applications are underappreciated, yet critical, to expand the overall biomanufacturing paradigm for tissue engineered medical products. In addition, biofabrication of sheet-like implantable constructs, with cells deposited on both sides, is a process that is both scaffold and cell-type agnostic, and furthermore, is amenable to many geometries, and thus, additional tissue engineering applications beyond skeletal muscle.

Deep learning approaches to biomedical image segmentation

Abstract The review covers automatic segmentation of images by means of deep learning approaches in the area of medical imaging. Current developments in machine learning, particularly related to deep learning, are proving instrumental in identification, and quantification of patterns in the medical images. The pivotal point of these advancements is the essential capability of the deep learning approaches to obtain hierarchical feature representations directly from the images, which in turn is eliminating the need for handcrafted features. Deep learning is expeditiously turning into the state-of-the-art for medical image processing and has resulted in performance improvements in diverse clinical applications. In this review, the basics of deep learning methods are discussed along with an overview of successful implementations involving image segmentation for different medical applications. Finally, some research issues are highlighted and the future need for further improvements is pointed out.

Synthesis and Antibacterial activity of some newer Benzimidazole derivatives

A series of some newer benzimidazole derivatives were synthesized and evaluated for their anti-bacterial activity. Some of new benzimidazole derivatives are derived from the parent compound. The result shows all the compounds have low micromoler minimal inhibitory concentration (MIC) gives a good antibacterial activity against Gram-positive or Gram-negative bacteria. Benzimidazole is the heterocyclic compound formed from benzene ring and five-member ring containing nitrogen and its derivatives are wide interest because of their diverse biological activity and clinical applications.

Reproducibility assessment of neuromelanin-sensitive magnetic resonance imaging protocols for region-of-interest and voxelwise analyses

Neuromelanin-sensitive MRI (NM-MRI) provides a noninvasive measure of the content of neuromelanin (NM), a product of dopamine metabolism that accumulates with age in dopamine neurons of the substantia nigra (SN). NM-MRI has been validated as a measure of both dopamine neuron loss, with applications in neurodegenerative disease, and dopamine function, with applications in psychiatric disease. Furthermore, a voxelwise-analysis approach has been validated to resolve substructures, such as the ventral tegmental area (VTA), within midbrain dopaminergic nuclei thought to have distinct anatomical targets and functional roles. NM-MRI is thus a promising tool that could have diverse research and clinical applications to noninvasively interrogate in vivo the dopamine system in neuropsychiatric illness. Although a test-retest reliability study by Langley et al. using the standard NM-MRI protocol recently reported high reliability, a systematic and comprehensive investigation of the performance of the method for various acquisition parameters and preprocessing methods has not been conducted. In particular, most previous studies used relatively thick MRI slices (~3 ​mm), compared to the typical in-plane resolution (~0.5 ​mm) and to the height of the SN (~15 ​mm), to overcome technical limitations such as specific absorption rate and signal-to-noise ratio, at the cost of partial-volume effects. Here, we evaluated the effect of various acquisition and preprocessing parameters on the strength and test-retest reliability of the NM-MRI signal to determine optimized protocols for both region-of-interest (including whole SN-VTA complex and atlas-defined dopaminergic nuclei) and voxelwise measures. Namely, we determined a combination of parameters that optimizes the strength and reliability of the NM-MRI signal, including acquisition time, slice-thickness, spatial-normalization software, and degree of spatial smoothing. Using a newly developed, detailed acquisition protocol, across two scans separated by 13 days on average, we obtained intra-class correlation values indicating excellent reliability and high contrast, which could be achieved with a different set of parameters depending on the measures of interest and experimental constraints such as acquisition time. Based on this, we provide detailed guidelines covering acquisition through analysis and recommendations for performing NM-MRI experiments with high quality and reproducibility. This work provides a foundation for the optimization and standardization of NM-MRI, a promising MRI approach with growing applications throughout clinical and basic neuroscience.

A robust OFF-ON fluorescent biosensor for detection and clearance of bacterial endotoxin by specific peptide based aggregation induced emission

Endotoxin, also known as lipopolysaccharide (LPS), can induce strong immune response that causes casualties annually. This number may be greatly reduced if specific, robust, sensitive and more capable of clearance LPS biosensor existed. By introducing a LPS specific binding peptide to a typical aggregation induced emission (AIE) fluorophore, 1-(4-carboxylbenzene)-1,2,2-triphenyl (CTPY), a robust, sensitive and specific “OFF-ON” fluorescent biosensor was developed. The biosensor can achieve LPS sensing of a linear relationship in the concentration range of 0.1–1 μM with a detection limit of 6.97 nM. Moreover, a rapid clearance of LPS is simultaneous realized by integration of mesoporous silica nanospheres with a LPS recognition peptide. Such robust biosensor with highly specific detection and rapid clearance based on LPS specific binding peptide hold considerable promise in diverse clinical and biological applications.

Preliminary investigation of a reusable radiochromic sheet for radiation dosimetry

This work investigates a novel reusable radiochromic sheet developed as an economic film substitute or as a radiochromic bolus. The radiation-induced optical density (OD) change of the sheet is read-out with a commercial flat-bed optical scanner. An optimized readout procedure was developed including an optimal scan-time window. Fundamental radiochromic properties of the sheets were characterized including temporal decay of OD, dose sensitivity and consistency through repeated irradiations, and temperature sensitivity. The radiation induced OD change in the sheets was found to decay to baseline within ~24 hours, after which the sheet could be reused. The sensitivity of subsequent re-irradiations was found to be consistent within ±5% (coefficient of variation of 4.5%) for at least 6 irradiations and potentially many more. Importantly, the sheets were not observed to carry any detectable memory of previous irradiations within measurement uncertainty. In conclusion, the Presage sheets show promise as an economic multi-purpose alternative for film applications and potentially as a radiochromic bolus. Further work is required to test the sheet in diverse clinical applications, and to develop a softer material for bolus applications.

Neuromelanin-sensitive MRI as a noninvasive proxy measure of dopamine function in the human brain

Neuromelanin-sensitive MRI (NM-MRI) purports to detect the content of neuromelanin (NM), a product of dopamine metabolism that accumulates with age in dopamine neurons of the substantia nigra (SN). Interindividual variability in dopamine function may result in varying levels of NM accumulation in the SN; however, the ability of NM-MRI to measure dopamine function in nonneurodegenerative conditions has not been established. Here, we validated that NM-MRI signal intensity in postmortem midbrain specimens correlated with regional NM concentration even in the absence of neurodegeneration, a prerequisite for its use as a proxy for dopamine function. We then validated a voxelwise NM-MRI approach with sufficient anatomical sensitivity to resolve SN subregions. Using this approach and a multimodal dataset of molecular PET and fMRI data, we further showed the NM-MRI signal was related to both dopamine release in the dorsal striatum and resting blood flow within the SN. These results suggest that NM-MRI signal in the SN is a proxy for function of dopamine neurons in the nigrostriatal pathway. As a proof of concept for its clinical utility, we show that the NM-MRI signal correlated to severity of psychosis in schizophrenia and individuals at risk for schizophrenia, consistent with the well-established dysfunction of the nigrostriatal pathway in psychosis. Our results indicate that noninvasive NM-MRI is a promising tool that could have diverse research and clinical applications to investigate in vivo the role of dopamine in neuropsychiatric illness.

New approach for brain stimulation

Heart rate variability (HRV) biofeedback is a simple and noninvasive method for brain stimulation. This method includes paced breathing at a rate of about 6 breaths per minute (0.1Hz), which is slower and more rhythmical than natural breathing. HRV biofeedback has been used to successfully treat a wide spectrum of diseases, such as asthma, COPD, IBS, fibromyalgia, hypertension, depression, anxiety, PTSD, and insomnia (Gevirtz, 2013). It has been employed to improve performance in athletes and human operators. Such diverse clinical applications for HRV biofeedback suggest a centrally-mediated mechanism of action. Paced 0.1Hz breathing triggers resonance in the cardiovascular system, thereby eliciting high amplitude oscillations in physiological processes, such as heart rate, blood pressure, stroke volume, and vascular tone. For example, breathing at this frequency maximizes the amplitude of the 0.1Hz oscillation in HR i.e., HR can change from ∼45 to ∼105 bpm during the oscillation period. These resonant oscillations robustly modulate blood flow in the aorta and carotid arteries. We propose that HRV biofeedback stimulates the brain by optimizing brain oxygenation. To test this, fMRI data and ECG were simultaneously collected in 15 college students (18-25 years of age, 13 males) during a 5-minute period of paced 0.1Hz breathing. Blood-Oxygen-Level Dependent (BOLD) signals were recorded in 9 brain regions. High amplitude 0.1Hz peaks were revealed in BOLD frequency spectra of all 9 regions in all participants. Transfer functions were calculated independently for brain regions using HRV as the input and BOLD as the output and revealed a pattern of differential delays in brain responding. The observed delays suggest that the 0.1Hz BOLD wave spreads across the brain regions. We hypothesize that 0.1Hz breathing results in large fluctuations in the diameter of the vessels and, consequently, the level of oxygenation of each brain region.

Direct isolation and characterization of circulating exosomes from biological samples using magnetic nanowires

BackgroundTumor-derived exosomes are gaining attention as important factors that facilitate communication between neighboring cells and manipulate cellular processes associated with cancer development or progression. The conventional techniques for the isolation and detection of exosomes face several limitations, restricting their clinical applications. Hence, a highly efficient technique for the isolation and identification of exosomes from biological samples may provide critical information about exosomes as biomarkers and improve our understanding of their unique role in cancer research. Here, we describe the use of antibody cocktail-conjugated magnetic nanowires to isolate exosomes from plasma of breast and lung cancer patients.MethodsThe isolated exosomes were characterized based on size and concentration using nanoparticle tracking analysis. Levels of exosomal proteins were measured by bicinchoninic acid assay and enzyme-linked immunosorbent assay. Morphology was visualized by transmission electron microscopy. Immunoblotting (Western blotting) was used to detect the presence of exosomal markers.ResultsThe use of antibody cocktail-conjugated magnetic nanowires resulted in approximately threefold greater yield when compared to the conventional methods. The elongated feature of nanowires significantly improved the efficiency of exosome isolation, suggesting its potential to be translated in diverse clinical applications, including cancer diagnosis and treatment.ConclusionsThe nanowire-based method allows rapid isolation of homogeneous population of exosomes with relatively high yield and purity from even small amounts of sample. These results suggest that this method has the potential for clinical applications requiring highly purified exosomes for the analysis of protein, lipid, mRNA, and miRNA.

Accuracy evaluation of tridimensional images performed by portable stereophotogrammetric system

Abstract Introduction Human facial characteristics vary according to individual dental occlusion, facial harmony, orofacial musculature and the format and configuration of craniofacial structures. Traditionally, anthropometric measurements have been acquired through direct evaluation of subjects in a clinical environment using calipers and metric tapes to measure distances between arches and landmarks. Scientific breakthroughs have enabled the digitization of data and introduced the possibility of quick, precise, radiation-free acquisitions; details can be archived for future analysis and easily shared with patients and colleagues. Among new facial analysis methods, the stereophotogrammetry technique has emerged, which uses a group of cameras to take many photographs of a subject in rapid succession from multiple angles. Nowadays, portable stereophotogrammetric systems are being proposed, as they are more practical and easier to use. Objective The aim of this work was to analyze the accuracy and reproducibility of a portable 3D stereophotogrammetric system (Vectra H1, Canfield, Fairfield, NJ, USA) in measuring soft facial tissues of 30 participants, defining measures of a cube and comparing these measurements with those obtained by a set 3D stereophotogrammetric system (Vectra M3, Canfield, Fairfield, NJ, USA) with previously validated accuracy and reproducibility through quantitative analysis of possible errors. Material and method Thirty temporary landmarks were used to measure (in mm) 34 distances in 30 participants (n = 30). Regarding the cube, 12 angles and 9 linear distances were evaluated. Result The results obtained by the established methodology indicated that the Vectra H1 portable system has shown accuracy and reproducibility equal to that of the Vectra M3 set system. Conclusion Data analysis and correlation to literature findings show Vectra H1's capability to reliably capture tridimensional images, which makes it practical for use in diverse clinical applications.

Research and Development of Proteins and Peptides with Therapeutic Potential from Yam Tubers.

We discuss the diverse biological activities, therapeutic potential, and clinical applications of peptides and proteins isolated from various yams species including Dioscorea opposita Thunb (Chinese yam), D alata, D japonica (Japanese yam), D pseudojaponica, D batatas (Korea yam), and D cayenensis. Yam peptides and proteins have many pharmacological activities including immunomodulatory, antioxidant, estrogen-stimulating, osteogenic, angiotensin I-converting enzyme inhibiting, carbonic anhydrase and trypsin inhibiting, chitinase, anti-insect, anti-dust mite, lectin, and anti-proliferative activities. Yam peptides and proteins have therapeutic potential for treating cardiovascular diseases, inflammatory diseases, cancers, aging disorders, menopause, and osteoporosis.

Biocompatibility and Surface Characteristics of Resin-Modified Glass Ionomer Cements with Ammonium Quaternary Compounds or Silver Nanoparticles: AnIn VitroStudy

Glass ionomer cements are materials with diverse clinical applications. Its use is indicated in patients with special needs, pediatric patients, and the elderly; accordingly, it is important to know its properties. The aim of the present study was to determine the cytotoxicity, surface roughness, microhardness, and surface characteristics of GC Fuji ORTHO LC and GC Fuji PLUS resin-modified glass ionomer cements (RMGICs) with 1 and 2% of benzalkonium chloride, cetylpyridinium chloride, hexadecyltrimethylammonium bromide, or silver nanoparticles. All the experimental groups increase or decrease statistically significantly the VHN (P<0.05) compared with the control group, except for GC Fuji PLUS added with hexadecyltrimethylammonium bromide 1 wt%. In the same way, all groups show a statistically significant (P<0.05) increase or decrease in Ra compared with the control group except for GC Fuji ORTHO added with benzalkonium chloride 2 wt%, GC Fuji PLUS added with benzalkonium chloride 2 wt%, and GC Fuji PLUS added with cetylpyridinium chloride 2 wt%. The SEM micrographs show similar surface images between the control and experimental groups. When a dental material is modified, it is important to reevaluate its biological and mechanical characteristics. In the present study, all the additions modified the cytotoxicity and surface characteristics of RMGICs, by increasing or decreasing these properties.

Antibacterial and biodegradable tissue nano-adhesives for rapid wound closure.

BackgroundAlthough various organic tissue adhesives designed to facilitate would healing are gaining popularity in diverse clinical applications, they present significant inherent limitations, such as rejection, infections, toxicity and/or excessive swelling. It is highly desirable to develop efficient, biocompatible and anti-bacterial tissue adhesives for skin wound healing.PurposeInspired by the fact that inorganic nanoparticles can directly glue tissues through the “nanobridging effect”, herein disulfide bond-bridged nanosilver-decorated mesoporous silica nanoparticles (Ag-MSNs) was constructed as an effective and safe tissue adhesive with antibacterial and degradable properties for wound closure and healing.Materials and methodsAg-MSNs was fabricated by controlled reduce of ultrasmall nanosilvers onto the both surface and large pore of biodegradable MSNs. The obtained MSNs were characterized by transmission electron microscopy, Fourier transform infrared spectroscopy, energy-dispersive X-ray spectroscopy, and measurement of size distribution, zeta potential, and mesopore properties. Furthermore, adhesion strength test, anti-bacterial assessment, mouse skin wound model, and MTT assays were used to investigate the tissue adhesive property, antibacterial effect, biodegradability and biocompatibility of the Ag-MSNs.ResultsAg-MSNs exhibited not only strong adhesive properties but also excellent antibacterial activities than that of MSNs. Importantly, this antibacterial nano-adhesive achieved rapid and efficient closure and healing of wounds in comparison to sutures or MSNs in a mouse skin wound model. Furthermore, Ag-MSNs with fast degradable behavior caused little cellular toxicity and even less systemic toxicity during wound healing.ConclusionOur findings suggest that biodegradable Ag-MSNs can be employed as the next generation of nano-adhesives for rapid wound closure and aesthetic wound healing.

MicroRNA Signature of Traumatic Brain Injury: From the Biomarker Discovery to the Point-of-Care.

Traumatic brain injury (TBI) is a serious problem that causes high morbidity and mortality around the world. Currently, no reliable biomarkers are used to assess the severity and predict the recovery. Many protein biomarkers were extensively studied for diagnosis and prognosis of different TBI severities such as S-100β, glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), neurofilament light chain (NFL), cleaved tau protein (C-tau), and ubiquitin C-terminal hydrolase-L1 (UCH-L1). However, none of these candidates is currently used in the clinical practice, due to relatively low sensitivity, for the diagnosis of mild TBI (mTBI) or mild to moderate TBI (MMTBI) patients who are clinically well and do not have a detectable intracranial pathology on the scans. MicroRNAs (miRNAs or miRs) are a class of small endogenous molecular regulators, which showed to be altered in different pathologies, including TBI and for this reason, their potential role in diagnosis, prognosis and therapeutic applications, is explored. Promising miRNAs such as miR-21, miR-16 or let-7i were identified as suitable candidate biomarkers for TBI and can differentiate mild from severe TBI. Also, they might represent new potential therapeutic targets. Identification of miRNA signature in tissue or biofluids, for several pathological conditions, is now possible thanks to the introduction of new high-throughput technologies such as microarray platform, Nanostring technologies or Next Generation Sequencing. This review has the aim to describe the role of microRNA in TBI and to explore the most commonly used techniques to identify microRNA profile. Understanding the strengths and limitations of the different methods can aid in the practical use of miRNA profiling for diverse clinical applications, including the development of a point-of-care device.

Extracellular matrix protein DMP1 suppresses osteogenic differentiation of Mesenchymal Stem Cells

Mesenchymal Stem Cells (MSCs) are self-renewing and multipotent stem cells which was investigated for diverse clinical applications. However, complex mechanism of MSCs fate determination is still not fully disclosed. Extracellular matrix (ECM) proteins contribute to maintain MSCs stemness by providing extracellular microenvironment. Increasing evidences show that ECM proteins could also regulate the fate of MSCs directly. Dentin matrix protein 1 (DMP1) is an ECM protein enrich in bone tissue and terminal cells, which well-known in promoting osteoblasts and osteocytes maturation, and facilitate mineralization. Recently, our experiment indicated that DMP1 was also expressed in MSCs of long bone. In present study, it is found that DMP1 expressed in Prx1 positive MSCs. And, DMP1 is down-regulated in early osteoblasts and up-regulated again in mature osteoblasts. DMP1 conditional knockout mice model under Prx1cre was generated to explore whether DMP1 regulates MSCs osteogenic differentiation. Specific ablation of DMP1 in Prx1 positive MSCs increased bone mass in vivo and promoted osteoblasts activity in vitro. This study provides a new understanding of DMP1's function in regulation of osteogenesis: not only an enhancer of bone formation, but also a negative regulator of MSCs differentiation in bone.