Advances and Challenges of Exosome Metabolomics in Body Fluids

Exosomes,ubiquitously present in body fluids,serve as non-invasive biomarkers for disease diagnosis,monitoring,and treatment.As intercellular messengers,exosomes encapsulate a rich array of proteins,nucleic acids,and metabolites,although most studies have primarily focused on proteins and RNA.Recently,exosome metabolomics has demonstrated clinical value and potential advantages in disease detection and pathophysiology,despite significant challenges,particularly in exosome isolation and metabolite detection.This review discusses the significant technical challenges in exosome isolation and metabolite detection,highlighting the advancements in these areas that support the clinical application of exosome metabolomics,and illustrates the potential of exosomal metabolites from various body fluids as biomarkers for early disease diagnosis and treatment.

Critical biomarkers of hepatocellular carcinoma in body fluids and gut microbiota

Hepatocellular carcinoma(HCC)is the most prevalent primary liver cancer and one of the major causes of cancer-related death.The development of specific noninvasive or diagnostic markers from blood,urine and feces may represent a valuable tool for detecting HCC at an early stage.Biomarkers are considered novel potential targets for therapeutic intervention.It helps in the prediction of prognosis or recurrence of HCC,and also assist in the selection of appropriate treatment modality.We summarize the most relevant existing data about various biomarkers that play a key role in the progression of HCC.

Reflections on the Mechanism of Calcium Phosphate Nucleation on Titanium in Simulated Body Fluids

The results and main findings of studies reported in the literature in relation to the deposition of calcium phosphate on Ti in simulated body fluids are summarized. The effects of the surface hydroxyl groups and the sign of surface charge on the nucleation of calcium phosphate are reviewed. One major controversy among the conclusions of different studies is the order of adsorption of the calcium ions and the phosphate ions in the initial stage of immersion. A simple model based on the amphoteric nature of the hydroxyl groups on Ti is proposed in an attempt to delineate the nucleation process for calcium phosphate on Ti in simulated body fluids. HPO4^2- ions interact with the hydroxyl groups via ion exchange and/or electrostatic attraction, and Ca^2＋ ions, via electrostatic attraction only. There is no preferential order of adsorption. Seemingly inconsistent results in different studies possibly arise from different prior treatments of the samples, which affect the adsorption properties.

Identification of Mixtures of Two Types of Body Fluids Using the Multiplex Methylation System and Random Forest Models

Objective Body fluid mixtures are complex biological samples that frequently occur in crime scenes,and can provide important clues for criminal case analysis.DNA methylation assay has been applied in the identification of human body fluids,and has exhibited excellent performance in predicting single-source body fluids.The present study aims to develop a methylation SNaPshot multiplex system for body fluid identification,and accurately predict the mixture samples.In addition,the value of DNA methylation in the prediction of body fluid mixtures was further explored.Methods In the present study,420 samples of body fluid mixtures and 250 samples of single body fluids were tested using an optimized multiplex methylation system.Each kind of body fluid sample presented the specific methylation profiles of the 10 markers.Results Significant differences in methylation levels were observed between the mixtures and single body fluids.For all kinds of mixtures,the Spearman’s correlation analysis revealed a significantly strong correlation between the methylation levels and component proportions(1:20,1:10,1:5,1:1,5:1,10:1 and 20:1).Two random forest classification models were trained for the prediction of mixture types and the prediction of the mixture proportion of 2 components,based on the methylation levels of 10 markers.For the mixture prediction,Model-1 presented outstanding prediction accuracy,which reached up to 99.3%in 427 training samples,and had a remarkable accuracy of 100%in 243 independent test samples.For the mixture proportion prediction,Model-2 demonstrated an excellent accuracy of 98.8%in 252 training samples,and 98.2%in 168 independent test samples.The total prediction accuracy reached 99.3%for body fluid mixtures and 98.6%for the mixture proportions.Conclusion These results indicate the excellent capability and powerful value of the multiplex methylation system in the identification of forensic body fluid mixtures.

α-Synuclein pathology from the body to the brain:so many seeds so close to the central soil

α-Synuclein is a protein that mainly exists in the presynaptic terminals.Abnormal folding and accumulation of α-synuclein are found in several neurodegenerative diseases,including Parkinson’s disease.Aggregated and highly phospho rylated a-synuclein constitutes the main component of Lewy bodies in the brain,the pathological hallmark of Parkinson s disease.For decades,much attention has been focused on the accumulation of α-synuclein in the brain parenchyma rather than considering Parkinson s disease as a systemic disease.Recent evidence demonstrates that,at least in some patients,the initial α-synuclein pathology originates in the peripheral organs and spreads to the brain.Injection of α-synuclein preformed fibrils into the gastrointestinal tra ct trigge rs the gutto-brain propagation of α-synuclein pathology.However,whether α-synuclein pathology can occur spontaneously in peripheral organs independent of exogenous α-synuclein preformed fibrils or pathological α-synuclein leakage from the central nervous system remains under investigation.In this review,we aimed to summarize the role of peripheral α-synuclein pathology in the pathogenesis of Parkinson’s disease.We also discuss the pathways by which α-synuclein pathology spreads from the body to the brain.

Effects of different simulated fluids on anticorrosion biometallic materials

The corrosion behaviors of SUS316L stainless steel, Co Cr alloy and Ti 6Al 4V alloy in Ringer’s, PBS(-) and Hank’s solutions have been investigated. The results indicate that the corrosion of Ringer’s solution is the strongest, then followed by PBS(-) and Hank’s solution. The presence of HPO 2- 4, H 2PO - 4, SO 2- 4 and glucose in the PBS(-)and Hank’s solution probably reduces the corrosion inhibitor and corrosion current. The decrease of the solution’s pH significantly increases the corrosion rate and susceptibility to localized corrosion of SUS316L SS and Co Cr alloy. However, Ti 6Al 4V alloy exhibits an exceptional stability and has only a slight increase of corrosion rate with decreasing pH.

Raman Spectroscopy for Forensic Identification of Body Fluid Traces: Method Validation for Potential False Negatives Caused by Blood-Affecting Diseases

Two critical issues in forensic science are identifying body fluid traces found at crime scenes and preserving them for DNA analysis. However, the majority of current biochemical tests for body fluid identification, which are applicable at the crime scene, are presumptive and destructive to the sample. Raman Spectroscopy provides a suitable alternative to current methods as a nondestructive, confirmatory, and potentially in field method. Our laboratory has developed a chemometric model for the identification of five main body fluids using Raman spectroscopy. This model was developed using samples obtained from healthy donors. Thus, it is of most importance for the forensic application of the method to validate its performance for donors with diseases that might affect the biochemical composition of body fluids. In this study, the developed method was validated using peripheral blood samples acquired from donors with Celiac Disease, Sickle Cell Anemia, and Type 2 Diabetes. It was shown that the method correctly identified all samples as peripheral blood indicating that no false positives could occur because the blood traces were originated from donors suffering from the diseases.

Hydroxyapatite Coatings on Titanium Prepared by Electrodeposition in a Modified Simulated Body Fluid

Hydroxyapatite coatings were directly prepared on anodized titanium by electro-deposition method in a modified simulated body fluid.The configuration,structure and bioactivity of the coating were investigated with scanning electron microscopy(SEM),X-ray diffraction analyzer(XRD)and Fourier transform infrared spectros-copy(FTIR)techniques.The results demonstrated that pure and homogeneous hydroxyapatite coating can be obtained without any post-treatment.The prepared coating showed good bioactivity in simulated body fluid(SBF).The time required for a fully covered dense hydroxyapatite coatings was 4 days immersion in SBF.

Corrosion fatigue of the extruded Mg-Zn-Y-Nd alloy in simulated body fluid

Magnesium alloys were considered to be used as biodegradable implants due to their biocompatibility,biodegradability and nontoxicity.However,under the simultaneous action of corrosive environment and mechanical loading in human body,magnesium alloys are easy to be affected by corrosion fatigue and stress corrosion cracking.In this work,the fatigue behavior of the extruded Mg-Zn-Y-Nd alloy used for vascular stents was studied both in air and in simulated body fluid(SBF).It was revealed that the fatigue limit of as-extruded Mg-Zn-Y-Nd alloy in air is about 65 MPa at 10^7 cycles,while there is no limit in SBF and shows a linear relationship between the fatigue life and stress amplitudes.The fatigue crack source in air was formed by the inclusions and defects.However,the stress corrosion and hydrogen embrittlement are the main reasons for the formation of the fatigue initial crack source in SBF.

Understanding the effects of excimer laser treatment on corrosion behavior of biodegradable Mg-1Ca alloy in simulated body fluid

In this study,a KrF excimer laser was used to modify the biodegradable Mg-1Ca alloy and the time-evolution degradation behavior of the alloy before and after laser treatment was investigated in simulated body fluid(SBF)solution using immersion tests and electrochemical impedance spectroscopy(EIS).A 5μm melted layer with a homogeneous microstructure and an MgO film on the surface were achieved by laser radiation.Corrosion observations(hydrogen evolution,morphology and corrosion products)and EIS results revealed an improvement of corrosion resistance after laser treatment for 48 h.It was found a two-layer structure developed after 2 h immersion on both the untreated and laser-treated alloys,but the sequence of forming the two layers was opposite and greatly influenced by the laser-treated layer.The time-evolution corrosion processes on the untreated and laser-treated alloys were discussed,providing a better understanding of corrosion behavior of biodegradable Mg alloys modified by excimer laser.

Calcium phosphate deposition on surface of porous and dense TiNi alloys in simulated body fluid

Porous and dense TiNi alloys were successfully fabricated by powder metallurgy(P/M) method, and to further improve their surface biocompatibility, surface modification techniques including grind using silicon-carbide(SiC) paper, acid etching and alkali treatment were employed to produce either irregularly rough surface or micro-porous surface roughness. X-ray diffractometry(XRD), scanning electron microscopy(SEM) and energy dispersive X-ray spectroscopy(EDX) attached to SEM were used to characterize surface structure and the Ca-P coatings. Effects of the above surface treatments on the surface morphology, apatite forming ability were systematically investigated. Results indicate that all the above surface treatments increase the apatite forming ability of TiNi alloys in varying degrees when soaked in simulated body fluid(SBF). More apatite coatings formed on TiNi samples sintered at 1050℃ and 1100℃ due to their high porosity and pure TiNi phase that is beneficial to heterogeneous nucleation. Furthermore, more uniform apatite was fabricated on the sample sintered from the mixture of Ni and Ti powders.

Evaluation of Bioactive Properties of α and β Wollastonite Bioceramics Soaked in a Simulated Body Fluid

Dense natural wollastonite bioceramics (CaSiO3) were prepared by a sintering method, varying the pressing load and sintering temperature, in order to obtain different phases of wollastonite, and different physical properties in the materials. The products were characterized by TGA-DTA, XRD, FT-IR, SEM-EDS, TEM and XPS techniques. The results indicate the presence of two polymorphic phases of wollastonite, the β-wollastonite and α-wollastonite with a transition temperature of the β phase to α phase at approximately 1250℃. These materials were soaked in a simulated body fluid (SBF) during 1, 2 and 3 weeks, to study their solubility and bioactivity. The effect of different wollastonite phases on the solubility of Ca and Si, as well as the capacity of producing layers of “newly formed apatite” on the surfaces of these materials in SBF solution were analyzed.

Formation of Apatite in Simulated Body Fluid

It is confirmed that the essential condition for glasses and glass-ceramics to bond to living bone is the formation of an apatite layer on their surfaces in the body.It is proposed that a hydrated silica formed on the surfaces of these materials in the body plays an important role in forming the surface apatite layer,which has not been proved yet.It is shown experimentally that a pure hydrated silica gel can induce the apatite formation on its surface in a simulated body fluid when its starting pH is increased from 7.2 to 7.4.

COMMENTS ON TREATMENT OF OBESITY BASED ON SYNDROME DIFFERENTIATION OF BODY FLUID

Because of no exact name about obesity in traditional Chinese medicine, clinically there have no unified syndrome types about obesity. The present paper uses the original syndrome differentiation of body fluid and selects classical acupuncture and moxibustion prescriptions to treat obesity, which is conducive to further systematizing classical acupuncture and moxibustion prescriptions and providing sufficient basis for clinical popularization.

Body Fluid Changes, Cardiovascular Deconditioning and Metabolic Impairment Are Reversed 24 Hours after a 5-Day Dry Immersion

Dry immersion is an effective and useful model for research in physiology and physiopathology. The focus of this study was to provide integrative insight into renal, endocrine, circulatory, autonomic and metabolic effects of dry immersion. We assessed if the principal changes were restored within 24 h of recovery, and determined which changes were mainly associated with immersion-induced orthostatic intolerance. Five-day dry immersion without countermeasures, and with ad libitum water intake, standardized diet and a permitted short daily rise was performed in a relatively large sample for this experiment type (14 healthy young men). Reduction of total body water derived mostly from extracellular compartment, and stabilized rapidly at the new operating point. Decrease in plasma volume was estimated at 20% - 25%. Five-day immersion was sufficient to impair metabolism with a decrease in glucose tolerance and hypercholesterolemia, but was not associated with pronounced autonomic changes. Five-day immersion induced marked cardiovascular impairment. Immediately after immersion, over half of the subjects were unable to accomplish the 20-min 70° tilt;during tilt, heart rate and total peripheral resistance were increased, and stroke volume was decreased. However, 24 hours of normal physical activity appeared sufficient to reverse orthostatic tolerance and all signs of cardiovascular impairment, and to restitute plasma volume and extracellular fluid volume. Similarly, metabolic impairment was restored. In our study, the major factor responsible for orthostatic intolerance appeared to be hypovolemia. The absence of pronounced autonomic dysfunction might be explained by relatively short duration of dry immersion and daily short-time orthostatic stimulation.

Effect of Ta_(2)O_(5)nanoparticles on bioactivity,composition,structure,in vitro and in vivo behavior of PEO coatings on Mg-alloy

The present study investigates the physical and chemical characteristics,behavior in vitro and in vivo,and biocompatibility of coatings containing Ta_(2)O_(5),which are obtained by plasma electrolytic oxidation(PEO)on MA8 magnesium alloy.The obtained coatings demonstrate in vivo biocompatibility and in vitro bioactivity.Compared to the base PEO coating,the layers containing Ta_(2)O_(5)facilitate the development of apatite in simulated body fluid,suggesting that the inclusion of nanoparticles improves bioactivity of the coatings.It was found that incorporation of Ta_(2)O_(5)nanoparticles increases roughness and porosity of the formed layers by increasing particle concentration in electrolytes for the PEO process contributing to sufficient soft tissue ingrowth in vivo.Based on in vivo studies,these coatings also provide favorable tissue response and minimal inflammatory reaction in comparison with the bare magnesium alloy due to protection of living tissues from deleterious corrosion events of magnesium implant such as local alkalization and intense hydrogen evolution.The results obtained in the present study concluded biocompatibility,tissue integration of the PEO coatings containing Ta_(2)O_(5)nanoparticles making them a promising protective layer for biodegradable magnesium implants.

Gastrin,somatostatin,and experimental disturbance of the gastrointestinal tract in rats

INTRODUCTIONThe field of gastrointestinal hormones has expanded at a dizzying rate[1-4].Gastrointestinal hormones as regulatory peptides that appear to be major components of bodily integration and have important regulatory actions on physioligical function of the gastrointestinal tract .The successful isolation of some gastrointestinal hormones and the development of sensitive methods for their detection have led to the unexpected finding that they also exist in the brain .

Preparation of calcium phosphate coatings on Mg-1.0Ca alloy

The calcium phosphate coatings were prepared by virtue of electrochemical deposition in order to improve the corrosion resistance of Mg-1.0Ca alloys in simulated body fluids.The chemical compositions,structures and morphologies of the coatings were investigated by energy dispersive spectroscopy(EDS),X-ray diffractometry(XRD)and scanning electron microscopy(SEM), respectively.The potentiodynamic electrochemical technique was employed to investigate the bio-degradation behavior of Mg-1.0Ca alloys with Ca-P coatings in Hank's solutions.The experimental results show that the deposited coatings predominately consist of flake-shape brushite(DCPD,CaHPO4·2H2O)crystallites.The corrosion resistance of the substrates with coatings is improved in Hank's solutions significantly.

Investigating Interaction Between Biochanin A and Human Serum Albumin by Multi-spectroscopic and Molecular Simulation Methods

Biochanin A (BCA), the most abundant isoflavone in chickpeas, presents a wide range of biological activities, such as hypolipidaemic, anti-oxidative, anti-proliferative, and estrogen-like effects. We investigated the interaction between BCA and human serum albumin (HSA) via several techniques. UV–Vis absorption spectroscopy verified the conformational variation of HSA after BCA addition, and fluorescence spectroscopy revealed the relevant binding parameters. Circular dichroism spectroscopy was used to estimate the secondary structural changes of HSA with and without BCA. Molecular docking and dynamics simulations were then applied to study the characteristics of HSA with BCA. Energy decomposition analysis was used to prove that Trp214 in subdomain IIA of HSA is the most likely binding site of BCA. Van der Waals forces and hydrophobic interactions may play important roles during the binding process. All of our results showed that BCA presents significant binding affinity to HSA, thus confirming that the role of HSA has as an efficient transporter of biomolecules. © 2017, Tianjin University and Springer-Verlag Berlin Heidelberg.

Effects of geosorbent and solution properties on sorption and desorption of PAHs

Characteristics of phenanthrene and pyrene’s sorption and desorption on two local soils in solutions of simulated groundwater,simulated lung fluid,and simulated saliva were studied with batch equilibrium experiments to understand the fate of PAHs in the karst region of southwestern China and to assess the environmental exposure and the health risk of PAHs.The results showed that the sorption and desorption isotherms of phenanthrene and pyrene on two target soils in the three solution systems could be adequately described by the Freundlich model,while the fitted isotherm parameters for the simulated groundwater solution distinguished notably from those for the simulated body fluid solutions.For the sorption experiments,in the simulated groundwater,the n values were 0.722 and 0.672 for phenanthrene and were 0.724 and0.663 for pyrene,respectively,on the yellow soil and the limestone soil;The log KF values were 3.118 and 3.323 for phenanthrene and were 3.648 and 3.846 for pyrene,respectively,on the yellow soil and the limestone soil.In the simulated body fluids,the n values for phenanthrene and pyrene ranged from 0.622 to 0.836 and from 0.590 to0.865,respectively,and the log KF values of phenanthrene and pyrene ranged from 2.845 to 3.327 and from 3.344 to3.779,respectively.For the desorption experiments,in the simulated groundwater,the n values were 0.662 and 0.744 for phenanthrene and were 0.702 and 0.647 for pyrene,respectively,on the yellow soil and the limestone soil.The log KF values were 3.666 and 3.686 for phenanthrene and were 4.128 and 4.225 for pyrene,respectively,on the yellow soil and the limestone soil.In the simulated body fluids,the n values for phenanthrene and pyrene ranged from 0.612 to 0.668 and from 0.631 to 0.819,respectively,and the log KF values of phenanthrene and pyrene ranged from 3.134 to 3.407 and from 3.533 to 3.839,respectively.The limestone soil had relatively higher log KF values but lower KOC values compared to those of the yellow soil,indicated that the nature of sorbent soils played the dominant role in sorption and desorption behaviors of PAHs.The experimental results showed a remarkable differences in sorption and desorption behaviors of PAHs in simulated body fluids and groundwater.The nonlinearities of measured isotherms and the measured sorption capacities of soils in simulated body fluids were significantly lower than corresponding those in the simulated groundwater,and HI values for simulated body fluids systems were significantly smaller than corresponding those for the simulated groundwater systems.The results underscore cautions in assessing environmental exposure and health risks of PAHs based on their sorption-desorption data in simulated groundwater as this is traditionally done.