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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Construction and evaluation of in-house methylation-sensitive SNaPshot system and three classification prediction models for identifying the tissue origin of body fluid

The identification of tissue origin of body fluid can provide clues and evidence for criminal case investigations.To establish an efficient method for identifying body fluid in forensic cases,eight novel body fluid-specific DNA methylation markers were selected in this study,and a multiplex single base extension reaction(SNaPshot)system for these markers was constructed for the identification of five common body fluids(venous blood,saliva,menstrual blood,vaginal fluid,and semen).The results indicated that the in-house system showed good species specificity,sensitivity,and ability to identify mixed biological samples.At the same time,an artificial body fluid prediction model and two machine learning prediction models based on the support vector machine(SVM)and random forest(RF)algorithms were constructed using previous research data,and these models were validated using the detection data obtained in this study(n=95).The accuracy of the prediction model based on experience was 95.79%;the prediction accuracy of the SVM prediction model was 100.00%for four kinds of body fluids except saliva(96.84%);and the prediction accuracy of the RF prediction model was 100.00%for all five kinds of body fluids.In conclusion,the in-house SNaPshot system and RF prediction model could achieve accurate tissue origin identification of body fluids.

Formation characteristic of Ca-P coatings on magnesium alloy surface

A chemical method was used to deposit dicalcium phosphate dehydrate coatings on AZ91 magnesium alloy. The aim was to improve the biodegradation behavior of magnesium alloy in a simulated body fluid. The microstructures of the coating before and after immersion in the simulated body fluid were characterized by scanning electron microscopy （SEM） and X-ray diffraction （XRD） The results indicated that the dicalcium phosphate dehydrate coatings exhibited two morphologies during the pre-calcification process. The titration speed of the pre-calcification process had great influence on the morphologies of the pre-calcification coatings. As the soaking time increased, the diffraction peaks of dicalcium phosphate dehydrate disappeared and hydroxyapatite precipitated on the coated substrate surfaces. This indicates the dissolution of dicalcium phosphate dehydrate during the immersion process. The structures of the dicalcium phosphate dehydrate coatings and the formation mechanisms of the hydroxyapatite coatings were investigated in detail.

The Inferior Vena Cava Diameter as a Marker of Dry Weight in Chronic Hemodialyzed Patients

We have previously reported that the diameter of the inferior vena cava(IVC) reflects the amount of body fluid in hemodialyzed (HD) patients. The present study was undertaken to depict the criteria of IVC diameters for determining dry weight (DW) in anuric HD patients. In healthy subjects, the maximal diameters during quiet expiration (IVCe) and the minimal diameters during quiet inspiration (IVCi) were (16.7±3.2) and (5.7±5.4)mm,respectively (mean±SD).The collapsibility index (CI,1-IVCi/IVCe), which inversely correlates with the central venous pressure,was 0.68±0.29. In anuric HD patients,the IVCe/CI values before and after HD were 14.9±3.2/0.68±0.24 and 8.2±2.3/0.94±0.09, respectively. IVCe decreased proportionally to the amount of ultrafiltration. In HD patients with hypervolemic pulmonary edema, the IVCe and CI values were 22.4±2.9 and 0.22±0.11, respectively. We proposed that IVCe/CI after HD is (8±3)mm/0.9 ± 0.1 as the markers of DW in anuric HD patients and that an IVCe value≥22mm together with a CI≤0.22 implies the warning level of body fluid retention.

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 .