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Nanoscale preparations, such as nanoparticles, micelles, and liposomes, are increasingly recognized in pharmaceutical technology for their high capability in tailoring the pharmacokinetics of the encapsulated drug within the body. These preparations have great potential in extending drug half-life, reducing dosing frequency, mitigating drug side effects, and enhancing drug efficacy. Consequently, nanoscale preparations offer promising prospects for the treatment of metabolic disorders, malignant tumors, and various chronic diseases. Nevertheless, the complete clinical potential of nanoscale preparations remains untapped due to the challenges associated with low drug loading degrees and insufficient control over drug release. In this review, we comprehensively summarize the vital role of intermolecular interactions in enhancing encapsulation and controlling drug release within nanoscale delivery systems. Our analysis critically evaluates the characteristics of common intermolecular interactions and elucidates the techniques employed to assess them. Moreover, we highlight the significant potential of intermolecular interactions in clinical translation, particularly in the screening and optimization of preparation prescriptions. By attaining a deeper understanding of intermolecular interaction properties and mechanisms, we can adopt a more rational approach to designing drug carriers, leading to substantial advancements in the application and clinical transformation of nanoscale preparations. Moving forward, continued research in this field offers exciting prospects for unlocking the full clinical potential of nanoscale preparations and revolutionizing the field of drug delivery. [ABSTRACT FROM AUTHOR]

Post-acute sequelae of COVID-19 can present as multi-organ pathology, with neuropsychiatric symptoms being the most common symptom complex, characterizing long COVID as a syndrome with a significant disease burden for affected individuals. Several typical symptoms of long COVID, such as fatigue, depressive symptoms and cognitive impairment, are also key features of other psychiatric disorders such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and major depressive disorder (MDD). However, clinically successful treatment strategies are still lacking and are often inspired by treatment options for diseases with similar clinical presentations, such as ME/CFS. Acetylcarnitine, the shortest metabolite of a class of fatty acid metabolites called acylcarnitines and one of the most abundant blood metabolites in humans can be used as a dietary/nutritional supplement with proven clinical efficacy in the treatment of MDD, ME/CFS and other neuropsychiatric disorders. Basic research in recent decades has established acylcarnitines in general, and acetylcarnitine in particular, as important regulators and indicators of mitochondrial function and other physiological processes such as neuroinflammation and energy production pathways. In this review, we will compare the clinical basis of neuropsychiatric long COVID with other fatigue-associated diseases. We will also review common molecular disease mechanisms associated with altered acetylcarnitine metabolism and the potential of acetylcarnitine to interfere with these as a therapeutic agent. Finally, we will review the current evidence for acetylcarnitine as a supplement in the treatment of fatigue-associated diseases and propose future research strategies to investigate the potential of acetylcarnitine as a treatment option for long COVID. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) accounts for around 90% of all oral cancers and is the eighth most common cancer worldwide. Despite progress in managing OSCC, the overall prognosis remains poor, with a survival rate of around 50–60%, largely due to tumor size and recurrence. The challenges of late-stage diagnosis and limitations in current methods emphasize the urgent need for less invasive techniques to enable early detection and treatment, crucial for improving outcomes in this aggressive form of oral cancer. Research is currently aimed at unraveling tumor-specific metabolite profiles to identify candidate biomarkers as well as discover underlying pathways involved in the onset and progression of cancer that could be used as new targets for diagnostic and therapeutic purposes. Metabolomics is an advanced technological approach to identify metabolites in different sample types (biological fluids and tissues). Since OSCC promotes metabolic reprogramming influenced by a combination of genetic predisposition and environmental factors, including tobacco and alcohol consumption, and viral infections, the identification of distinct metabolites through screening may aid in the diagnosis of this condition. Moreover, studies have shown the use of metabolites during the catalysis of epigenetic modification, indicating a link between epigenetics and metabolism. In this review, we will focus on the link between environmental, genetic, and epigenetic influences in metabolomic alterations in OSCC. In addition, we will discuss therapeutic targets of tumor metabolism, which may prevent oral tumor growth, metastasis, and drug resistance. [ABSTRACT FROM AUTHOR]

Numerous risk factors play a role in the causation of stroke, and the cardiometabolic condition is a one of the most important. In Korea, various treatment methods are employed based on the constitutional type, which is known to differ significantly in cardiometabolic disease. In this study, we compared the estimates obtained for different groups by applying the Mendelian randomization method to investigate the causal effects of genetic characteristics on stroke, according to constitutional type. In clinical analysis, the subtypes differ significantly in diabetes or dyslipidemia. The genetic association estimates for the stroke subtype risk were obtained from MEGASTROKE, the International Stroke Genetics Consortium (ISGC), UKbiobank, and BioBank Japan (BBJ), using group-related SNPs as instrumental variables. The TE subtypes with higher risk of metabolic disease were associated with increased risk (beta = 4.190; s.e. = 1.807; p = 0.035) of cardioembolic stroke (CES), and the SE subtypes were associated with decreased risk (beta = −9.336, s.e. = 1.753; p = 3.87 × 10−5) of CES. The findings highlight the importance of personalized medicine in assessing disease risk based on an individual's constitutional type. [ABSTRACT FROM AUTHOR]

Metabolic-associated fatty liver disease (MAFLD) is related to metabolic dysfunction and is characterized by excess fat storage in the liver. Several studies have indicated that glutamine could be closely associated with lipid metabolism disturbances because of its important role in intermediary metabolism. However, the effect of glutamine supplementation on MAFLD progression remains unclear. Here, we used a high-fat diet (HFD)-induced MAFLD C57BL/6 mouse model, and glutamine was supplied in the drinking water at different time points for MAFLD prevention and reversal studies. A MAFLD prevention study was performed by feeding mice an HFD concomitant with 4% glutamine treatment for 24 weeks, whereas the MAFLD reversal study was performed based on 4% glutamine treatment for 13 weeks after feeding mice an HFD for 10 weeks. In the prevention study, glutamine treatment ameliorated serum lipid storage, hepatic lipid injury, and oxidative stress in HFD-induced obese mice, although glutamine supplementation did not affect body weight, glucose homeostasis, energy expenditure, and mitochondrial function. In the MAFLD reversal study, there were no noticeable changes in the basic physiological phenotype and hepatic lipid metabolism. In summary, glutamine might prevent, but not reverse, HFD-induced MAFLD in mice, suggesting that a cautious attitude is required regarding its use for MAFLD treatment. [ABSTRACT FROM AUTHOR]

Though binding sites for the complement factor C1q and the canonical fragment crystallizable (Fc) gamma receptors (Fc γ Rs) on immunoglobulin G (IgG) molecules overlap, how C1q decoration of immune complexes (ICs) influences their ability to engage Fc γ Rs remains unknown. In this report, we use recombinant human Fc multimers as stable IC mimics to show that C1q engagement of ICs directly and transiently inhibits their interactions with Fc γ RIII (CD16) on human natural killer (NK) cells. This inhibition occurs by C1q engagement alone as well as in concert with other serum factors. Furthermore, the inhibition of Fc γ RIII engagement mediated by avid binding of C1q to ICs is directly associated with IC size and dependent on the concentrations of both C1q and Fc multimers present. Functionally, C1q-mediated Fc blockade limits the ability of NK cells to induce the upregulation of the cosignaling molecule, 4-1BB (CD137), and to mediate antibody-dependent cell-mediated cytotoxicity (ADCC). Although C1q is traditionally viewed as a soluble effector molecule, we demonstrate that C1q may also take on the role of an "immunologic rheostat," buffering Fc γ R-mediated activation of immune cells by circulating ICs. These data define a novel role for C1q as a regulator of immune homeostasis and add to our growing understanding that complement factors mediate pleiotropic effects. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study?Whole‐body substrate utilisation is altered during exercise in hot environments, characterised by increased glycolytic metabolism: does heat stress alter the serum metabolome in response to high intensity exercise?What are the main finding and its importance?Alongside increases in glycolytic metabolite abundance, circulating amino acid concentrations are reduced following exercise under heat stress. Prior research has overlooked the impact of heat stress on protein metabolism during exercise, raising important practical implications for protein intake recommendations in the heat. Using untargeted metabolomics, we aimed to characterise the systemic impact of environmental heat stress during exercise. Twenty‐three trained male triathletes (V̇O2peak${\dot V_{{{\rm{O}}_2}{\rm{peak}}}}$ = 64.8 ± 9.2 ml kg min−1) completed a 30‐min exercise test in hot (35°C) and temperate (21°C) conditions. Venous blood samples were collected immediately pre‐ and post‐exercise, and the serum fraction was assessed via untargeted 1H‐NMR metabolomics. Data were analysed via uni‐ and multivariate analyses to identify differences between conditions. Mean power output was higher in temperate (231 ± 36 W) versus hot (223 ± 31 W) conditions (P < 0.001). Mean heart rate (temperate, 162 ± 10 beats min−1, hot, 167 ± 9 beats min−1, P < 0.001), peak core temperature (Trec), core temperature change (ΔTrec) (P < 0.001) and peak rating of perceived exertion (P = 0.005) were higher in hot versus temperate conditions. Change in metabolite abundance following exercise revealed distinct clustering following multivariate analysis. Six metabolites increased (2‐hydroxyvaleric acid, acetate, alanine, glucarate, glucose, lactate) in hot relative to temperate (P < 0.05) conditions. Leucine and lysine decreased in both conditions but to a greater extent in temperate conditions (P < 0.05). Citrate (P = 0.04) was greater in temperate conditions whilst creatinine decreased in hot conditions only (P > 0.05). Environmental heat stress increased glycolytic metabolite abundance and led to distinct alterations in the circulating amino acid availability, including increased alanine, glutamine, leucine and isoleucine. The data highlight the need for additional exercise nutrition and metabolism research, specifically focusing on protein requirements for exercise under heat stress. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the response of a targeted fraction of (168 metabolites) of the resting serum metabolome to 9 sessions of sprint interval training (SIT). Methods: Thirty-four recreationally active males provided resting blood samples before (baseline) and 48–72 h after (post) a short-term (9 sessions) cycle ergometer-based SIT intervention. A targeted analysis of 168 metabolites was performed on serum using liquid chromatography mass spectrometry (LC–MS). 160 distinct metabolites were identified and combined with 4 calculated metabolite sums and 3 calculated metabolite ratios creating a panel of 167 individual factors. Data were analysed using principal component analysis and univariate testing of all factors classified into 5 metabolite subgroups. Results: SIT improved anaerobic capacity measured by average power output during a Wingate test (p < 0.01; mean difference = 38 W, 95% confidence interval [26, 51]) and aerobic capacity measured by average power output in a 20 min cycling test (p < 0.01; 17 W [12, 23]). Limited separation was discernible in the targeted serum metabolome between baseline and post-intervention when projected on the first and second principal component(s). However, univariate testing identified 11 fatty acids that had lower concentrations (false discovery rate < 0.05) in post-intervention samples. Conclusions: These findings demonstrate that this short-term SIT intervention had limited effect on the serum metabolome at rest, but a subfraction of fatty acids are potentially sensitive to short-term exercise training. [ABSTRACT FROM AUTHOR]

Spaceflight entails a variety of environmental and psychological stressors that may have long-term physiological and genomic consequences. Metabolomics, an approach that investigates the terminal metabolic outputs of complex physiological alterations, considers the dynamic state of the human body and allows the identification and quantification of down-stream metabolites linked to up-stream physiological and genomic regulation by stress. Employing a metabolomics-based approach, this study investigated longitudinal metabolic perturbations of male (n = 40) and female (n = 11) astronauts on 4–6-month missions to the International Space Station (ISS). Proton nuclear magnetic resonance (1H-NMR) spectroscopy followed by univariate, multivariate and machine learning analyses were used on blood serum to examine sex-specific metabolic changes at various time points throughout the astronauts’ missions, and the metabolic effects of long-duration space travel. Space travel resulted in sex-specific changes in energy metabolism, bone mineral and muscle regulation, immunity, as well as macromolecule maintenance and synthesis. Additionally, metabolic signatures suggest differential metabolic responses—especially during the recovery period—with females requiring more time to adjust to return to Earth. These findings provide insight into the perturbations in glucose and amino acid metabolism and macromolecule biosynthesis that result from the stressors of long-duration spaceflight. Metabolomic biomarkers may provide a viable approach to predicting and diagnosing health risks associated with prolonged space travel and other physiological challenges on Earth. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) play a key role in cellular communication both in physiological conditions and in pathologies such as cancer. Emerging evidence has shown that EVs are active carriers of molecular cargo (e.g. protein and nucleic acids) and a powerful source of biomarkers and targets. While recent studies on EV‐associated DNA (EV‐DNA) in human biofluids have generated a large amount of data, there is currently no database that catalogues information on EV‐DNA. To fill this gap, we have manually curated a database of EV‐DNA data derived from human biofluids (liquid biopsy) and in‐vitro studies, called the Extracellular Vesicle‐Associated DNA Database (EV‐ADD). This database contains validated experimental details and data extracted from peer‐reviewed published literature. It can be easily queried to search for EV isolation methods and characterization, EV‐DNA isolation techniques, quality validation, DNA fragment size, volume of starting material, gene names and disease context. Currently, our database contains samples representing 23 diseases, with 13 different types of EV isolation techniques applied on eight different human biofluids (e.g. blood, saliva). In addition, EV‐ADD encompasses EV‐DNA data both representing the whole genome and specifically including oncogenes, such as KRAS, EGFR, BRAF, MYC, and mitochondrial DNA (mtDNA). An EV‐ADD data metric system was also integrated to assign a compliancy score to the MISEV guidelines based on experimental parameters reported in each study. While currently available databases document the presence of proteins, lipids, RNA and metabolites in EVs (e.g. Vesiclepedia, ExoCarta, ExoBCD, EVpedia, and EV‐TRACK), to the best of our knowledge, EV‐ADD is the first of its kind to compile all available EV‐DNA datasets derived from human biofluid samples. We believe that this database provides an important reference resource on EV‐DNA‐based liquid biopsy research, serving as a learning tool and to showcase the latest developments in the EV‐DNA field. EV‐ADD will be updated yearly as newly published EV‐DNA data becomes available and it is freely available at www.evdnadatabase.com. [ABSTRACT FROM AUTHOR]

The last two decades witnessed a significant advancement in the field of diluted and whole blood plasma separation. This is one of the common procedures used to diagnose, cure and treat numerous acute and chronic diseases. For this separation purpose, various types of geometries of microfluidic devices, such as T-channel, Y-channel, trifurcation, constriction–expansion, curved/bend/spiral channels, a combination of any of the two geometries, etc., are being exploited, and this is detailed in this review article. The evaluation of the performance of such devices is based on the several parameters such as separation efficiency, flow rate, hematocrits, channel dimensions, etc. Thus, the current extensive review article endeavours to understand how particular geometry influences the separation efficiency for a given hematocrit. Additionally, a comparative analysis of various geometries is presented to demonstrate the less explored geometric configuration for the diluted and whole blood plasma separation. Also, a meta-analysis has been performed to highlight which geometry serves best to give a consistent separation efficiency. This article also presents tabulated data for various geometries with necessary details required from a designer's perspective such as channel dimensions, targeted component, studied range of hematocrit and flow rate, separation efficiency, etc. The maximum separation efficiency that can be achieved for a given hematocrits and geometry has also been plotted. The current review highlights the critical findings relevant to this field, state of the art understanding and the future challenges. [ABSTRACT FROM AUTHOR]

Mammalian cell culture is a fundamental tool used to study living cells. Presently, the standard protocol for performing cell culture involves the use of commercial media that contain an excess of nutrients. Although this reduces the likelihood of cell starvation, it creates nonphysiologic culture conditions that have been shown to "re-wire" cellular metabolism. Recently, researchers have developed new media like Plasmax, formulated to approximate the nutrient composition of human blood plasma. Although this represents an improvement in cell culture practice, physiologic media may be vulnerable to nutrient depletion. In this study, we directly addressed this concern by measuring the rates of glucose and amino acid depletion from Plasmax in several cancer cell lines (PC-3, LNCaP, MCF-7, and SH-SY5Y) over 48 h. In all cell lines, depletion of glucose from Plasmax was rapid such that, by 48 h, cells were hypoglycemic (<2 mM glucose). Most amino acids were similarly rapidly depleted to subphysiological levels by 48 h. In contrast, glucose and most amino acids remained within the physiological range at 24 h. When the experiment was done at physiological oxygen (5%) versus standard (18%) with LNCaP cells, no effect on glucose or amino acid consumption was observed. Using RNA sequencing, we show that this nutrient depletion is associated with enrichment of starvation responses, apoptotic signaling, and endoplasmic reticulum stress. A shift from glycolytic metabolism to mitochondrial respiration at 5% O2 was also measured using Seahorse analysis. Taken together, these results exemplify the metabolic considerations for Plasmax, highlighting that cell culture in Plasmax requires daily media exchange. [ABSTRACT FROM AUTHOR]

Acylcarnitines (ACs) are metabolites involved in fatty acid β-oxidation and organic acid metabolism. Metabolic disorders associated to these two processes can be evaluated by determining the complete profile of ACs. In this research, we present an overall strategy for identification, confirmation, and quantitative determination of acylcarnitines in human serum. By this strategy we identified the presence of 47 ACs from C2 to C24 with detection of the unsaturation degree by application of a data-independent acquisition (DIA) liquid chromatography–tandem mass spectrometry (LC–MS/MS) method. Complementary, quantitative determination of ACs is based on a high-throughput and fully automated method consisting of solid-phase extraction on-line coupled to LC–MS/MS in data-dependent acquisition (DDA) to improve analytical features avoiding the errors associated to sample processing. Quantitation limits were at pg mL–1 level, the intra-day and between-day variability were below 15–20%, respectively; and the accuracy, expressed as bias, was always within ± 25%. The proposed method was tested with 40 human volunteers to determine the relative concentration of ACs in serum and identify predominant forms. Significant differences were detected by comparing the ACs profile of obese versus non-obese individuals. [ABSTRACT FROM AUTHOR]

Rationale: Matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOF MS) has exhibited great advantages in rapid analysis of metabolites. However, the influence of lipid fragments generated by in‐source fragmentation (ISD) and/or post‐source fragmentation (PSD) on the accurate qualification and quantification of metabolites has not been fully demonstrated. Methods: Phospholipid standards and serum extract were analyzed by MALDI MS with both TiO2 nanoparticle (TiO2NP) and 2,5‐DHB matrices to illustrate the structures of lipid fragments and their influence on the qualitative and quantitative analysis of metabolites in biological samples. Monophasic and biphasic extraction methods were also compared for their efficiency in removing potential interferents. Results: The fragment ions derived from the phosphocholine head group of phosphatidylcholines (PC) interfere with peaks of low molecular weight (LMW) metabolites at both the MS and MS2 levels. The biphasic extraction system with methanol/chloroform very efficiently removed the interference from PC fragments, and the metabolites choline and carnitine in serum were directly and accurately quantified by MALDI MS by using this biphasic extraction. Conclusions: The phospholipids could produce fragment ions through ISD and PSD in MALDI MS with both nanoparticle and organic matrices. The fragments exerted influence on the qualification and qualification of metabolites in serum. By choosing the proper extraction method, the interference from lipid fragments could be efficiently alleviated. [ABSTRACT FROM AUTHOR]

Metabolomics refers to the large-scale detection, quantification, and analysis of small molecules (metabolites) in biological media. Although metabolomics, alone or combined with other omics data, has already demonstrated its relevance for patient stratification in the frame of research projects and clinical studies, much remains to be done to move this approach to the clinical practice. This is especially true in the perspective of being applied to personalized/precision medicine, which aims at stratifying patients according to their risk of developing diseases, and tailoring medical treatments of patients according to individual characteristics in order to improve their efficacy and limit their toxicity. In this review article, we discuss the main challenges linked to analytical chemistry that need to be addressed to foster the implementation of metabolomics in the clinics and the use of the data produced by this approach in personalized medicine. First of all, there are already well-known issues related to untargeted metabolomics workflows at the levels of data production (lack of standardization), metabolite identification (small proportion of annotated features and identified metabolites), and data processing (from automatic detection of features to multi-omic data integration) that hamper the inter-operability and reusability of metabolomics data. Furthermore, the outputs of metabolomics workflows are complex molecular signatures of few tens of metabolites, often with small abundance variations, and obtained with expensive laboratory equipment. It is thus necessary to simplify these molecular signatures so that they can be produced and used in the field. This last point, which is still poorly addressed by the metabolomics community, may be crucial in a near future with the increased availability of molecular signatures of medical relevance and the increased societal demand for participatory medicine. [ABSTRACT FROM AUTHOR]

Background: Bipolar disorder (BD) is a chronic, debilitating illness with significant medical morbidity, often secondary to current treatments, and a high recurrence rate. This burden of disease reflects limitations in the tolerability and efficacy of current treatments. There is a compelling body of evidence linking the gut microbiota to mental illness, and while microbial manipulation via probiotic use has been studied as a therapeutic in BD, targeted trials of fecal microbiota transplantation (FMT) have not been conducted in this population. Methods and design: We describe a pilot randomized controlled trial of FMT in participants with BD depression to assess the feasibility, efficacy, safety, and tolerability of this intervention. Individuals between 18 and 65 years of age will be enrolled in the study if they meet diagnostic criteria for a major depressive episode of at least moderate severity in the context of a BD diagnosis and have not responded to treatment for BD. Participants will be randomized 1:1 to receive either screened and processed donor stool (allogenic FMT) or their own stool (autologous FMT) via colonoscopy and monitored for 24 weeks post intervention. Depressive and manic symptoms, treatment acceptability, and gastrointestinal and other side effects are assessed at baseline (prior to randomization) and weekly. Stool samples to assess microbiome composition are obtained at baseline and 3 and 6 months. Discussion: Currently, FMT represents a novel therapeutic option for treating BD depression. This protocol allows for the assessment of the feasibility, efficacy, acceptability, and safety of an intervention aimed at changing the microbiome in those with BD. Results from this pilot study will guide the development of larger trials of FMT for BD depression and may give more insight into how the gut microbiome are altered in those with BD depression. Trial registration: Clinical Trials Gov NCT03279224 [ABSTRACT FROM AUTHOR]

Metabolomics is one of the omics sciences, its technologies are widely used in many life sciences. Application of metabolomics had a significant impact on the discovery of new biomarkers of diseases, the description of biochemical processes occurring in many organisms; it created a basis for a new generation of clinical laboratory diagnostics. The purpose of this review is to demonstrate how metabolomics is represented in the studies of Russian scientists, to demonstrate the main directions and achievements of the Russian science in this field. The review also highlights the history of metabolomics, existing problems and the place of Russian metabolomics in their solution. [ABSTRACT FROM AUTHOR]

Unexpected viral infections outbreaks, significantly affect human health, leading to increased mortality and life disruption. Among them is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which emerged as a deadly pandemic, calling for intense research efforts on its pathogenicity mechanism and development of therapeutic strategies. In the SARS-CoV-2 cytokine storm, systemic inflammation has been associated with severe illness and mortality. Recent studies have demonstrated special pro-resolving lipids mediators (SPMs) lipoxins, resolvins, maresins, and protectins as potential therapeutic options for abnormal viral-triggered inflammation. Pro-resolving lipids mediators have shown great promise for the treatment of Herpes simplex virus, respiratory syncytial virus, human immunodeficiency virus, and hepatitis C virus. Based on this, studies are being conducted on their therapeutic effects in SARS-CoV-2 infection. In this review, we discussed SPMs and reviewed evidence from recent studies on SPMs as therapeutic options for viral infections, including SARS-CoV2. Based on our analysis of the previous study, we argue that SPMs are a potential treatment for SARS-CoV-2 infection and other viral infections. We expect further research on how SPMs modulate viral-triggered inflammation through G-protein-coupled receptors (GPCRs), and chemical stability and druggability of SPMs. [ABSTRACT FROM AUTHOR]

Background: Currently, there is no objective, clinically available tool for the accurate diagnosis of Alzheimer's disease (AD). There is a pressing need for a novel, minimally invasive, cost friendly, and easily accessible tool to diagnose AD, assess disease severity, and prognosticate course. Metabolomics is a promising tool for discovery of new, biologically, and clinically relevant biomarkers for AD detection and classification.Objective: Utilizing artificial intelligence and machine learning, we aim to assess whether a panel of metabolites as detected in plasma can be used as an objective and clinically feasible tool for the diagnosis of mild cognitive impairment (MCI) and AD.Methods: Using a community-based sample cohort acquired from different sites across the US, we adopted an approach combining Proton Nuclear Magnetic Resonance Spectroscopy (1H NMR), Liquid Chromatography coupled with Mass Spectrometry (LC-MS) and various machine learning statistical approaches to identify a biomarker panel capable of identifying those patients with AD and MCI from healthy controls.Results: Of the 212 measured metabolites, 5 were identified as optimal to discriminate between controls, and individuals with MCI or AD. Our models performed with AUC values in the range of 0.72-0.76, with the sensitivity and specificity values ranging from 0.75-0.85 and 0.69-0.81, respectively. Univariate and pathway analysis identified lipid metabolism as the most perturbed biochemical pathway in MCI and AD.Conclusion: A comprehensive method of acquiring metabolomics data, coupled with machine learning techniques, has identified a strong panel of diagnostic biomarkers capable of identifying individuals with MCI and AD. Further, our data confirm what other groups have reported, that lipid metabolism is significantly perturbed in those individuals suffering with dementia. This work may provide additional insight into AD pathogenesis and encourage more in-depth analysis of the AD lipidome. [ABSTRACT FROM AUTHOR]

The fabrication of a nanointerfaced electrochemical immunosensor is described for the rapid determination of cystatin C, a biomarker that is elevated in diabetic retinopathy. A dispersion of graphene oxide-chitosan (GO-Chit) nanocomposite was used to modify the carbon working electrode, allowing for a high conjugation of anti–cystatin C antibody. This modified sensor was characterized both morphologically and electrochemically, and the sensor performance was evaluated towards selective quantification of cystatin C in simulated as well as serum samples using cyclic voltammetry and differential pulse voltammetry. The sensor was able to detect cystatin C in the concentration range1 - 10 mg/L with a detection limit of 0.0078 mg/L. The preparation time of the sensor was 420 s, which was faster than that of conventional ELISA and other electrochemical sensors reported in literature. The clinical applicability of the proposed electrochemical biosensor was demonstrated through quantification of cystatin C in human serum samples and identification of diabetic retinopathy. A cutoff value of 1.2 mg/L of cystatin C was used beyond which the samples were classified as positive for diabetic retinopathy. Two different working electrodes, namely a glassy carbon electrode (GCE) and paper electrodes, were used in the study. The working potential was set to 0.25 V vs. Ag/AgCl for experiments with the GCE and 0.15 V for the paper electrodes. The prediction was validated by clinical diagnosis wherein the prediction accuracy of the sensor exceeded 85%. The sensor platform was translated onto a paper substrate and characterized for achieving an optimum sensing performance. This work is the first attempt to employ an electrochemical cystatin C sensor for the diagnosis of diabetic retinopathy from serum samples. [ABSTRACT FROM AUTHOR]

Feeding ruminants a high-grain (HG) diet is a widely used strategy to improve milk yield and cost efficiency. However, it may cause certain metabolic disorders. At present, information about the effects of HG diets on the systemic metabolic profile of goats and the correlation of such diets with rumen bacteria is limited. In the present study, goats were randomly divided into two groups: one was fed the hay diet (hay; n = 5), while the other was fed HG diets (HG; n = 5). On day 50, samples of rumen contents, peripheral blood serum and liver tissues were collected to determine the metabolic profiles in the rumen fluid, liver and serum and the microbial composition in rumen. The results revealed that HG diets reduced (P < 0.05) the community richness and diversity of rumen microbiota, with an increase in the Chao 1 and Shannon index and a decrease in the Simpson index. HG diets also altered the composition of rumen microbiota, with 30 genera affected (P < 0.05). Data on the metabolome showed that the metabolites in the rumen fluid, liver and serum were affected (variable importance projection > 1, P <0.05) by dietary treatment, with 47, 10 and 27 metabolites identified as differentially metabolites. Pathway analysis showed that the common metabolites in the shared key pathway (aminoacyl-transfer RNA biosynthesis) in the rumen fluid, liver and serum were glycine, lysine and valine. These findings suggested that HG diets changed the composition of the rumen microbiota and metabolites in the rumen fluid, liver and serum, mainly involved in amino acid metabolism. Our findings provide new insights into the understanding of diet-related systemic metabolism and the effects of HG diets on the overall health of goats. [ABSTRACT FROM AUTHOR]

Metabolomics uses advanced analytical chemistry techniques to enable the high-throughput characterization of metabolites from cells, organs, tissues, or biofluids. The rapid growth in metabolomics is leading to a renewed interest in metabolism and the role that small molecule metabolites play in many biological processes. As a result, traditional views of metabolites as being simply the “bricks and mortar” of cells or just the fuel for cellular energetics are being upended. Indeed, metabolites appear to have much more varied and far more important roles as signaling molecules, immune modulators, endogenous toxins, and environmental sensors. This review explores how metabolomics is yielding important new insights into a number of important biological and physiological processes. In particular, a major focus is on illustrating how metabolomics and discoveries made through metabolomics are improving our understanding of both normal physiology and the pathophysiology of many diseases. These discoveries are yielding new insights into how metabolites influence organ function, immune function, nutrient sensing, and gut physiology. Collectively, this work is leading to a much more unified and system-wide perspective of biology wherein metabolites, proteins, and genes are understood to interact synergistically to modify the actions and functions of organelles, organs, and organisms. [ABSTRACT FROM AUTHOR]

Objective: Osteoarthritis (OA), the most encountered arthritis form, result from degeneration of articular cartilage. Obesity is accepted as a significant risk factor for knee OA (KOA). In this study, it is aimed to determine the variation of metabolites between control and patients with KOA and observe the effect of obesity on KOA via untargeted metabolomics method. Methods: Serum samples of following groups were collected: patient group including 14 obesity (OKOA) and 14 non-obesity (NOKOA) (n = 28) and control group (n = 15) from orthopedics and traumatology policlinic. Serum proteins were denatured by acetonitrile and chromatographic separation of metabolites was achieved by LC/Q-TOF/MS/MS method. Data acquisition, classification, and identification were achieved by METLIN database. Cluster analysis was performed with MATLAB2017a-PLS Toolbox 7.2. Results: Obtained results showed that 244 (patient vs control) and 274 (OKOA vs NOKOA) m/z ratios were determined in accordance with LC/Q-TOF/MS/MS analysis. Multivariate data analysis was applied 41 and 36 m/z signal (p ≤ 0.01; fold analysis > 1.5) were filtered for patient vs control group and OKOA vs NOKOA, respectively. Twenty-one different metabolites were identified for patient vs control group and 15 metabolites were determined for OKOA vs NOKOA group. Conclusion: Acid concentration and oxidative stress agents were high in inflammation group and their levels were much higher in obesity. It is claimed that obesity cause oxidative stress and acidosis in arthritis patients. Valine was found to be the only BCAA molecule whose concentration has significantly different in KOA patients. The relation between KOA and obesity was firstly investigated with metabolomics method. [ABSTRACT FROM AUTHOR]

Ischemic heart disease (IHD) is the most common cause of death in the world. Metabolic profiling is an innovative and reliable new method to detect more sensitive biomarkers identifying altered health conditions specifically among the variety of patients with different risk factors. We evaluated the metabolic profile of filtered serum of stable IHD patients (ICD10 codes I20 and I25.2, ischemic heart disease without or with previous myocardial infarction respectively) using proton nuclear magnetic resonance spectroscopy (NMR). The filtered venous serum from age- and gender-matched stable IHD patients ICD10 coded I20 (n = 13), I25.2 (n = 6) and control individuals (n = 19) were analyzed using one-dimensional proton nuclear magnetic resonance (1H NMR) spectroscopy. These spectra were used for metabolic profiling and concentration calibration (Chenomx Inc.) followed by statistical analysis using one-way ANOVA and principal component analysis (PCA). Chemometrics analysis showed a significant distinction between the patients and control individuals. The stable IHD patients were exemplified by the increased concentration of acetylacetate, choline, betaine, formate, pyruvate and by the decreased concentration of alanine, creatine, glycine, histidine, lactate, proline, urea and other biomolecules. The major implications found in the serum of IHD patients are related to energy metabolism and potentially altered microbiome. PCA of 1H NMR detected serum metabolites exhibit a significant difference of stable IHD patients and control individuals. These data demonstrate that metabolomics approach may be useful for the early detection of stable IHD, for detection of synergistic pathways involved in the development of altered health conditions, and molecular understanding of particular health condition. The differences of the detected metabolic profile of ischemic patients with or without previous myocardial infarction appear to be minor. This relatively inexpensive, non-invasive and reproducible approach may be useful for the molecular understanding and early prevention of IHD, improvement of surveillance and therapy. The study emerges the need for future investigations using larger cohort and possible longitudinal sight. [ABSTRACT FROM AUTHOR]

Proton nuclear magnetic resonance (NMR) is useful for the analysis of biological samples such as serum. Free induction decays (FIDs) are NMR signals that follow a radio-frequency pulse applied at the resonance frequency. Short-time Fourier transform (STFT) is a basic method for time-frequency analyses. The purpose of this study was to ascertain whether the STFT of FIDs enables the sensitive detection of changes and differences in serum properties. FIDs were obtained from serum collected from young, healthy, male volunteers ≤ 40 years of age and seniors ≥ 65 years of age. Temporal changes in the instantaneous amplitudes for the time-domain analysis, fast Fourier transform for frequency-domain analysis, and STFT were applied to the FIDs. The STFT-based spectrogram represented the complex frequency components that changed dynamically over time, indicating that the spectrogram enabled the visualization of the features of an FID. Furthermore, the results of a partial least-squares discriminant analysis demonstrated that the STFT was superior to the other two methods for discriminating between serum from younger and older subjects. In conclusion, the STFT of FIDs obtained from proton NMR measurements was useful for evaluating similarities and dissimilarities in the FIDs obtained from serum samples. [ABSTRACT FROM AUTHOR]

The ultrahigh-performance liquid chromatography-mass spectrometry (UHPLC/MS) method was optimized and validated for the determination of oxylipins in human plasma using the targeted approach with selected reaction monitoring (SRM) in the negative-ion electrospray ionization (ESI) mode. Reversed phase UHPLC separation on an octadecylsilica column enabled the analysis of 63 oxylipins including numerous isomeric species within 12-min run time. The method was validated (calibration curve, linearity, limit of detection, limit of quantification, carry-over, precision, accuracy, recovery rate, and matrix effect) and applied to 40 human female plasma samples from breast cancer patients and age-matched healthy volunteers (control). Thirty-six oxylipins were detected in human plasma with concentrations above the limit of detection, and 21 of them were quantified with concentrations above the limit of quantitation. The concentrations determined in healthy controls are in a good agreement with previously reported data on human plasma. Quantitative data were statistically evaluated by multivariate data analysis (MDA) methods including principal component analysis (PCA) and orthogonal partial least square discriminant analysis (OPLS-DA). S-plot and box plots showed that 13-HODE, 9-HODE, 13-HOTrE, 9-HOTrE, and 12-HHTrE were the most upregulated oxylipin species in plasma of breast cancer patients. [ABSTRACT FROM AUTHOR]

One of the most striking adaptations to exercise is the skeletal muscle hypertrophy that occurs in response to resistance exercise. A large body of work shows that a mammalian target of rapamycin complex 1 (mTORC1)- mediated increase of muscle protein synthesis is the key, but not sole, mechanism by which resistance exercise causes muscle hypertrophy. While much of the hypertrophy signaling cascade has been identified, the initiating, resistance exercise-induced and hypertrophy-stimulating stimuli have remained elusive. For the purpose of this review, we define an initiating, resistance exercise-induced and hypertrophy-stimulating signal as “hypertrophy stimulus,” and the sensor of such a signal as “hypertrophy sensor.” In this review we discuss our current knowledge of specific mechanical stimuli, damage/injury-associated and metabolic stress-associated triggers, as potential hypertrophy stimuli. Mechanical signals are the prime hypertrophy stimuli candidates, and a filamin-C-BAG3-dependent regulation of mTORC1, Hippo, and autophagy signaling is a plausible albeit still incompletely characterized hypertrophy sensor. Other candidate mechanosensing mechanisms are nuclear deformation-initiated signaling or several mechanisms related to costameres, which are the functional equivalents of focal adhesions in other cells. While exercise-induced muscle damage is probably not essential for hypertrophy, it is still unclear whether and how such muscle damage could augment a hypertrophic response. Interventions that combine blood flow restriction and especially low load resistance exercise suggest that resistance exercise-regulated metabolites could be hypertrophy stimuli, but this is based on indirect evidence and metabolite candidates are poorly characterized. [ABSTRACT FROM AUTHOR]

With the advent of antiretroviral therapy (ART), HIV-infected individuals are now living longer and healthier lives. However, ART does not completely restore health and treated individuals are experiencing increased rates of noncommunicable diseases such as dyslipidemia, insulin resistance, type 2 diabetes, cardiovascular disease, and nonalcoholic fatty liver disease. While it is well known that persistent immune activation and inflammation contribute to the development of these comorbid diseases, the mechanisms underlying this chronic activation remain incompletely understood. In this review, we will discuss emerging evidence that suggests that alterations in cellular metabolism may play a central role in driving this immune dysfunction in HIV patients on ART. [ABSTRACT FROM AUTHOR]

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Although it is common in untargeted metabolomics to apply reversed-phase liquid chromatography (RPLC) and hydrophilic interaction liquid chromatography (HILIC) methods that have been systematically optimized for lipids and central carbon metabolites, here we show that these established protocols provide poor coverage of semipolar metabolites because of inadequate retention. Our objective was to develop an RPLC approach that improved detection of these metabolites without sacrificing lipid coverage. We initially evaluated columns recently released by Waters under the CORTECS line by analyzing 47 small-molecule standards that evenly span the nonpolar and semipolar ranges. An RPLC method commonly used in untargeted metabolomics was considered a benchmarking reference. We found that highly nonpolar and semipolar metabolites cannot be reliably profiled with any single method because of retention and solubility limitations of the injection solvent. Instead, we optimized a multiplexed approach using the CORTECS T3 column to analyze semipolar compounds and the CORTECS C column to analyze lipids. Strikingly, we determined that combining these methods allowed detection of 41 of the total 47 standards, whereas our reference RPLC method detected only 10 of the 47 standards. We then applied credentialing to compare method performance at the comprehensive scale. The tandem method showed more than a fivefold increase in credentialing coverage relative to our RPLC benchmark. Our results demonstrate that comprehensive coverage of metabolites amenable to reversed-phase separation necessitates two reconstitution solvents and chromatographic methods. Thus, we suggest complementing HILIC methods with a dual T3 and C RPLC approach to increase coverage of semipolar metabolites and lipids for untargeted metabolomics. [ABSTRACT FROM AUTHOR]

The work describes the development of an enrichment method for the analysis of endogenous phosphopeptides in serum. Endogenous peptides can play significant biological roles, and some of them could be exploited as future biomarkers. In this context, blood is one of the most useful biofluids for screening, but a systematic investigation of the endogenous peptides, especially phosphorylated ones, is still lacking, mainly due to the lack of suitable analytical methods. Thus, in this paper, different phosphopeptide enrichment strategies were pursued, based either on metal oxide affinity chromatography (MOAC, in the form of commercial TiO spin columns or magnetic graphitized carbon black-TiO composite), or on immobilized metal ion affinity chromatography (IMAC, in the form of Ti-IMAC magnetic material or commercial Fe-IMAC spin columns). While MOAC strategies proved completely unsuccessful, probably due to interfering phospholipids displacing phosphopeptides, the IMAC materials performed very well. Different sample preparation strategies were tested, comprising direct dilution with the loading buffer, organic solvent precipitation, and lipid removal from the matrix, as well as the addition of phosphatase inhibitors during sample handling for maximized endogenous phosphopeptide enrichment. All data were acquired by a shotgun peptidomics approach, in which peptide samples were separated by reversed-phase nanoHPLC hyphenated with high-resolution tandem mass spectrometry. The devised method allowed the identification of 176 endogenous phosphopeptides in fresh serum added with inhibitors by the direct dilution protocol and the Ti-IMAC magnetic material enrichment, but good results could also be obtained from the commercial Fe-IMAC spin column adapted to the batch enrichment protocol. [ABSTRACT FROM AUTHOR]

Oxylipins are a group of fatty acid metabolites generated via oxygenation of polyunsaturated fatty acids and are involved in processes such as inflammation, immunity, pain, vascular tone, and coagulation. As a result, oxylipins have been implicated in many conditions characterized by these processes, including cardiovascular disease and aging. The best characterized oxylipins in relation to cardiovascular disease are derived from the ω-6 fatty acid arachidonic acid. These oxylipins generally increase inflammation, hypertension, and platelet aggregation, although not universally. Similarly, oxylipins derived from the ω-6 fatty acid linoleic acid generally have more adverse than beneficial cardiovascular effects. Alternatively, most oxylipins derived from 20- and 22-carbon ω-3 fatty acids have anti-inflammatory, antiaggregatory, and vasodilatory effects that help explain the cardioprotective effects of these fatty acids. Much less is known regarding the oxylipins derived from the 18-carbon ω-3 fatty acid α-linolenic acid, but clinical trials with flaxseed supplementation have indicated that these oxylipins can have positive effects on blood pressure. Normal aging also is associated with changes in oxylipin levels in the brain, vasculature, and other tissues, indicating that oxylipin changes with aging may be involved in age-related changes in these tissues. A small number of trials in humans and animals with interventions that contain either 18-carbon or 20- and 22-carbon ω-3 fatty acids have indicated that dietary-induced changes in oxylipins may be beneficial in slowing the changes associated with normal aging. In summary, oxylipins are an important group of molecules amenable to dietary manipulation to target cardiovascular disease and age-related degeneration. [ABSTRACT FROM AUTHOR]

Current studies related to lipid identification and determination, or lipidomics in biological samples, are one of the most important issues in modern bioanalytical chemistry. There are many articles dedicated to specific analytical strategies used in lipidomics in various kinds of biological samples. However, in such literature, there is a lack of articles dedicated to a comprehensive review of the actual analytical methodologies used in lipidomics. The aim of this article is to characterize the lipidomics methods used in modern bioanalysis according to the methodological point of view: (1)chromatography/separationmethods, (2)spectroscopicmethods and (3)mass spectrometryand alsohyphenatedmethods. In the first part, we discussed thin layer chromatography (TLC), high-pressure liquid chromatography (HPLC), gas chromatography (GC) and capillary electrophoresis (CE). The second part includes spectroscopic techniques such as Raman spectroscopy (RS), Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance (NMR). The third part is a synthetic review of mass spectrometry,matrix-assisted laser desorption/ionization(MALDI), hyphenated methods, which include liquid chromatography–mass spectrometry (LC-MS), gas chromatography–mass spectrometry (GC-MS) and also multidimensional techniques. Other aspects are the possibilities of the application of the described methods in lipidomics studies. Due to the fact that the exploration of new methods of lipidomics analysis and their applications in clinical and medical studies are still challenging for researchers working in life science, we hope that this review article will be very useful for readers. [ABSTRACT FROM PUBLISHER]

Raman spectroscopy has been employed in the quantitative analysis of biochemical components in human serum. This study aimed to develop a spectral model to estimate the concentration of glucose and lipid fractions in human serum, thus evaluating the feasibility of Raman spectroscopy technique for diagnostic purposes. A total of 44 samples of blood serum were collected from volunteers submitted to routine blood biochemical assay analysis. The biochemical concentrations of glucose, triglycerides, cholesterol, and high-density and low-density lipoproteins (HDL and LDL) were obtained by colorimetric method. Serum samples (200 μL) were submitted to Raman spectroscopy (830 nm, 250 mW, 50-s accumulation). The spectra of sera present peaks related to the main constituents, particularly proteins and lipids. A quantitative model based on partial least squares (PLS) regression has been developed to estimate the concentration of these compounds, taking the biochemical concentrations assayed by the colorimetric method as sample's actual concentrations. The PLS model based on leave-one-out cross-validation approach estimated the concentration of triglycerides and cholesterol with r = 0.98 and 0.96, and root mean square error of 35.4 and 15.9 mg/dL, respectively. For the other biochemicals, the r was ranging from 0.75 to 0.86. These results evidenced the possibility of performing biochemical assay in blood serum samples by Raman spectroscopy and PLS regression and may be employed as a means of diagnosis in routine clinical analysis. [ABSTRACT FROM AUTHOR]

Purpose: Substantial intrafraction organ motion during radiation therapy (RT) for pancreatic cancer is well recognized as a major limiting factor for accurate delivery of RT. The aim of this work is to determine the feasibility of monitoring the intrafractional motion of the pancreas or surrounding structures using ultrasound for RT delivery. Methods: Transabdominal ultrasound (TAUS) and 4DCT data were acquired on ten pancreatic cancer patients during radiation therapy process in a prospective study. In addition, TAUS and MRI were collected for five healthy volunteers. The portal vein (PV) and the head of the pancreas (HP) along with other structures were contoured on these images. Volume changes, distance between the HP and PV, and motion difference between the HP and PV were measured to examine whether PV can be used as a motion surrogate for HP. TAUS images were acquired and processed using a research version of the Clarity autoscan ultrasound system (CAUS). Motion monitoring was performed with the ultrasound probe mounted on an arm fixed to the couch. Video segments of the monitoring sessions were captured. Results: On TAUS, PV is better visualized than HP. The measured mean volume deviation for all patients for the HP and PV was 1.4 and 0.6 ml, respectively. The distance between the HP and PV was close to a constant with 0.22 mm mean deviation throughout the ten breathing phases. The mean of the absolute motion difference for all patients was 1.7±0.8 mm in LR, 1.5±0.5 mm in AP, and 2.3±0.7 mm in SI, suggesting that the PV is a good surrogate for HP motion estimation. By using this surrogate, the HP motion tracking using TAUS was demonstrated. Conclusions: Large intrafractional organ motion due to respiratory and/or bowel motion is a limiting factor in administering curative radiation doses to pancreatic tumors. The authors investigate the use of real-time ultrasound to track pancreas motion. Due to the poor visibility of the pancreas head on an ultrasound image, the portal vein is identified as a surrogate. The authors have demonstrated the feasibility of tracking HP motion through the localization of the PV using TAUS. This will potentially allow real-time tracking of intrafractional motion to justify small PTV-margins and to account for unusual motions, thus, improving normal tissue sparing. [ABSTRACT FROM AUTHOR]

Miniaturized on-chip blood separators have a great value for point-of-care diagnosis. In our work, a combined design strategy-microfiltration, sedimentation in a retarded flow, and wetting contrast-was taken to overcome the known limitations of on-chip blood separators. Our microfluidic chip consists of a polydimethylsiloxane micropillar array and an etched glass with microchannel branches. The red blood cells are significantly slowed and gradually settled down due to micropillars and enlarged dimension of a chamber. An etched glass microchannel allows the extraction of blood plasma exclusively due to the capillary effect. The fabricated microfluidic device can separate blood plasma from a whole blood sample without any external driving force or dilution. The measured plasma separation efficiency was close to 100 % from human whole blood. Autonomous on-chip separation and collection of blood plasma was demonstrated. [ABSTRACT FROM AUTHOR]

Breast cancer is the most commonly diagnosed cancer and one of the leading causes of cancer death among women worldwide. It is a biologically variable disease with different molecular subtypes, risk factors, clinical behaviors and responses to treatment. Better understanding of the molecular changes associated with each subtype is essential for identifying new therapeutic targets and markers for the monitoring of treatment responses. In this pilot study, mass spectrometry-based metabolic profiling was performed to characterize the changes in serum profiles of patients with invasive ductal carcinoma (IDC) - the most common type of breast cancer. Serum samples from 20 IDC patients and 20 age- and gender-matched healthy subjects were analyzed and 15 differentially expressed metabolites were identified. These metabolites are involved in several metabolic pathways such as sphingolipid metabolism, phospholipid metabolism and fatty acid β-oxidation. Among these, two classes of signaling lipids, lysophosphatidylethanolamine and ceramide, may play an important role in IDC development and progression. This study demonstrates metabolic profiling as a promising tool for finding disease biomarkers and our findings provide new directions for further mechanistic studies on the pathology of IDC. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

In clinical practice, one objective is to obtain diagnostic information while minimizing the invasiveness of the tests and the pain for the patients. To this end, tests based on the interaction of light with readily available biofluids including blood, urine, or saliva are highly desirable. In this review we examine the state of the art regarding the use of surface-enhanced Raman spectroscopy (SERS) to investigate biofluids, focusing on diagnostic applications. First, a critical evaluation of the experimental aspects involved in the collection of SERS spectra is presented; different substrate types are introduced, with a clear distinction between colloidal and non-colloidal metal nanostructures. Then the effect of the excitation wavelength is discussed, along with anomalous bands and artifacts which might affect SERS spectra of biofluids. The central part of the review examines the literature available on the SERS spectra of blood, plasma, serum, urine, saliva, tears, and semen. Finally, diagnostic applications are critically discussed in the context of the published evidence; this section clearly reveals that SERS of biofluids is most promising as a rapid, cheap, and non-invasive tool for mass screening for cancer. [ABSTRACT FROM AUTHOR]

A liquid chromatography-mass spectrometry (LC-MS) method coupled with specialized sample-preparation strategies was developed to investigate the hydrolysis of ginkgolide B (GB) in physiological environments in comparison with that of ginkgolide A (GA). The rapid hydrolysis processes were captured by the direct injection of samples prepared in the volatile buffers. The LC-MS behavior of the hydrolyzed products, including three monocarboxylates and three dicarboxylates, was acquired. The monocarboxylates were identified by fragmentation analysis, and the dicarboxylates were accordingly tentatively identified by reaction sequences. The base-catalyzed hydrolysis of GB and GA was characterized at 4 °C within pH 7.0-10.7. The regioselective reactions on the lactone-C and lactone-F were revealed by thermodynamic studies at pH 6.8 and 7.4. It was revealed that the 1-hydroxyl group on the skeleton of GB blocks the reactivity of the lactone-E. On the basis of these results, a distinctive hydrolysis phenomenon of GB was confirmed in plasma of humans, rats, and dogs as a rapid degradation of the trilactone along with the only production of the lactone-F-hydrolyzed product. This phenomenon is also closely associated with the 1-hydroxyl group, because it was not observed in GA. More interestingly, the underlying mechanism was revealed not to be associated with any typical enzyme-catalyzed process, but to be potentially involved with a selective reaction of the intact or broken lactone-C moiety with endogenous small-molecule reactants in plasma. This in-depth knowledge of the hydrolysis of GB versus GA not only facilitated understanding of their pharmacological mechanisms but also provided potential routes to study the structure-activity relationships of ginkgolides. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

In this contribution, we investigated whether surface-enhanced Raman scattering (SERS) of serum can be a candidate method for detecting 'luminal A' breast cancer (BC) at different stages. We selected three groups of participants aged over 50 years: 20 healthy women, 20 women with early localized small BC, and 20 women affected by BC with lymph node involvement. SERS revealed clear spectral differences between these three groups. A predictive model using principal component analysis (PCA) and linear discriminant analysis (LDA) was developed based on spectral data, and its performance was estimated with cross-validation. PCA-LDA of SERS spectra could distinguish healthy from BC subjects (sensitivity, 92 %; specificity, 85 %), as well as subjects with BC at different stages, with a promising diagnostic performance (sensitivity and specificity, ≥80 %; overall accuracy, 84 %). Our data suggest that SERS spectroscopy of serum, combined with multivariate data analysis, represents a minimally invasive, easy to use, and fast approach to discriminate healthy from BC subjects and even to distinguish BC at different clinical stages. [ABSTRACT FROM AUTHOR]