In-vitro metabolite and drug detection rely on designed materials-based analytical platforms, which are universally used in biomedical research and clinical practice. However, metabolic analysis in ...bio-samples needs tedious sample preparation, due to the sample complexity and low molecular abundance. A further challenge is to construct diagnostic tools. Herein, we developed a platform using silver nanoshells. We synthesized SiO
@Ag with tunable shell structures by multi-cycled silver mirror reactions. Optimized nanoshells achieved direct laser desorption/ionization mass spectrometry in 0.5 μL of bio-fluids. We applied these nanoshells for disease diagnosis and therapeutic evaluation. We identified patients with postoperative brain infection through daily monitoring and glucose quantitation in cerebrospinal fluid. We measured drug distribution in blood and cerebrospinal fluid systems and validated the function of blood-brain/cerebrospinal fluid-barriers for pharmacokinetics. Our work sheds light on the design of materials for advanced metabolic analysis and precision diagnostics.Preparation of samples for diagnosis can affect the detection of biomarkers and metabolites. Here, the authors use a silver nanoparticle plasmonics approach for the detection of biomarkers in patients as well as investigate the distribution of drugs in serum and cerebral spinal fluid.
Intracranial bacterial infection remains a major cause of morbidity and mortality in neurosurgical cases. Metabolomic profiling of cerebrospinal fluid (CSF) holds great promise to gain insights into ...the pathogenesis of central neural system (CNS) bacterial infections. In this pilot study, we analyzed the metabolites in CSF of CNS infection patients and controls in a pseudo-targeted manner, aiming at elucidating the metabolic dysregulation in response to postoperative intracranial bacterial infection of pediatric cases. Untargeted analysis uncovered 597 metabolites, and screened out 206 differential metabolites in case of infection. Targeted verification and pathway analysis filtered out the glycolysis, amino acids metabolism and purine metabolism pathways as potential pathological pathways. These perturbed pathways are involved in the infection-induced oxidative stress and immune response. Characterization of the infection-induced metabolic changes can provide robust biomarkers of CNS bacterial infection for clinical diagnosis, novel pathways for pathological investigation, and new targets for treatment.
Monitoring of cerebrospinal fluid (CSF) microRNAs (miRs) offers a promising option for the diagnosis and management of patients with central nervous system tumors. However, the sensitive detection of ...miRs in clinical CSF samples has been hindered by the ultra-low abundance of target miRs. Here, we report an electrochemical biosensor for the highly sensitive label-free detection of CSF miR-21 relying on target-induced redox signal amplification (eTIRSA). The biosensor was developed by covalently assembling the capture stands partially complementary to miR-21 on the gold nanoparticle-coated glassy carbon electrode. In the presence of miR-21, the short capture stand hybridized with the partial bases of miR-21, allowing the rest sequence of the target molecule to further bind with a long guanine-rich sequence which could specifically adsorb a number of methylene blue indicators, thus generating an amplified electrochemical redox signal, typically at a working potential of − 0.19 V (vs. SCE). The response of the surface-bound methylene blue indicators was positively correlated to the concentration of miR-21, providing a dynamic range of 0.5–80 pM and a limit of detection down to 56 fM. Moreover, the eTIRSA biosensor had high specificity with single-base resolution and exhibited good performance for label-free quantification of miR-21 in medulloblastoma cell extracts and clinical CSF samples and for accurate discrimination of medulloblastoma against non-cancer controls, indicating its potential application in CSF miR-based liquid biopsy of brain cancers.
Graphical abstract
We recently showed that activation of G protein-coupled receptor 119 (GPR119) (also termed glucose dependent insulinotropic receptor) improves glucose homeostasis via direct cAMP-mediated enhancement ...of glucose-dependent insulin release in pancreatic β-cells. Here we show that GPR119 also stimulates incretin hormone release and thus may regulate glucose homeostasis by this additional mechanism. GPR119 mRNA was found to be expressed at significant levels in intestinal subregions that produce glucose-dependent insulinotropic peptide and glucagon-like peptide (GLP)-1. Furthermore, in situ hybridization studies indicated that most GLP-1-producing cells coexpress GPR119 mRNA. In GLUTag cells, a well-established model of intestinal L-cell function, the potent GPR119 agonist AR231453 stimulated cAMP accumulation and GLP-1 release. When administered in mice, AR231453 increased active GLP-1 levels within 2 min after oral glucose delivery and substantially enhanced total glucose-dependent insulinotropic peptide levels. Blockade of GLP-1 receptor signaling with exendin(9–39) reduced the ability of AR231453 to improve glucose tolerance in mice. Conversely, combined administration of AR231453 and the DPP-4 inhibitor sitagliptin to wild-type mice significantly amplified both plasma GLP-1 levels and oral glucose tolerance, relative to either agent alone. In mice lacking GPR119, no such enhancement was seen. Thus, GPR119 regulates glucose tolerance by acting on intestinal endocrine cells as well as pancreatic β-cells. These data also suggest that combined stimulation of incretin hormone release and protection against incretin hormone degradation may be an effective antidiabetic strategy.
The available data on the significance of circulating apelin, chemerin and omentin in women with gestational diabetes mellitus (GDM) are inconsistent. This analysis includes a systematic review of ...the evidence associating the serum concentrations of these adipokines with GDM.
Publications through December 2019 were retrieved from PubMed, Embase, the Cochrane Library, and Web of Science. Subgroup analysis and meta-regression were conducted to evaluate sources of heterogeneity.
Analysis of 20 studies, including 1493 GDM patients and 1488 normal pregnant women did not find significant differences in circulating apelin and chemerin levels (apelin standardized mean difference SMD = 0.43, 95% confidence interval (CI): - 0.40 to 1.26, P = 0.31; chemerin SMD = 0.77, 95% CI - 0.07 to 1.61, P = 0.07). Circulating omentin was significantly lower in women with GDM than in healthy controls (SMD = - 0.72, 95% CI - 1.26 to - 0.19, P = 0.007). Publication bias was not found; sensitivity analysis confirmed the robustness of the pooled results.
Circulating omentin was decreased in GDM patients, but apelin and chemerin levels were not changed. The results suggest that omentin has potential as a novel biomarker for the prediction and early diagnosis of GDM.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Current metabolic analysis is far from ideal to engage clinics and needs rationally designed materials and device. Here we developed a novel plasmonic chip for clinical metabolic fingerprinting. We ...first constructed a series of chips with gold nanoshells on the surface through controlled particle synthesis, dip-coating, and gold sputtering for mass production. We integrated the optimized chip with microarrays for laboratory automation and micro-/nanoscaled experiments, which afforded direct high-performance metabolic fingerprinting by laser desorption/ionization mass spectrometry using 500 nL of various biofluids and exosomes. Further we for the first time demonstrated on-chip in vitro metabolic diagnosis of early stage lung cancer patients using serum and exosomes. This work initiates a new bionanotechnology based platform for advanced metabolic analysis toward large-scale diagnostic use.
Heavy exercise or oxygen deficit often links with higher levels of arterial lactate and lower levels of plasma free fatty acids (FFA). Treatment with lactate reduces circulating levels of FFA
in vivo ...and lipolysis in adipose tissues
in vitro. However, the underlying mechanism has remained unclear. Here we employ pharmacological and genetic approaches to show that GPR81, an orphan G-protein-coupled receptor with relatively restricted expression in the adipose tissues, functions as a receptor for lactate and can mediate an anti-lipolytic effect of lactate. GPR81 may thus function as a sensor of lactate that can modulate the FFA pool under exercise or conditions of oxygen deficit.
Reliable monitoring of metabolites in biofluids is critical for diagnosis, treatment, and long‐term management of various diseases. Although widely used, existing enzymatic metabolite assays face ...challenges in clinical practice primarily due to the susceptibility of enzyme activity to external conditions and the low sensitivity of sensing strategies. Inspired by the micro/nanoscale confined catalytic environment in living cells, the coencapsulation of oxidoreductase and metal nanoparticles within the nanopores of macroporous silica foams to fabricate all‐in‐one bio‐nanoreactors is reported herein for use in surface‐enhanced Raman scattering (SERS)‐based metabolic assays. The enhancement of catalytical activity and stability of enzyme against high temperatures, long‐time storage or proteolytic agents are demonstrated. The nanoreactors recognize and catalyze oxidation of the metabolite, and provide ratiometric SERS response in the presence of the enzymatic by‐product H2O2, enabling sensitive metabolite quantification in a “sample in and answer out” manner. The nanoreactor makes any oxidoreductase‐responsible metabolite a candidate for quantitative SERS sensing, as shown for glucose and lactate. Glucose levels of patients with bacterial infection are accurately analyzed with only 20 µL of cerebrospinal fluids, indicating the potential application of the nanoreactor in vitro clinical testing.
Inspired by the spatially confined micro‐/nano‐environment in living cells, a plasmonic bio‐nanoreactor is developed by the coencapsulation of enzyme and surface‐enhanced Raman scattering tags within macroporous silica foams. The nanoreactor shows enhanced biocatalytic activity and stability, and thus the capability of molecular recognition and detection provides an all‐in‐one optical biosensor for reliable in vitro metabolic testing.
The aim of this study was to investigate the role of BTBD10 in glioma tumorigenesis. The mRNA and protein levels of BTBD10 in 52 glioma tissues and eight normal brain tissues were determined using ...reverse transcription polymerase chain reaction (RT-PCR) and western blot analysis, respectively. U251 human glioblastoma cells were infected with BTBD10-expressing or control lentiviruses. Cell growth was evaluated using the methyl thiazolyl tetrazolium (MTT) assay. Cell apoptosis and cell cycle distribution were analyzed using flow cytometry. Cyclin D1 and p-Akt levels were determined using western blot analysis. The results showed that BTBD10 mRNA and protein levels were significantly lower in glioma tissues than in normal brain tissues. Additionally, BTBD10 levels were significantly lower in high-grade gliomas than in low-grade tumors. Compared with control cells, U251 cells overexpressing BTBD10 exhibited decreased cell proliferation, increased cell accumulation at the G0/G1 phase, increased cell apoptosis, and decreased levels of cyclin D1 and p-Akt. These findings show that BTBD10 is downregulated in human glioma tissue and that BTBD10 expression negatively correlates with the pathological grade of the tumor. Furthermore, BTBD10 overexpression inhibits proliferation, induces G0/G1 arrest, and promotes apoptosis in human glioblastoma cells by downregulating cyclin D1- and Akt-dependent signaling pathways.
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