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Early prostatic cancer (PCa) diagnosis significantly improves the chances of successful treatment and enhances patient survival rates. Traditional enzyme cascade-based early cancer detection methods offer efficiency and signal amplification but are limited by cost, complexity, and enzyme dependency, affecting stability and practicality. Meanwhile, sarcosine (Sar) is commonly considered a biomarker for PCa development. It is essential to develop a Sar detection method based on cascade reactions, which should be efficient, low skill requirement, and suitable for on-site testing. To address this, our study introduces the synthesis of organic-inorganic self-assembled nanoflowers to optimize existing detection methods. The Sar oxidase (SOX)-inorganic hybrid nanoflowers (Cu 3 (PO 4) 2 :Ce@SOX) possess inherent fluorescent properties and excellent peroxidase activity, coupled with efficient enzyme loading. Based on this, we have developed a dual-mode multi-enzyme cascade nanoplatform combining fluorescence and colorimetric methods for the detection of Sar. The encapsulation yield of Cu 3 (PO 4) 2 :Ce@SOX reaches 84.5 %, exhibiting a remarkable enhancement in catalytic activity by 1.26–1.29 fold compared to free SOX. The present study employing a dual-signal mechanism encompasses 'turn-off' fluorescence signals ranging from 0.5 μM to 60 μM, with a detection limit of 0.226 μM, and 'turn-on' colorimetric signals ranging from 0.18 μM to 60 μM, with a detection limit of 0.120 μM. Furthermore, our study developed an intelligent smartphone sensor system utilizing cotton swabs for real-time analysis of Sar without additional instruments. The nano-platform exhibits exceptional repeatability and stability, rendering it well-suited for detecting Sar in authentic human urine samples. This innovation allows for immediate analysis, offering valuable insights for portable and efficient biosensors applicable to Sar and other analytes. A fluorescence and smartphone colorimetric sensing dual-mode multienzyme cascade based on oxidation-induced self-assembled nanoflowers for sarcosine's sensitive and selective detection. [Display omitted] • The simple synthesis method includes SOX as part of the enzyme-like catalyst. • The fluorescence was quenched by the SOX + Sar system, with activating nanozyme activity. • The generated H 2 O 2 has the effect of killing two birds with one stone for the cascade reaction system. • A chromogenic cotton swabs-based smartphone sensing system was developed for sarcosine analysis. [ABSTRACT FROM AUTHOR]

This article presents the development of a photothermal biosensing integrated with microfluidic paper-based analytical device (PT-μPAD) as a quantitative biosensor method for monitoring sarcosine in human control urine, plasma, and serum samples. The device utilizes gold nanoparticles (AuNPs) as both a peroxidase-like nanozyme and a photothermal substrate to enable sarcosine detection. In our PT-μPAD, hydrogen peroxide (H 2 O 2) is generated through the oxidation of sarcosine by a sarcosine oxidase (SOx) enzyme. Subsequently, the H 2 O 2 flows through the paper microchannels to the detection zone, where it etches the pre-deposited AuNPs, inducing a temperature change upon exposure by a 532 nm laser. The temperature variation is then measured using a portable and inexpensive infrared thermometer. Under optimized conditions, we obtained a linear range between 10.0 and 40.0 nmol L−1 (R2 = 0.9954) and a detection limit (LOD) of 32.0 pmol L−1. These values fall within the clinical range for sarcosine monitoring in prostate cancer diagnostics in humans. Moreover, our approach exhibits high selectivity without interfering effects. Recovery studies in various human control samples demonstrated a range of 99.05–102.11 % with the highest RSD of 2.25 %. The PT-μPAD was further validated for sarcosine determination in human control urine and compared with a commercial ELISA assay, revealing no significant difference between these two methods at a 95 % confidence level. Overall, our proposed sarcosine biosensor is well-suited for prostate cancer monitoring, given its affordability, sensitivity, and user-friendliness, even for unskilled individuals. Moreover, this strategy has promising prospects for broader applications, potentially detecting various biomarkers as a point-of-care (POC) diagnostic tool. [Display omitted] • We report the application of photothermal biosensing-based μPADs for sarcosine monitoring. • AuNPs application on μPADs is utilized as a peroxidase-like nanozyme and a photothermal substrate. • High sensitivity with a detection limit of 32.0 pg mL−1 is obtained. • The technique is faster than the same assay in the solution phase. • The analytical characteristic is well-suited for sarcosine detection in the clinical relevance. [ABSTRACT FROM AUTHOR]

Screen-printing technology is a game changer in many fields including electrochemical biosensing. Two-dimensional nanomaterial MXene Ti3C2Tx was integrated as a nanoplatform to immobilise enzyme sarcosine oxidase (SOx) onto the interface of screen-printed carbon electrodes (SPCEs). A miniaturised, portable, and cost-effective nanobiosensor was constructed using chitosan as a biocompatible glue for the ultrasensitive detection of prostate cancer biomarker sarcosine. The fabricated device was characterised with energy-dispersive X-ray spectroscopy (EDX), electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). Sarcosine was detected indirectly via the amperometric detection of H2O2 formed during enzymatic reaction. The nanobiosensor could detect sarcosine down to 7.0 nM with a maximal peak current output at 4.10 ± 0.35 × 10−5 A using only 100 µL of a sample per measurement. The assay run in 100 μL of an electrolyte showed the first linear calibration curve in a concentration window of up to 5 μM with a slope of 2.86 μA·μM−1, and the second linear calibration curve in the range of 5–50 μM with a slope of 0.32 ± 0.01 μA·μM−1 (R2 = 0.992). The device provided a high recovery index of 92.5% when measuring an analyte spiked into artificial urine, and could be used for detection of sarcosine in urine for at least a period of 5 weeks after the preparation.

Sarcosine level in serum is of important clinical significance in distinguishing prostate cancer. This work depicts an amperometric sarcosine biosensor with good anti-interference performance by electro-codepositing manganese phosphate, 3,4-ethylenedioxythiophene (EDOT) and indole-6-carboxylic acid (IA) on the glass carbon electrode. The prepared sarcosine biosensor has a wide linear detection range (1-55 µM) with a low detection limit of 0.11 µM. This work provides an antiinterference approach by controlling the surface charge density of the biosensor to sarcosine sensing, which has great potential to be used as point of care testing (POCT) device for the rapid detection of prostate cancer biomarkers. [ABSTRACT FROM AUTHOR]

The potential of micronutrients to ameliorate the impact of prenatal alcohol exposure (PAE) was explored in a clinical trial conducted in Ukraine. Cardiac orienting responses (ORs) during a habituation/dishabituation learning paradigm were obtained from 6 to 12 month-olds to assess neurophysiological encoding and memory. Women who differed in prenatal alcohol use were recruited during pregnancy and assigned to a group (No study-provided supplements, multivitamin/mineral supplement, or multivitamin/mineral supplement plus choline supplement). Heart rate was collected for 30 s prior to stimulus onset and 12 s post-stimulus onset. Difference values (∆HR) for the first 3 trials of each condition were aggregated for analysis. Gestational blood samples were collected to assess maternal nutritional status and changes as a function of the intervention. Choline supplementation resulted in a greater ∆HR on the visual habituation trials for all infants and for the infants with no PAE on the dishabituation trials. The latency of the response was reduced in both conditions for all infants whose mothers received choline supplementation. Change in gestational choline level was positively related to ∆HR during habituation trials and levels of one choline metabolite, dimethylglycine (DMG), predicted ∆HR during habituation trials and latency of responses. A trend was found between DMG and ∆HR on the dishabituation trials and latency of the response. Supplementation did not affect ORs to auditory stimuli. Choline supplementation when administered together with routinely recommended multivitamin/mineral prenatal supplements during pregnancy may provide a beneficial impact to basic learning mechanisms involved in encoding and memory of environmental events in alcohol-exposed pregnancies as well as non- or low alcohol-exposed pregnancies. Changes in maternal nutrient status suggested that one mechanism by which choline supplementation may positively impact brain development is through prevention of fetal alcohol-related depletion of DMG, a metabolic nutrient that can protect against overproduction of glycine, during critical periods of neurogenesis.

We describe herein an improved amperometric biosensor for detection of sarcosine, a potential biomarker for prostate cancer. The biosensor is based on covalent immobilization of sarcosine oxidase (SOx) onto nanocomposite of chitosan (CHIT) and graphene nanoribbons (GNRs) electrodeposited onto Au electrode. The GNRs were studied by transmission electron microscopy and UV spectroscopy. The working electrode (SOx/CHIT/GNRs/AuE) exhibited maximum current at a potential of 0.1V against Ag/AgCl, generated from electrochemical oxidation of H2O2, from sarcosine by immobilized SOx. The biosensor showed optimum response i.e. current (mA) within 2s at pH 7.3 and 35 ​°C. There was a linearity between current (mA) and sarcosine concentration in a wider range 0.001–100 ​μM with a minimum detection limit of 0.001 ​μM and a high sensitivity of 277.5 ​μA/μM/cm. Analytical recoveries of added sarcosine in sera were 97.35%, within and between-batch coefficients of variation were 1.08% and 1.40% respectively. A good correlation (R² ​= ​0.99) was obtained between sera sarcosine values, as measured by the standard immuno kit method and present biosensor. The biosensor measured sarcosine levels in sera of prostate cancer patients, which was significantly higher than in apparently healthy persons. The enzyme electrode lost 20% of its initial activity during 180days, when stored dry at 4°C. [ABSTRACT FROM AUTHOR]

Sarcosine is one of the known small molecule biomarkers to detect prostate cancer effectively. In the present work, we presented a very simple procedure and low-cost non-enzymatic method for the detection of Sarcosine. Zinc oxide (ZnO) nanoparticles were successfully synthesized, characterized and elucidated the morphology on the Indium tin oxide (ITO) surface, which showed uniform arrangement with a spherical shape. The ITO working electrode modified with ZnO exhibits better analytical characteristics for Sarcosine sensing with a linear range between 5 and 100 nM. The limit of detection was found to be low (7.5 nM) with excellent sensitivity and possess quick response time. Due to its high specificity and repeatability, the ITO/ZnO working electrode does not interfere with the other amino acids in the real samples. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides (AMPs) are potential therapeutic agents against bacteria. We recently showed that a rationally designed AMP, termed Stripe, with an amphipathic distribution of native cationic and hydrophobic amino acids on its helical structure exhibited potent antimicrobial activity against Gram‐positive and Gram‐negative bacteria with negligible hemolytic activity and cytotoxicity. In this study, the structure–activity relationship of Stripe was elucidated by designing a series of antimicrobial peptides whereby amino acid residues of Stripe were exchanged with helix‐destabilizing sarcosine residues. Stripe 1–5 peptides with hydrophobic amino acids substituted with sarcosine were predominantly unstructured and showed no antimicrobial activity, except against Escherichia coli (E. coli) (DH5α) cells. The activity against E. coli (DH5α) cells and the helicity of Stripe 1–5 peptides decreased concomitantly as the number of sarcosine residue substitutions increased. Stripe 1–5 peptides showed no hemolytic activity or cytotoxicity. The results indicate that sarcosine substitutions provide an approach to study the structure–activity relationship of helical AMPs, and the helicity of Stripe is an important feature defining its activity. [ABSTRACT FROM AUTHOR]

This study was carried out for evaluation of the diagnostic performance of different serological assays; buffered acidified plate antigen test (BAPAT), rose bengal plate test (RBPT), immunochroma-tographic assay (ICA), rivanol test (RivT), indirect ELISA using two types of coating antigens (smooth lipopolysaccharide; S-LPS and N-lauroylsarcosine-extracted antigens; SE) and complement fixation test (CFT). Relative sensitivity and specificity of various techniques were estimated. The traditional serological tests failed to distinguish the vaccinated from naturally infected animals. Using iELISA with extracted antigens (SE) as a coating antigen was a more accurate test to differentiate the naturally infected animals from vaccinated animals. Application of restriction fragment length poly-morphism polymerase chain reaction (RFLP-PCR) on sera samples from seropositive animals, Rev-1 vaccinated sheep and Brucella field strain infected sheep and goats revealed that there were samples identified as B. melitensis biovar 3 field strain and other samples identified as B. melitensis Rev-1 vaccinal strain. The obtained results established that restriction fragment length polymorphism-polymerase chain reaction can differentiate between animals infected with Brucella field strains from animals vaccinated with the Rev-1 vaccine.

Accurate determination of Sarcosine (SAR) in urine with high sensitivity and selectivity is important, because it was recently recommended as a prospective biomarker for prostate cancer (PCa) and significant for the early identification of PCa. In this study, an electrochemical sensor based on Fe3O4 incorporated metal–organic frameworks (MOFs) @molecularly imprinted polymer (MIP) was constructed for SAR detection. Magnetic Fe3O4 nanoparticles embedded zeolitic imidazolate framework-8 (ZIF-8) was used as the support of MIP. MIP provides specific recognition sites for template molecules SAR and MOFs increase the rate of mass transfer and adsorption capacity due to the porous structure. The synthesized super-magnetic Fe3O4@ZIF-8@MIP was self-assembled onto an Au electrode in magnetic field and used as the sensing unit of electrochemical sensor. Cyclic voltammetry was used to monitor the electrochemical behavior, and the binding of SAR resulted in a reduction in the measured current. The results revealed a wide linear range from 1 to 100 pM towards trace SAR determination, with extremely low limit of detection down to 0.4 pM. In conclusion, the Fe3O4@ZIF-8@MIP based sensor provides a selective, sensitive, and convenient method for SAR diagnosis and other cancer marker detection.

We describe herein an improved amperometric biosensor for detection of sarcosine, a potential biomarker for prostate cancer. The biosensor is based on covalent immobilization of sarcosine oxidase (SOx) onto nanocomposite of chitosan (CHIT) and graphene nanoribbons (GNRs) electrodeposited onto Au electrode. The GNRs were studied by transmission electron microscopy and UV spectroscopy. The working electrode (SOx/CHIT/GNRs/AuE) exhibited maximum current at a potential of 0.1V against Ag/AgCl, generated from electrochemical oxidation of H2O2, from sarcosine by immobilized SOx. The biosensor showed optimum response i.e. current (mA) within 2s at pH 7.3 and 35 ​°C. There was a linearity between current (mA) and sarcosine concentration in a wider range 0.001–100 ​μM with a minimum detection limit of 0.001 ​μM and a high sensitivity of 277.5 ​μA/μM/cm. Analytical recoveries of added sarcosine in sera were 97.35%, within and between-batch coefficients of variation were 1.08% and 1.40% respectively. A good correlation (R2 ​= ​0.99) was obtained between sera sarcosine values, as measured by the standard immuno kit method and present biosensor. The biosensor measured sarcosine levels in sera of prostate cancer patients, which was significantly higher than in apparently healthy persons. The enzyme electrode lost 20% of its initial activity during 180days, when stored dry at 4°C.

Abstract Background Dendritic cell (DC) vaccine efficacy is directly related to the efficiency of DC migration to the lymph node after delivery to the patient. We discovered that a naturally occurring metabolite, sarcosine, increases DC migration in human and murine cells resulting in significantly improved anti-tumor efficacy. We hypothesized that sarcosine induced cell migration was due to chemokine signaling. Methods DCs were harvested from the bone marrow of wild type C57BL/6 mice and electroporated with tumor messenger RNA (mRNA). Human DCs were isolated from peripheral blood mononuclear cells (PBMCs). DCs were treated with 20 mM of sarcosine. Antigen specific T cells were isolated from transgenic mice and injected intravenously into tumor bearing mice. DC vaccines were delivered via intradermal injection. In vivo migration was evaluated by flow cytometry and immunofluorescence microscopy. Gene expression in RNA was investigated in DCs via RT-PCR and Nanostring. Results Sarcosine significantly increased human and murine DC migration in vitro. In vivo sarcosine-treated DCs had significantly increased migration to both the lymph nodes and spleens after intradermal delivery in mice. Sarcosine-treated DC vaccines resulted in significantly improved tumor control in a B16F10-OVA tumor flank model and improved survival in an intracranial GL261-gp100 glioma model. Gene expression demonstrated an upregulation of CXCR2, CXCL3 and CXCL1 in sarcosine- treated DCs. Further metabolic analysis demonstrated the up-regulation of cyclooxygenase-1 and Pik3cg. Sarcosine induced migration was abrogated by adding the CXCR2 neutralizing antibody in both human and murine DCs. CXCR2 neutralizing antibody also removed the survival benefit of sarcosine-treated DCs in the tumor models. Conclusion Sarcosine increases the migration of murine and human DCs via the CXC chemokine pathway. This platform can be utilized to improve existing DC vaccine strategies.

Glycine transporter 1 (GlyT1) mediates the termination of inhibitory glycinergic receptor signaling in the spinal cord and brainstem, and is also present diffusely in the forebrain. Here, it regulates the ambient glycine concentration and influences the 'glycine' site occupancy of N-methyl-d-aspartate receptors (NMDARs). GlyT1 is a reversible transporter with a substantial, but not excessive, sodium-motive force for uphill transport. This study investigates its role as a potential source of glycine supply, either by reverse uptake or heteroexchange. Indeed, glutamate alone does not induce NMDAR current in "naive" oocytes co-expressing GluN1/GluN2A and GlyT1, a previously characterized cellular model. However, after substantial intracellular glycine accumulation, GlyT1 reverses its transport mode, and begins to release glycine into the external compartment, allowing NMDAR activation by glutamate alone. These uptake-dependent glutamate currents were blocked by ALX-5407 and potentiated by sarcosine, a specific inhibitor and substrate of GlyT1, respectively, suggesting a higher occupancy of the co-agonist site when GlyT1 functions as a glycine source either by reversed-uptake or by heteroexchange. These two glycine release mechanisms can be distinguished by their voltage dependence, as the reversed-uptake cycle decreases at hyperpolarized potentials, whereas heteroexchange electroneutrality preserves glycine efflux and NMDAR activation at these potentials. These results establish GlyT1-mediated efflux as a positive regulator of NMDAR coagonist site occupancy, and demonstrate the efficacy of sarcosine heteroexchange in enhancing coagonist site occupancy. Because NMDAR facilitation by GlyT1-inhibitors and sarcosine relies on different transport mechanisms, their actions may be a source of variability in reversing NMDAR hypofunction in schizophrenia., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The multiplexed detection of metabolites in parallel within a single biosensor plate is sufficiently valuable but also challenging. Herein, we combine the inherent light addressability of silicon with the high selectivity of enzymes, for the construction of multiplexed photoelectrochemical enzymatic biosensors. To conduct a stable electrochemistry and reagentless biosensing on silicon, a new strategy involving the immobilization of both redox mediators and enzymes using an amide bond-based hydrogel membrane was proposed. The membrane characterization results demonstrated a covalent coupling of ferrocene mediator to hydrogel, in which the mediator acted as not only a signal generator but also a renewable sacrifice agent. By adding corresponding enzymes on different spots of hydrogel membrane modified silicon and recording local photocurrents with a moveable light pointer, this biosensor setup was used successfully to detect multiple metabolites, such as lactate, glucose, and sarcosine, with good analytical performances. The limits of detection of glucose, sarcosine and lactate were found to be 179 μM, 16 μM, and 780 μM with the linear ranges of 0.5-2.5 mM, 0.3-1.5 mM, and 1.0-3.0 mM, respectively. We believe this proof-of-concept study provides a simple and rapid one-step immobilization approach for the fabrication of reagentless enzymatic assays with silicon-based light-addressable electrochemistry., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The in vitro diagnostics of cancer are not represented well yet, but the need for early-stage detection is undeniable. In recent decades, surface-enhanced Raman spectroscopy (SERS) has emerged as an efficient, adaptable, and unique technique for the detection of cancer molecules in their early stages. Herein, we demonstrate an opto-plasmonic hybrid structure for sensitive detection of the prostate cancer biomarker sarcosine using silica nanospheres coated silver nano-islands as a facile and efficient SERS active substrate. The SERS active platform has been developed via thin (5–15 nm) deposition of silver islands using a simple and cost-effective Radio Frequency (RF) sputtering technique followed by the synthesis and decoration of silica nanospheres (~500 nm) synthesized via Stober’s method. It is anticipated that the coupling of Whispering Gallery Modes and photonic nano-jets in SiO2 nanospheres induce Localized Surface Plasmon Resonance (LSPR) in Ag nano-islands, which is responsible for the SERS enhancement. The as-fabricated SERS active platform shows a linear response in the physiological range (10 nM to 100 μM) and an extremely low limit of detection (LOD) of 1.76 nM with a correlation coefficient of 0.98 and enhancement factor ~2 × 107. The findings suggest that our fabricated SERS platform could be potentially used for the rapid detection of bio-chemical traces with high sensitivity.

Glycine betaine (GB) is a biologically important compound for microbial communities living in saline habitats most commonly employed as an organic osmolyte. At fluctuating salinity, halophilic microbes producing GB excrete it into environment making it available for heterotrophic/methylotrophic community members as a source of carbon, energy and nitrogen. Although many halolalkaliphilic bacteria have a potential for synthesis of GB as the main osmolyte, so far there was no targeted investigation of its microbial mineralization at soda lake conditions. In this work GB was used as substrate to enrich for GB-utilizing bacteria and archaea from sediments of hypersaline soda lakes located in southwestern Siberia. Aerobic enrichments at moderate and soda-saturated conditions (pH 10) resulted in isolation of several gammaproteobacterial strains identical in its 16S RNA gene to each other and to the known species Halomonas alkalicola. These isolates grew equally well with several methylated compounds: methylglycine (sarcosine), dimethylglycine (DMG), GB and choline (trimethylethanolamine). No growth was observed in aerobic hypersaline enrichments in presence of antibiotics indicating that bacteria are the main mineralizers of GB in hypersaline soda lakes at oxic conditions. In contrast, an anaerobic enrichment at 4 M Na+ and pH 9.7 targeting GB-utilizing haloalrchea was positive with sulfur as electron acceptor and resulted in isolation of a pure natronarchaeal culture belonging to the previously described genus of sulfur-reducing haloarchaea Halalkaliarchaeum. Anaerobic enrichments with GB at fermentative conditions were positive at salinities 2−4 M total Na+ (pH 10) and consisted of a bacterial component forming trimethyamine (TMA) and methylotrophic methanogens consuming the latter. In both cases the bacterial component belonged to the genus Natroniella (Halanaerobiia), while the methanogenic partner at 2 M Na+ was identified as Methanosalsum natronophilum and at 4 M Na+/48°C—as members of the methyl-reducing genus Methanonatronarchaeum. [ABSTRACT FROM AUTHOR]

Objective: Modulation of glutamatergic neurotransmission in schizophrenia by sarcosine leads to a reduction in primary negative symptoms, while its metabolic profile is safe. In order to extend research in the area, we assessed serum levels of neuropeptide Y (NPY), a hypothalamic hormone related to anxiety and depression, also involved in mechanisms inducing weight gain. Additionally, we analyzed associations between NPY concentrations and its changes with severity of symptoms and metabolic parameters. Methods: A prospective 6‐month, randomized, double‐blind placebo‐controlled trial was completed by 57 subjects with chronic schizophrenia with predominant negative symptoms and stable antipsychotic treatment. The participants received 2 g of sarcosine (n = 28) or placebo (n = 29) daily. We assessed serum NPY concentrations and severity of symptoms (with the Positive and Negative Syndrome Scale [PANSS] and Calgary Depression Scale for Schizophrenia) at the beginning of the study, after 6 weeks and 6 months. Results: Sarcosine did not affect NPY levels in all time points. The highest decrease in NPY concentrations was observed in the subjects who were initially depressed, who became euthymic at the last visit. We noticed an improvement in the total PANSS score, and negative symptom and general psychopathology subscales in the sarcosine group, however, without any correlation with NPY levels. Conclusion: The use of sarcosine does not change NPY levels. Peripheral NPY concentrations may be related to depressive symptoms in schizophrenia. [ABSTRACT FROM AUTHOR]

Aminophosphonates, like glyphosate (GS) or metal chelators such as ethylenediaminetetra(methylenephosphonic acid) (EDTMP), are released on a large scale worldwide. Here, we have characterized a bacterial strain capable of degrading synthetic aminophosphonates. The strain was isolated from LC/MS standard solution. Genome sequencing indicated that the strain belongs to the genus Ochrobactrum. Whole-genome classification using pyANI software to compute a pairwise ANI and other metrics between Brucella assemblies and Ochrobactrum contigs revealed that the bacterial strain is designated as Ochrobactrum sp. BTU1. Degradation batch tests with Ochrobactrum sp. BTU1 and the selected aminophosphonates GS, EDTMP, aminomethylphosphonic acid (AMPA), iminodi(methylene-phosphonic) (IDMP) and ethylaminobis(methylenephosphonic) acid (EABMP) showed that the strain can use all phosphonates as sole phosphorus source during phosphorus starvation. The highest growth rate was achieved with AMPA, while EDTMP and GS were least supportive for growth. Proteome analysis revealed that GS degradation is promoted by C-P lyase via the sarcosine pathway, i.e., initial cleavage at the C-P bond. We also identified C-P lyase to be responsible for degradation of EDTMP, EABMP, IDMP and AMPA. However, the identification of the metabolite ethylenediaminetri(methylenephosphonic acid) via LC/MS analysis in the test medium during EDTMP degradation indicates a different initial cleavage step as compared to GS. For EDTMP, it is evident that the initial cleavage occurs at the C-N bond. The detection of different key enzymes at regulated levels, form the bacterial proteoms during EDTMP exposure, further supports this finding. This study illustrates that widely used and structurally more complex aminophosphonates can be degraded by Ochrobactrum sp. BTU1 via the well-known degradation pathways but with different initial cleavage strategy compared to GS. • Bacterial isolate capable of degrading different synthetic aminophosphonates. • Antibiotic susceptibility test shows resistance to only sulphonamide. • In silico analysis confirms the genus of Ochrobactum. • Initial cleavage of GS at C-P bond. • Initial cleavage of EDTMP, AMPA, IDMP and EABMP at C-N bond. [ABSTRACT FROM AUTHOR]

In this study, an electrochemical aptasensor was developed for the specific detection of sarcosine using a covalent organic framework (COF). The imine-based two-dimensional COF was synthesized through a solvothermal process using terephthaldehyde and melamine. This resulted in the formation of a structure that is highly porous and has a unique surface area of 908 m2/g. The produced biosensor demonstrated a significant linear relationship between charge transfer resistance (Rct) and various concentrations of sarcosine in blood serum samples. The aptasensor had two linear ranges, spanning from 0.5 fM to 700 fM and 10 pM to 0.12 nM, respectively, with a detection limit of 0.15 fM. The incorporation of high surface area COFs in the aptasensor design offers a promising combination of sensitivity, stability, and specificity. This combination creates a valuable device for diagnosing and monitoring of prostate cancer and potentially other diseases. [Display omitted] • This aptasensor has the lowest detection limit for the sarcosine determination compared to other reported methods. • The aptasensor illustrates the ultra-sensitivity and selectivity detection for the sarcosine. • Covalent organic framework is used as a sensing interface to design the electrochemical aptasensor. • The application of the aptasensor in spiked serum samples is evaluated. [ABSTRACT FROM AUTHOR]

MXenes are gaining immense attention owing to their robust conductivity, presence of favorable surface-functional groups and excellent hydrophilicity. Herein, a simple solution-based approach was adopted to functionalize few-layer thick MXene-Ti 3 C 2 T x with chitosan (Chi) molecules, creating a stable electro-active screen-printed electrode (SPE) platform for the detection of sarcosine (SAR), a new biomarker for prostate cancer. In comparison to pristine MXene, the chitosan-functionalized Ti 3 C 2 T x (MX-Chi/SPE) offered favorable surface functionalization for easy immobilization of sarcosine oxidase (SO x) enzymes, which led to the improved enzymatic oxidation of SAR. The detection mechanism relied upon the efficient reduction of enzymatically produced H 2 O 2 over MX-Chi/SPE, enabling selective detection of SAR both in low (0.1–0.3 µM) and high (1.5–3.5 µM) concentration ranges, with an estimated limit of detection (LOD) values of 0.012 µM and 0.14 µM (S/N = 3), respectively. Due to its robust enzymatic configuration, the biosensor enabled selective detection of SAR even in the presence of interfering species like ascorbic acid, uric acid, and glucose. Furthermore, the biosensor demonstrated excellent signal repeatability and stability and effectively recovered spiked SAR levels (98–106%) from artificial urine samples. This approach demonstrated the successful integration of MXenes as redox-active materials in clinical biosensors with a simple electrode preparation procedure, which has the potential to be extended to other MXene compositions. • Binder-free MX-Chi anode for sensitive enzymatic biosensing of the SAR biomarker. • Chitosan functionalized Ti 3 C 2 T x for high conductivity and linker-free immobalization of sacrocine oxidase. • Ti 3 C 2 T x and chitosan network creates a robust network with LOD of 0.012 µM for SAR. • MX-Chi Integrated SPE for SAR at low (0.1–0.3 µM) and high (1.5–3.5 µM) concentrations. [ABSTRACT FROM AUTHOR]

DNA hypermethylation is one of the most common epigenetic modifications in prostate cancer (PCa). Several studies have delineated sarcosine as a PCa oncometabolite that increases the migration of malignant prostate cells while decreasing their doubling time. Here, we show that incubation of prostate cells with sarcosine elicited the upregulation of sarcosine N‐demethylation enzymes, sarcosine dehydrogenase and pipecolic acid oxidase. This process was accompanied by a considerable increase in the production of the major methyl‐donor S‐adenosylmethionine (SAMe), together with an elevation of cellular methylation potential. Global DNA methylation analyses revealed increases in methylated CpG islands in distinct prostate cell lines incubated with sarcosine, but not in cells of nonprostate origin. This phenomenon was further associated with marked upregulation of DNA methyltransferases (Dnmts). Epigenetic changes were recapitulated through blunting of Dnmts using the hypomethylating agent 5‐azacytidine, which was able to inhibit sarcosine‐induced migration of prostate cells. Moreover, spatial mapping revealed concomitant increases in sarcosine, SAMe and Dnmt1 in histologically confirmed malignant prostate tissue, but not in adjacent or nonmalignant tissue, which is in line with the obtained in vitro data. In summary, we show here for the first time that sarcosine acts as an epigenetic modifier of prostate cells and that this may contribute to its oncometabolic role.

Abstract To date, there has been no evidence regarding the association between urinary sarcosine content and prostate cancer survival. Our main objective was to investigate whether levels of post‐treatment urinary sarcosine are associated with relapse. The inclusion criteria were (in accordance with EAU 2017) as follows: histopathologically verified adenocarcinoma in prostate biopsy cores or specimens from transurethral resection of the prostate (TURP) or prostatectomy for benign prostatic enlargement (BPE) with retained ability to urinate. The median follow‐up was 53 months. In the study, we retrospectively evaluated a cohort of 511 patients with prostate cancer with various risk factors and treatment strategies. Post‐treatment sarcosine levels were elevated in 266 (52%) patients and highly elevated (≥200 nmol/L) in 71 (13%) patients. Urinary sarcosine content was significantly associated with number of relapses that patients experienced, P = 0.002 for sarcosine ≥200 vs ≤30 nmol/L. Multivariate analysis revealed that sarcosine was an independent predictor of recurrent relapses (≥2 relapses with an intermediate period of remission), HR = 3.89 (95% CI 1.29‐11.7) for sarcosine >200 vs

Sarcosine has been identified as a key metabolite marker for monitoring and early diagnosis of metastatic prostate cancer (PCa), and it is detectable in the urine of patients. In the present study, a carbon past electrode modified with TiO2 nanoparticles in 1-butyl-3-methylimidazolium tetrafluoroborate ionic liquid is proposed for the voltammetric determination of sarcosine in biological samples. Electrochemical impedance spectroscopy was used to study the charge transfer properties of the proposed electrode at the electrode–solution interface. Cyclic and differential pulse voltammetric methods were used to evaluate sarcosine electrochemical behaviour. Electrochemical oxidation of sarcosine on the new TiO2/ionic liquid carbon paste electrode (TiO2/IL/CPE) was carefully studied. The plot of oxidation peak current versus the concentration of sarcosine consists of two separate linear portions. The first part is for 0.1 to 1 mM (direct proportion) and the second one is for 1.0 to 5.0 mM of sarcosine (linear portion). The detection limit was 0.08 mM (3σ) in phosphate buffer (pH 11.5). The measurement and fabrication reproducibilities of the modified sensor were 1.7 and 3.46% for 0.6 mM sarcosine, respectively. The proposed method was successfully applied for the determination of sarcosine in a spiked real sample. [ABSTRACT FROM AUTHOR]

Introduction: Prostate cancer is the second leading cause of cancer-related death in men. In the present study, the expression level of glycine N-methyl transferase gene (GNMT) was investigated in prostate cancer tissue. The GNMT enzyme is encoded by the GNMT gene. Increased GNMT gene expression increases the conversion of glycine to sarcosine and results in the elevated levels of sarcosine in blood and urine. Methods: The expression level of GNMT gene in tissue samples of patients with prostate cancer was compared with those with benign prostatic hyperplasia using Real-Time PCR technique. Results: The GNMT gene expression level increased significantly in prostate cancer patients compared with those with benign prostatic hyperplasia (p-value <0.001). In addition, the expression level of GNMT gene was stage-dependent and significant increases were observed in all stages of prostate cancer compared with those with benign prostatic hyperplasia (p-value <0.001). Conclusion: The concentration of sarcosine is controlled by GNMT and it seems that increasing the expression level of GNMT gene increases the level of sarcosine concentration. Thus, it appears that increased levels of GNMT expression occur in the early stages of prostate cancer. Therefore, periodic measurement of GNMT expression levels can detect prostate cancer before it forms a cancer cell and invades other tissues. [ABSTRACT FROM AUTHOR]

Paracoccus denitrificans is a facultative methylotroph that can grow on methanol and methylamine as sole sources of carbon and energy. Both are oxidized to formaldehyde and then to formate, so growth on C1 substrates induces the expression of genes encoding enzymes required for the oxidation of formaldehyde and formate. This induction involves a histidine kinase response regulator pair (FlhSR) that is likely triggered by formaldehyde. Catabolism of some complex organic substrates (e.g., choline and L-proline betaine) also generates formaldehyde. Thus, flhS and flhR mutants that fail to induce expression of the formaldehyde catabolic enzymes cannot grow on methanol, methylamine, and choline. Choline is oxidized to glycine via glycine betaine, dimethylglycine, and sarcosine. By exploring flhSR growth phenotypes and the activities of a promoter and enzyme known to be upregulated by formaldehyde, we identify the oxidative demethylations of glycine betaine, dimethylglycine, and sarcosine as sources of formaldehyde. Growth on glycine betaine, dimethylglycine, and sarcosine is accompanied by the production of up to three, two, and one equivalents of formaldehyde, respectively. Genetic evidence implicates two orthologous monooxygenases in the oxidation of glycine betaine. Interestingly, one of these appears to be a bifunctional enzyme that also oxidizes L-proline betaine (stachydrine). We present preliminary evidence to suggest that growth on L-proline betaine induces expression of a formaldehyde dehydrogenase distinct from the enzyme induced during growth on other formaldehyde-generating substrates.IMPORTANCEThe bacterial degradation of one-carbon compounds (methanol and methylamine) and some complex multi-carbon compounds (e.g., choline) generates formaldehyde. Formaldehyde is toxic and must be removed, which can be done by oxidation to formate and then to carbon dioxide. These oxidations provide a source of energy; in some species, the CO 2 thus generated can be assimilated into biomass. Using the Gram-negative bacterium Paracoccus denitrificans as the experimental model, we infer that oxidation of choline to glycine generates up to three equivalents of formaldehyde, and we identify the three steps in the catabolic pathway that are responsible. Our work sheds further light on metabolic pathways that are likely important in a variety of environmental contexts., Competing Interests: The authors declare no conflict of interest.

As the well-known test-indicator for early prostate cancer (PCa), sarcosine (SA) is closely related to the differential pathological process, which makes its accurate determination increasingly significant. Herein, we for the first time expanded the peroxidase (POD)-like property of facile-synthesized Zn-TCPP(Fe) MOF to fluorescent substrates and exploited it to ratiometric fluorescent (RF) sensing. By harnessing the effective catalytic oxidation of MOF nanozyme toward two fluorescent substrates (Scopoletin, SC; Amplex Red, AR) with contrary changes, and target-responsive (SA + SOx)/MOF/(SC + AR) tandem catalytic reaction, we constructed the first MOF nanozyme-based RF sensor for the quantitative determination of SA. Superior to previous works, the operation of this RF sensor is under the guidance of AND-(AND^NAND) contrary logic circuit. The dual-channel binary output changes (from 1/0 to 0/1) not only enable the intelligent logical recognition of SA, bringing strengthened reliability and accuracy, but also manifest the proof-of-concept discrimination of PCa individuals and healthy ones. Through recording the fluorescence alterations of SC (F 465 ) and AR (F 585 ), two segments of linear relationships between ratiometric values (F 585 /F 465 ) and varied contents of SA are realized successfully. The LOD for SA could reach to as low as 39.98 nM, which outperforms all nanozyme-originated SA sensors reported till now. Moreover, this sensor also demonstrates high selectivity and satisfactory performance in human serum samples. Furthermore, the portable sensing of SA is realized under the assistance of smartphone-based RGB analysis, demonstrating the potential of point-of-care diagnostics of PCa in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Glyphosate and nitrogen (N) or (P) phosphorus fertilizers are often applied in combination to agricultural fields. The additional P or N supply to microorganisms might drive glyphosate degradation towards sarcosine/glycine or aminomethylphosphonic acid (AMPA), and consequently determine the speciation of non-extractable residues (NERs): harmless biogenic NERs (bioNERs) or potentially hazardous xenobiotic NERs (xenoNERs). We therefore investigated the effect of P or N-fertilizers on microbial degradation of glyphosate and bioNER formation in an agricultural soil. Four different treatments were incubated at 20 °C for 75 days as follows; I: no fertilizer (2- 13 C, 15 N-glyphosate only, control), II: P-fertilizer (superphosphate + 2- 13 C, 15 N-glyphosate, effect of P-supply), III: N-fertilizer (ammonium nitrate + 2- 13 C, 15 N-glyphosate, effect of N-supply) and IV: 15 N-fertilizer ( 15 N-ammonium nitrate + 2- 13 C-glyphosate, differentiation between microbial assimilations of 15 N: 15 N-fertilizer versus 15 N-glyphosate). We quantified 13 C or 15 N in mineralization, extractable residues, NERs and in amino acids (AAs). At the end, mineralization (36-41 % of the 13 C), extractable 2- 13 C, 15 N-glyphosate/2- 13 C-glyphosate (0.42-0.49 %) & 15 N-AMPA (1.2 %), and 13 C/ 15 N-NERs (40-43 % of the 13 C, 40-50 % of the 15 N) were comparable among treatments. Contrastingly, the 15 N-NERs from 15 N-fertlizer amounted to only 6.6 % of the 15 N. Notably, N-fertilizer promoted an incorporation of 13 C/ 15 N from 2- 13 C, 15 N-glyphosate into AAs and thus the formation of 13 C/ 15 N-bioNERs. The 13 C/ 15 N-AAs were as follows: 16-21 % (N-fertilizer) > 11-13 % (control) > 7.2-7.3 % (P-fertilizer) of the initially added isotope. 2- 13 C, 15 N-glyphosate was degraded via the sarcosine/glycine and AMPA simultaneously in all treatments, regardless of the treatment type. The percentage share of bioNERs within the NERs in the N-fertilized soil was highest ( 13 C: 80-82 %, 15 N: 100 %) compared to 53 % ( 13 C & 15 N, control) and to only 30 % ( 13 C & 15 N, P-fertilizer). We thus concluded simultaneous N & glyphosate addition to soils could be beneficial for the environment due to the enhanced bioNER formation, while P & glyphosate application disadvantageous since it promoted xenoNER formation., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Karolina M. Nowak reports financial support was provided by German Research Foundation. Sohaib Aslam reports was provided by Alexander von Humboldt Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Cell-penetrating peptides (CPPs), for example, arginine (Arg) rich peptides, are used for the intracellular delivery of nucleic acids. In this study, oligosarcosine-conjugated Arg-rich peptides were designed as plasmid DNA (pDNA) carriers, and the physicochemical parameters and transfection efficiency of the peptide/pDNA complexes were evaluated. Oligosarcosine with different lengths were conjugated to a base sequence composed of arginine and α-aminoisobutyric acid (Aib) [(Aib-Arg-Arg) 3 ]. Oligosarcosine conjugation inhibited the aggregation of the complexes after mixing with pDNA, shielded the positive charge of the complexes, and provided efficient pDNA transfection in cultured cells. The efficiency of the pDNA transfection was improved by varying the length of the oligosarcosine moiety (10-15 units were optimal). The cellular uptake efficiency and intracellular distribution of pDNA were the same regardless of oligosarcosine conjugation. These results implied that intracellular processes, including the decondensation of pDNA, contributed to the efficiency of the protein expression from pDNA. This study demonstrated the advantages of oligosarcosine conjugation to Arg-rich CPPs and provided valuable insight into the future design of CPPs.

Objective Sarcosine was postulated in 2009 as a biomarker for prostate cancer (PCa). Here, we assess plasma sarcosine as a biomarker that is complementary to prostate-specific antigen (PSA). Methods Plasma sarcosine was measured using gas chromatography-mass spectrometry (GC-MS) in adults classified as noncancerous controls (with benign prostate hyperplasia [BPH], n = 36), with prostatic intraepithelial neoplasia (PIN, n = 16), or with PCa (n = 27). Diagnostic accuracy was assessed using receiver operating characteristic curve analysis. Results Plasma sarcosine levels were higher in the PCa (2.0 µM [1.3–3.3 µM], P <.01) and the PIN (1.9 µM [1.2–6.5 µM], P <.001) groups than in the BPH (0.9 µM [0.6–1.4 µM]) group. Plasma sarcosine had "good" and "very good" discriminative capability to detect PIN (area under the curve [AUC], 0.734) and PCa (AUC, 0.833) versus BPH, respectively. The use of PSA and sarcosine together improved the overall diagnostic accuracy to detect PIN and PCa versus BPH. Conclusion Plasma sarcosine measured by GC-MS had "good" and "very good" classification performance for distinguishing PIN and PCa, respectively, relative to noncancerous patients diagnosed with BPH. [ABSTRACT FROM AUTHOR]

Epileptogenesis is a common consequence of brain insults, however, the prevention or delay of the epileptogenic process remains an important unmet medical challenge. Overexpression of glycine transporter 1 (GlyT1) is proposed as a pathological hallmark in the hippocampus of patients with temporal lobe epilepsy (TLE), and we previously demonstrated in rodent epilepsy models that augmentation of glycine suppressed chronic seizures and altered acute seizure thresholds. In the present study we evaluated the effect of the GlyT1 inhibitor, sarcosine (aka N-methylglycine), on epileptogenesis and also investigated possible mechanisms. We developed a modified rapid kindling model of epileptogenesis in rats combined with seizure score monitoring to evaluate the antiepileptogenic effect of sarcosine. We used immunohistochemistry and Western blot analysis for the evaluation of GlyT1 expression and epigenetic changes of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in the epileptogenic hippocampi of rats, and further evaluated expression changes in enzymes involved in the regulation of DNA methylation, ten-eleven translocation methylcytosine dioxygenase 1 (TET1), DNA-methyltransferase 1 (DNMT1), and DNMT3a. Our results demonstrated: (i) experimental evidence that sarcosine (3 g/kg, i.p. daily) suppressed kindling epileptogenesis in rats; (ii) the sarcosine-induced antiepileptogenic effect was accompanied by a suppressed hippocampal GlyT1 expression as well as a reduction of hippocampal 5mC levels and a corresponding increase in 5hmC; and (iii) sarcosine treatment caused differential expression changes of TET1 and DNMTs. Together, these findings suggest that sarcosine has unprecedented disease-modifying properties in a kindling model of epileptogenesis in rats, which was associated with altered hippocampal DNA methylation. Thus, manipulation of the glycine system is a potential therapeutic approach to attenuate the development of epilepsy.

• Limited biochemical data reported in disorders of sulfur amino acid metabolism. • Biochemical testing is helpful in assessing treatment efficacy in these disorders. • Sarcosine is a sensitive and specific marker of betaine therapy compliance. The homocystinurias, caused by defects of remethylation and cystathionine-beta-synthase (CBS) deficiency, are characterized by elevated homocysteine and abnormal methionine levels. Various treatments, including injectable hydroxycobalamin and oral betaine, aim to reduce homocysteine toxicity and normalize methionine, but only limited biochemical data has been reported assessing biochemical response to treatment. We analyzed laboratory results in 812 plasma samples from 56 patients with remethylation disorders and 67 patients with CBS deficiency. Total plasma homocysteine (tHcys) decreased with therapy, but rarely normalized regardless of treatment, with highest levels seen in CBS (116 ± 79 μmol/L) and MTHFR (102 ± 56 μmol/L) deficiencies. In CBS deficiency, tHcys correlated positively with methionine (rs = 0.51, p < 0.0001) and inversely with cystine (rs = -0.57, p < 0.0001) consistent with a metabolic block downstream of homocysteine. In patients with remethylation disorders, methionine was mostly normal on therapy, and inversely correlated with tHcys (rs = -0.57, p < 0.0001) demonstrating effectiveness of hydroxycobalamin and/or betaine in stimulating tHcys remethylation. Betaine also significantly increased sarcosine from its pre-treatment level on average 19-fold in remethylation disorders and 3-fold in CBS deficiency, with sarcosine > 5 μmol/L being 97% sensitive and 95% specific for betaine therapy. These results show that existing therapies improve sulfur amino acid metabolism without completely normalizing it and that sarcosine can determine compliance to betaine supplementation. [ABSTRACT FROM AUTHOR]

The reaction of pyrrolo[3,2,1-ij]quinoline-1,2-diones with methyl (het)aryl ketones gave the corresponding 1-(het)arylmethylidenepyrroloquinolin-2-ones, and 1,3-dipolar cycloaddition of the latter to azomethine ylide generated from sarcosine and paraformaldehyde afforded 4-acyl-1,4′,4′,6′-tetramethylspiro[pyrrolidine-3,1′-pyrrolo[3,2,1-ij]quinolin]-2′(4′H)-ones. The synthesized compounds were evaluated for inhibitory activity against blood coagulation factors Xa and XIa. [ABSTRACT FROM AUTHOR]

This study was carried out for evaluation of the diagnostic performance of different serological assays; buffered acidified plate antigen test (BAPAT), rose bengal plate test (RBPT), immunochromatographic assay (ICA), rivanol test (RivT), indirect ELISA using two types of coating antigens (smooth lipopolysaccharide; S-LPS and N-lauroylsarcosine-extracted antigens; SE) and complement fixation test (CFT). Relative sensitivity and specificity of various techniques were estimated. The traditional serological tests failed to distinguish the vaccinated from naturally infected animals. Using iELISA with extracted antigens (SE) as a coating antigen was a more accurate test to differentiate the naturally infected animals from vaccinated animals. Application of restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) on sera samples from seropositive animals, Rev-1 vaccinated sheep and Brucella field strain infected sheep and goats revealed that there were samples identified as B. melitensis biovar 3 field strain and other samples identified as B. melitensis Rev-1 vaccinal strain. The obtained results established that restriction fragment length polymorphism-polymerase chain reaction can differentiate between animals infected with Brucella field strains from animals vaccinated with the Rev-1 vaccine. [ABSTRACT FROM AUTHOR]

Accurate determination of Sarcosine (SAR) in urine with high sensitivity and selectivity is important, because it was recently recommended as a prospective biomarker for prostate cancer (PCa) and significant for the early identification of PCa. In this study, an electrochemical sensor based on Fe 3 O 4 incorporated metal–organic frameworks (MOFs) @molecularly imprinted polymer (MIP) was constructed for SAR detection. Magnetic Fe 3 O 4 nanoparticles embedded zeolitic imidazolate framework-8 (ZIF-8) was used as the support of MIP. MIP provides specific recognition sites for template molecules SAR and MOFs increase the rate of mass transfer and adsorption capacity due to the porous structure. The synthesized super-magnetic Fe 3 O 4 @ZIF-8@MIP was self-assembled onto an Au electrode in magnetic field and used as the sensing unit of electrochemical sensor. Cyclic voltammetry was used to monitor the electrochemical behavior, and the binding of SAR resulted in a reduction in the measured current. The results revealed a wide linear range from 1 to 100 pM towards trace SAR determination, with extremely low limit of detection down to 0.4 pM. In conclusion, the Fe 3 O 4 @ZIF-8@MIP based sensor provides a selective, sensitive, and convenient method for SAR diagnosis and other cancer marker detection. [ABSTRACT FROM AUTHOR]

Epileptogenesis is a common consequence of brain insults, however, the prevention or delay of the epileptogenic process remains an important unmet medical challenge. Overexpression of glycine transporter 1 (GlyT1) is proposed as a pathological hallmark in the hippocampus of patients with temporal lobe epilepsy (TLE), and we previously demonstrated in rodent epilepsy models that augmentation of glycine suppressed chronic seizures and altered acute seizure thresholds. In the present study we evaluated the effect of the GlyT1 inhibitor, sarcosine (aka N-methylglycine), on epileptogenesis and also investigated possible mechanisms. We developed a modified rapid kindling model of epileptogenesis in rats combined with seizure score monitoring to evaluate the antiepileptogenic effect of sarcosine. We used immunohistochemistry and Western blot analysis for the evaluation of GlyT1 expression and epigenetic changes of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in the epileptogenic hippocampi of rats, and further evaluated expression changes in enzymes involved in the regulation of DNA methylation, ten-eleven translocation methylcytosine dioxygenase 1 (TET1), DNA-methyltransferase 1 (DNMT1), and DNMT3a. Our results demonstrated: (i) experimental evidence that sarcosine (3 g/kg, i.p. daily) suppressed kindling epileptogenesis in rats; (ii) the sarcosine-induced antiepileptogenic effect was accompanied by a suppressed hippocampal GlyT1 expression as well as a reduction of hippocampal 5mC levels and a corresponding increase in 5hmC; and (iii) sarcosine treatment caused differential expression changes of TET1 and DNMTs. Together, these findings suggest that sarcosine has unprecedented disease-modifying properties in a kindling model of epileptogenesis in rats, which was associated with altered hippocampal DNA methylation. Thus, manipulation of the glycine system is a potential therapeutic approach to attenuate the development of epilepsy. [ABSTRACT FROM AUTHOR]

Background: Sarcosine (N-methylglycine), a type 1 glycine transporter inhibitor (GlyT1), has shown therapeutic potential for treating schizophrenia; however, studies have reported conflicting results. This meta-analysis aimed to explore the efficacy and cognitive effect of sarcosine for schizophrenia.Methods: In this study, PubMed, Cochrane Systematic Reviews, and Cochrane Collaboration Central Register of Controlled Clinical Trials were searched electronically for double-blinded randomised controlled trials that used sarcosine for treating schizophrenia. We used the published trials up to November 2019 to investigate the efficacy of sarcosine in schizophrenia. We pooled studies by using a random-effect model for comparing sarcosine treatment effects. Patients who were diagnosed with schizophrenia according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition were recruited. Clinical improvement and cognitive function scores between baseline and after sarcosine use were compared using the standardised mean difference (SMD) with 95% confidence intervals (CIs). The heterogeneity of the included trials was evaluated through visual inspection of funnel plots and through the I2 statistic.Results: We identified seven trials with 326 participants with schizophrenia meeting the inclusion criteria. All these studies evaluated the overall clinical symptoms, and four of them evaluated overall cognitive functions. Sarcosine use achieved more significant effects than the use of its comparators in relieving overall clinical symptoms (SMD = 0.51, CI = 0.26-0.76, p < 0.01). Moreover, studies with the low Positive and Negative Syndrome Scale range of 70-79 showed significant effect size (ES)s of 0.67 (95% CI: 0.03-1.31, p = 0.04). In addition, trials enrolling patients with stable clinical symptoms had significant ESs: 0.53 (95% CI: 0.21-0.85, p < 0.01). Add-on sarcosine combined with first- and second-generation antipsychotics, except clozapine, had a positive effect. For overall cognitive functions, sarcosine showed a positive but insignificant effect compared with its comparators (SMD = 0.27, CI = -0.06 to 0.60, p = 0.10). The effects were correlated with increased female proportions and decreased illness duration, albeit nonsignificantly.Conclusions: The meta-analysis suggests that sarcosine may be associated with treatment effect on overall clinical symptoms in patients with schizophrenia but not cognitive functions. [ABSTRACT FROM AUTHOR]

The synthesis of catechol polymers often demands tedious protection and deprotection steps. In this work, the role of a guanidine base to subdue the catechol functions and promote the ring-opening polymerization (ROP) is suggested. Accordingly, guanidine, 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD), was employed to mediate ROP of N-carboxyanhydride (NCA) from a catechol initiator. MTBD played a dual-role in ROP of sarcosine-NCA (Sar-NCA) and masking the catechol initiator concurrently. Catechol-ended polysarcosine (PSar) was synthesized with a predicted molecular weight (Mn,SEC = 3.5 kg mol−1, Mn,NMR = 3.7 kg mol−1) and narrow dispersities (Đ < 1.11). This one base two-function strategy showed a new path for the synthesis of catechol functionalized polymers. [ABSTRACT FROM AUTHOR]

A series of spirooxindoles have been synthesized through 1,3-dipolar cycloaddition of an azomethine ylide generated from isatin and sarcosine or L-proline with the dipolarophile (E)-3-(2-cyclopropyl-5-(4-fluorophenyl) quinolin-3-yl)-1-phenylprop-2-en-1-one derivatives. The stereochemistry of the cycloadducts was assigned based on the single-crystal X-ray. [ABSTRACT FROM AUTHOR]

Purpose: Alcohol consumption is an established breast cancer risk factor, though further research is needed to advance our understanding of the mechanism underlying the association. We used global metabolomics profiling to identify serum metabolites and metabolic pathways that could potentially mediate the alcohol-breast cancer association.Methods: A cross-sectional analysis of reported alcohol consumption and serum metabolite concentrations was conducted among 211 healthy women 25-29 years old who participated in the Dietary Intervention Study in Children 2006 Follow-Up Study (DISC06). Alcohol-metabolite associations were evaluated using multivariable linear mixed-effects regression.Results: Alcohol was significantly (FDR p < 0.05) associated with several serum metabolites after adjustment for diet composition and other potential confounders. The amino acid sarcosine, the omega-3 fatty acid eicosapentaenoate, and the steroid 4-androsten-3beta,17beta-diol monosulfate were positively associated with alcohol intake, while the gamma-tocopherol metabolite gamma-carboxyethyl hydroxychroman (CEHC) was inversely associated. Positive associations of alcohol with 2-methylcitrate and 4-androsten-3beta,17beta-diol disulfate were borderline significant (FDR p < 0.10). Metabolite set enrichment analysis identified steroids and the glycine pathway as having more members associated with alcohol consumption than expected by chance.Conclusions: Most of the metabolites associated with alcohol in the current analysis participate in pathways hypothesized to mediate the alcohol-breast cancer association including hormonal, one-carbon metabolism, and oxidative stress pathways, but they could also affect risk via alternative pathways. Independent replication of alcohol-metabolite associations and prospective evaluation of confirmed associations with breast cancer risk are needed. [ABSTRACT FROM AUTHOR]

A new series of regioselective dispiropyrrolidine analogs via efficient one-pot four-component tandem reaction has been discovered. The reaction was carried out in the presence of four common reactants and magnesium silicate nanoparticles (NPs) in ethanol under microwave irradiation. The reaction proceeds rapidly and can be completed within 60–90 min. This methodology offers several significant advantages such as high yield, mild catalyst, and easy to perform. The synthesized compound was further screened for antibacterial and antiproliferative activities. The results showed that compound 5c and 5a were potent antibacterials against Gram-positive and Gram-negative bacteria. Further, 5a showed best antiproliferative activity against tested cell lines. [ABSTRACT FROM AUTHOR]

Employment of metal nanoparticles has been one of the most promising synthetic strategies for a number of chemical transformations. New spiroindane‐1,3‐diones were synthesized through [3 + 2] cycloaddition in moderate to high yields by a three‐component reaction of heterocyclic chalcone derivatives, ninhydrin, and sarcosine/L‐proline. The presence of heterogenous MgSiO3 nanoparticles (NPs) under microwave irradiation showed a robust effect in improving the yield of the desired products. Furthermore, the catalyst may be recovered and reused without significant loss of activity. [ABSTRACT FROM AUTHOR]